| 1. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Heydarkhan-Hagvall, Sepideh, 1969, et al.
(författare)
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DNA microarray study on gene expression profiles in co-cultured endothelial and smooth muscle cells in response to 4- and 24-h shear stress
- 2006
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Ingår i: Molecular and cellular biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 281:1-2, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Shear stress, a major hemodynamic force acting on the vessel wall, plays an important role in physiological processes such as cell growth, differentiation, remodelling, metabolism, morphology, and gene expression. We investigated the effect of shear stress on gene expression profiles in co-cultured vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Human aortic ECs were cultured as a confluent monolayer on top of confluent human aortic SMCs, and the EC side of the co-culture was exposed to a laminar shear stress of 12 dyn/cm(2) for 4 or 24 h. After shearing, the ECs and SMCs were separated and RNA was extracted from the cells. The RNA samples were labelled and hybridized with cDNA array slides that contained 8694 genes. Statistical analysis showed that shear stress caused the differential expression (p < or = 0.05) of a total of 1151 genes in ECs and SMCs. In the co-cultured ECs, shear stress caused the up-regulation of 403 genes and down-regulation of 470. In the co-cultured SMCs, shear stress caused the up-regulation of 152 genes and down-regulation of 126 genes. These results provide new information on the gene expression profile and its potential functional consequences in co-cultured ECs and SMCs exposed to a physiological level of laminar shear stress. Although the effects of shear stress on gene expression in monocultured and co-cultured EC are generally similar, the response of some genes to shear stress is opposite between these two types of culture (e.g., ICAM-1 is up-regulated in monoculture and down-regulated in co-culture), which strongly indicates that EC-SMC interactions affect EC responses to shear stress.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Akerblad, P, et al.
(författare)
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Gene expression analysis suggests that EBF-1 and PPAR gamma 2 induce adipogenesis of NIH-3T3 cells with similar efficiency and kinetics
- 2005
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 23:2, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation of multipotent mesenchymal stem cells into lipid-accumulating adipocytes is a physiological process induced by transcription factors in combination with hormonal stimulation. We have used Affymetrix microarrays to compare the adipogenic differentiation pathways of NIH-3T3 fibroblasts induced to undergo in vitro differentiation by ectopic expression of early B cell factor (EBF)-1 or peroxisome proliferator-activated receptor (PPAR)gamma 2. These experiments revealed that commitment to the adipogenic pathway in the NIH-3T3 cells was not reflected in gene expression until 4 days after induction of differentiation. Furthermore, gene expression patterns at the earlier time points after stimulation indicated that EBF-1 and PPAR gamma 2 induced different sets of genes, while the similarities increased upon differentiation, and that several genes linked to adipocyte differentiation were also transiently induced in the vector-transduced cells. These data suggest that the initial activation of genes associated with adipocyte development is independent of commitment to the adipogenic pathway and that EBF-1 and PPAR gamma 2 induce adipocyte differentiation with comparable kinetics and efficiency.
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| 7. |
- Barretina, Jordi, et al.
(författare)
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Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 715-21
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Tidskriftsartikel (refereegranskat)abstract
- Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States, show remarkable histologic diversity, with more than 50 recognized subtypes. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.
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| 8. |
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| 9. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 10. |
- Nissen, S, et al.
(författare)
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High-resolution infrared study of the nu(11) band of allene
- 2002
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Ingår i: Journal of Molecular Spectroscopy. - : Elsevier BV. - 0022-2852. ; 216:2, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- The high-resolution infrared spectrum of allene has been observed in the 280-380 cm(-1) region at a nominal resolution of 0.00125 cm(-1) using the IR beamline at the MAX-1 electron storage ring in Lund. The spectrum shows the bending fundamental of the nu(11) band from which spectroscopic constants for the nu(11) level have been obtained. The accompanying hot band component 2nu(11)(2)-nu(11)(1) has also been assigned and analyzed.
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| 11. |
- Andersson, Åke, et al.
(författare)
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Coherent synchrotron radiation in the far infrared from a 1-mm electron bunch
- 2000
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Ingår i: Optical Engineering. - : SPIE-Intl Soc Optical Eng. - 0091-3286. ; 39:12, s. 3099-3105
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Tidskriftsartikel (refereegranskat)abstract
- The coherent generation of synchrotron radiation by an electron storage ring is predicted for wavelengths equal to or longer than the electron bunch length. With typical bunch lengths of approximately 1 cm, diffraction and chamber-screening effects have so far blocked observation of coherent radiation from a conventional radiation beamline. In the low-energy, second-generation light source MAX-I, the magnet lattice has been tuned to a small momentum compaction factor, allowing rms bunch lengths as short as 1 mm. Here we report the coherent far-infrared emission observed from such a bunch. The paper discusses the origin of coherent synchrotron radiation for Gaussian and non-Gaussian electron bunches, and the procedure used to generate such bunches. The emission was characterized using the infrared beamline at MAX-I, including an interferometer, a liquid-helium-cooled bolometer detector, waveguide high-pass filters, and a conductive-grid polarization filter. The intensity of the coherent radiation is greater by a factor of 2×103 to 6×103 than normal incoherent synchrotron radiation, and is seen between 8 and 22 cm-1.
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| 12. |
- Andersson, Åke, et al.
(författare)
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Observation of coherent synchrotron radiation from a 1 mm electron bunch at the MAX-I storage ring
- 1999
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 1996-756X. ; 3775, s. 77-87
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Tidskriftsartikel (refereegranskat)abstract
- The coherent generation of synchrotron radiation by an electron storage ring is predicted for wavelengths equal to or longer than the electron bunch length. With typical bunch lengths of approximately 1 cm, diffraction and chamber- screening effects have so-far blocked observation of coherent radiation from a conventional radiation beam line. In the low-energy, second-generation light source MAX-I, the magnet lattice has been tuned to a small momentum compaction factor, allowing rms bunch lengths as short as 1 mm. Here we report the coherent emission phenomena observed from such a bunch at the infrared beam line attached to the MAX-I ring.The coherent generation of synchrotron radiation by an electron storage ring is predicted for wavelengths equal to or longer than the electron bunch length. With typical bunch lengths of approximately 1 cm, diffraction and chamber- screening effects have so-far blocked observation of coherent radiation from a conventional radiation beam line. In the low-energy, second-generation light source MAX-I, the magnet lattice has been tuned to a small momentum compaction factor, allowing rms bunch lengths as short as 1 mm. Here we report the coherent emission phenomena observed from such a bunch at the infrared beam line attached to the MAX-I ring.
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| 13. |
- Cvijovic, Marija, 1977, et al.
(författare)
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Bridging the gaps in systems biology
- 2014
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Ingår i: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 289:5, s. 727-734
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Tidskriftsartikel (refereegranskat)abstract
- Systems biology aims at creating mathematical models, i.e., computational reconstructions of biological systems and processes that will result in a new level of understanding-the elucidation of the basic and presumably conserved "design" and "engineering" principles of biomolecular systems. Thus, systems biology will move biology from a phenomenological to a predictive science. Mathematical modeling of biological networks and processes has already greatly improved our understanding of many cellular processes. However, given the massive amount of qualitative and quantitative data currently produced and number of burning questions in health care and biotechnology needed to be solved is still in its early phases. The field requires novel approaches for abstraction, for modeling bioprocesses that follow different biochemical and biophysical rules, and for combining different modules into larger models that still allow realistic simulation with the computational power available today. We have identified and discussed currently most prominent problems in systems biology: (1) how to bridge different scales of modeling abstraction, (2) how to bridge the gap between topological and mechanistic modeling, and (3) how to bridge the wet and dry laboratory gap. The future success of systems biology largely depends on bridging the recognized gaps.
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| 14. |
- Fedele, Vita, et al.
(författare)
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Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
- 2017
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Ingår i: Molecular Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1541-7786 .- 1557-3125. ; 15:8, s. 998-1011
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. These results indicate that ZBTB18 functions as a tumor suppressor in GBM through the regulation of genes associated with phenotypically aggressive properties.
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| 15. |
- Giuliani, G., et al.
(författare)
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Round-Robin Measurements of Linewidth Enhancement Factor of Semiconductor Lasers in COST 288 Action
- 2007
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Ingår i: Lasers and Electro-Optics, 2007 and the International Quantum Electronics Conference. CLEOE-IQEC 2007. European Conference on. - 1424409306 - 9781424409303 ; , s. 4385967-
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Konferensbidrag (refereegranskat)abstract
- Round-robin measurements on the linewidth enhancement factor are carried out in many laboratories participating to EU COST 288 Action. Up to 7 different techniques are applied to DFB, VCSELs, QCL, and QD lasers, and results are compared.
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| 16. |
- Goodrose-Flores, C, et al.
(författare)
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High-protein compared with standard parenteral nutrition in palliative cancer care
- 2022
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Ingår i: BMJ supportive & palliative care. - : BMJ. - 2045-4368 .- 2045-435X. ; 12:3, s. 332-338
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Tidskriftsartikel (refereegranskat)abstract
- High-protein parenteral nutrition (PN) has been developed to counteract muscle loss in patients with cancer treated with PN. Nevertheless, it is not clear if high-protein PN is as safe as standard PN in patients with palliative cancer. Our primary aim was to compare the proportion of patients with elevated liver enzymes between high-protein and standard PN in patients with palliative cancer enrolled to Medical Home Care. Our secondary aim was to compare the two treatments with regard to weight and albumin levels during treatment.MethodsMedical records from 2016 to 2018 were retrospectively reviewed to identify palliative cancer patients that had received PN for more than 3 weeks. Data on weight, height, albumin, liver enzymes, socioeconomic factors and dietitian consultations were collected at baseline and after 3–8 weeks of PN treatment. The odds of having elevated liver enzymes or having a maintained weight and/or stable albumin levels were calculated using logistic regression.Results20 patients treated with high-protein PN were compared with 104 patients treated with standard PN. Patients treated with high-protein PN had a significantly higher weight at follow-up compared with patients treated with standard PN (p<0.05). There was no significant difference in the proportion of patients with elevated liver enzymes (OR 0.20; 95% CI 0.02 to 1.86), or maintained weight and/or albumin levels (OR 1.62; 95% CI 0.46 to 5.76) between high-protein and standard PN.ConclusionHigh-protein PN was as safe, and at least as effective, as standard PN to patients with palliative cancer.
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| 17. |
- Heiland, Dieter H., et al.
(författare)
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c-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:4, s. 6940-6954
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Tidskriftsartikel (refereegranskat)abstract
- High-grade gliomas (HGG) are the most common brain tumors, with an average survival time of 14 months. A glioma-CpG island methylator phenotype (G-CIMP), associated with better clinical outcome, has been described in low and high-grade gliomas. Mutation of IDH1 is known to drive the G-CIMP status. In some cases, however, the hypermethylation phenotype is independent of IDH1 mutation, suggesting the involvement of other mechanisms. Here, we demonstrate that DNMT1 expression is higher in low-grade gliomas compared to glioblastomas and correlates with phosphorylated c-Jun. We show that phospho-c-Jun binds to the DNMT1 promoter and causes DNA hypermethylation. Phospho-c-Jun activation by Anisomycin treatment in primary glioblastoma-derived cells attenuates the aggressive features of mesenchymal glioblastomas and leads to promoter methylation and downregulation of key mesenchymal genes (CD44, MMP9 and CHI3L1). Our findings suggest that phospho-c-Jun activates an important regulatory mechanism to control DNMT1 expression and regulate global DNA methylation in Glioblastoma.
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| 18. |
- Hoban, Deirdre B, et al.
(författare)
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Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:26, s. 15209-15220
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better recapitulates the main disease features, obtained by coinjection of preformed human α-synuclein (α-syn) fibrils and adeno-associated virus (AAV) expressing human wild-type α-syn unilaterally into the rat substantia nigra (SN). This model gives rise to DA neuron dysfunction and progressive loss of DA neurons from the SN and terminals in the striatum, accompanied by extensive α-syn pathology and a prominent inflammatory response, making it an interesting and relevant model in which to examine long-term function and integrity of transplanted neurons in a PD-like brain. We transplanted DA neurons derived from human embryonic stem cells (hESCs) into the striatum and assessed their survival, growth, and function over 6 to 18 wk. We show that the transplanted cells, even in the presence of ongoing pathology, are capable of innervating the DA-depleted striatum. However, on closer examination of the grafts, we found evidence of α-syn pathology in the form of inclusions of phosphorylated α-syn in a small fraction of the grafted DA neurons, indicating host-to-graft transfer of α-syn pathology, a phenomenon that has previously been observed in PD patients receiving fetal tissue grafts but has not been possible to demonstrate and study in toxin-based animal models.
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| 19. |
- Kling, Teresia, 1985, et al.
(författare)
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Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma
- 2016
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 12, s. 72-85
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2) as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell-like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 20. |
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| 21. |
- Lund, Lars H, et al.
(författare)
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Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.
- 2023
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Ingår i: European journal of heart failure. - 1879-0844.
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Tidskriftsartikel (refereegranskat)abstract
- Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF.In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo.ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Nelander, Maria, et al.
(författare)
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Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older : a cohort study
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population.DESIGN: Cohort study.SETTING: Sweden.POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion.METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking.MAIN OUTCOME MEASURES: Dementia, CVD, stroke.RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81).CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.
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| 26. |
- Nelander, Rikard, et al.
(författare)
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Fingerprints of spatial charge transfer in Quantum Cascade Lasers
- 2007
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 102, s. 1-113104
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Tidskriftsartikel (refereegranskat)abstract
- We show that mid-infrared transmission spectroscopy of a quantum cascade laser provides clear-cut information on changes in charge location at different bias. Theoretical simulations of the evolution of the gain/absorption spectrum for a lambda~7.4 µm InGaAs/AlInAs/InP quantum cascade laser have been compared with the experimental findings. Transfer of electrons between the ground states in the active region and the states in the injector goes hand in hand with a decrease of discrete intersubband absorption peaks and an increase of broad, high-energy absorption toward the continuum delocalized states above the barriers.
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| 27. |
- Pereira, M. F., Jr., et al.
(författare)
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Characterization of intersubband devices combining a nonequilibrium many body theory with transmission spectroscopy experiments
- 2007
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Ingår i: Journal of Materials Science: Materials in Electronics. - : Springer Science and Business Media LLC. - 0957-4522 .- 1573-482X. ; 18:7, s. 689-694
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we apply a microscopic nonequilibrium many body Keldysh Green's functions approach to an analysis of complex intersubband optical materials and devices. The calculated absorption/gain spectra are in very good agreement with transmission spectroscopy measurements of quantum cascade laser structures operating in the mid-infrared (midIR). The very good agreement reached between theoretical results and experimental measurements benchmarks the predictive power of our algorithms and its potential as a design tool for efficient intersubband designs.
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| 28. |
- Revin, D.G., et al.
(författare)
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Probing the electronic and optical properties of quantum cascade lasers under operating conditions
- 2006
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. ; 6386, s. 1-63860
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We report the realisation of spectroscopic broadband transmission experiments on quantum cascade lasers (QCLs) under continuous wave operating conditions for drive currents up to laser threshold. This technique allows, for the first time, spectroscopic study of light transmission through the waveguide of QCLs in a very broad spectral range (λ~1.5-12 μm), limited only by the detector response and by interband absorption in the materials used in the QCL cladding regions. Waveguide transmittance spectra have been studied for both TE and TM polarization, for InGaAs/InAlAs/InP QCLs with different active region designs emitting at 7.4 and 10μm. The transmission measurements clearly show the depopulation of the lower laser levels as bias is increased, the onset and growth of optical amplification at the energy corresponding to the laser transitions as current is increased towards threshold, and the thermal filling of the second laser level and decrease of material gain at high temperatures. This technique also allows direct determination of key parameters such as the exact temperature of the laser core region under operating conditions, as well as the modal gain and waveguide loss coefficients.
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| 29. |
- Schmidt, Linnéa, et al.
(författare)
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Case-specific potentiation of glioblastoma drugs by pterostilbene
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 73200-73215
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.
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| 30. |
- Schultz, Nikolaus, et al.
(författare)
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Off-target effects dominate a large-scale RNAi screen for modulators of the TGF-beta pathway and reveal microRNA regulation of TGFBR2
- 2011
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Ingår i: Silence. - 1758-907X. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background RNA interference (RNAi) screens have been used to identify novel components of signal-transduction pathways in a variety of organisms. We performed a small interfering (si)RNA screen for novel members of the transforming growth factor (TGF)-β pathway in a human keratinocyte cell line. The TGF-β pathway is integral to mammalian cell proliferation and survival, and aberrant TGF-β responses have been strongly implicated in cancer. Results We assayed how strongly single siRNAs targeting each of 6,000 genes affect the nuclear translocation of a green fluorescent protein (GFP)-SMAD2 reporter fusion protein. Surprisingly, we found no novel TGF-β pathway members, but we did find dominant off-target effects. All siRNA hits, whatever their intended direct target, reduced the mRNA levels of two known upstream pathway components, the TGF-β receptors 1 and 2 (TGFBR1 and TGFBR2), via micro (mi)RNA-like off-target effects. The scale of these off-target effects was remarkable, with at least 1% of the sequences in the unbiased siRNA library having measurable off-target effects on one of these two genes. It seems that relatively minor reductions of message levels via off-target effects can have dominant effects on an assay, if the pathway output is very dose-sensitive to levels of particular pathway components. In search of mechanistic details, we identified multiple miRNA-like sequence characteristics that correlated with the off-target effects. Based on these results, we identified miR-20a, miR-34a and miR-373 as miRNAs that inhibit TGFBR2 expression. Conclusions Our findings point to potential improvements for miRNA/siRNA target prediction methods, and suggest that the type II TGF-β receptor is regulated by multiple miRNAs. We also conclude that the risk of obtaining misleading results in siRNA screens using large libraries with single-assay readout is substantial. Control and rescue experiments are essential in the interpretation of such screens, and improvements to the methods to reduce or predict RNAi off-target effects would be beneficial.
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- Söderlund, Fredrik, et al.
(författare)
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In vitro anti-platelet potency of ticagrelor in blood samples from infants and children.
- 2015
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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 136:3, s. 620-4
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Tidskriftsartikel (refereegranskat)abstract
- Ticagrelor, a novel platelet inhibitor acting on the ADP-dependent P2Y12 receptor, is currently approved for treating adults with acute coronary syndrome. The effect of ticagrelor in children has not been explored. As a first step, we here evaluate if the in vitro anti-platelet potency of ticagrelor in blood samples from children of different age is different as compared with in blood samples from adults.
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