| 61. |
- Ekeberg, Tomas, 1983-, et al.
(författare)
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Three-dimensional structure determination with an X-ray laser
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Three-dimensional structure determination of a non-crystalline virus has been achieved from a set of randomly oriented continuous diffraction patterns captured with an X-ray laser. Intense, ultra-short X-ray pulses intercepted a beam of single mimivirus particles, producing single particle X-ray diffraction patterns that are assembled into a three-dimensional amplitude distribution based on statistical consistency. Phases are directly retrieved from the assembled Fourier distribution to synthesize a three-dimensional image. The resulting electron density reveals a pseudo-icosahedral asymmetric virion structure with a compartmentalized interior, within which the DNA genome occupies only about a fifth of the volume enclosed by the capsid. Additional electron microscopy data indicate the genome has a chromatin-like fiber structure that has not previously been observed in a virus.
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| 62. |
- El-Heliebi, Amin, et al.
(författare)
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In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells
- 2018
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:3, s. 536-546
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wildtype (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.
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| 63. |
- Fedina, Tatiana, et al.
(författare)
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Laser-assisted reduction of iron ore using aluminum powder
- 2023
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Ingår i: Journal of laser applications. - : American Institute of Physics (AIP). - 1042-346X .- 1938-1387. ; 35:2
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Tidskriftsartikel (refereegranskat)abstract
- This study reports on the laser-assisted reduction of iron ore waste using Al powder as areducing agent. Due to climate change and the global warming situation, it has become ofparamount importance to search for and/or develop green and sustainable processes for ironand steel production. In this regard, a new method for iron ore utilization is proposed in thiswork, investigating the possibility of iron ore waste reduction via metallothermic reaction withAl powder. Laser processing of iron ore fines was performed, focusing on the Fe2O3-Alinteraction behavior and extent of the iron ore reduction. The reaction between the materialsproceeded in a rather intense uncontrolled manner which led to a formation of Fe-rich domainsand alumina as two separate phases. In addition, a combination of Al2O3 and Fe2O3 melts aswell as transitional areas such as intermetallics were observed, suggesting the occurrence ofincomplete reduction reaction in isolated regions. The reduced iron droplets were prone toacquire a sphere-like shape and concentrated mainly near the surface of the Al2O3 melt or at theinterface with the iron oxide. Both SEM, EDS and WDS analyses were employed to analyzechemical composition, microstructure and morphological appearances of the reaction products.High-speed imaging was used to study the process phenomena and observe differences in themovement behavior of the particles. Furthermore, the measurements acquired from X-raycomputed microtomography revealed that approximately 2.4 % of iron was reduced during thelaser processing of Fe2O3-Al powder bed, most likely due to insufficient reaction time orinappropriate equivalence ratio of the two components.
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| 64. |
- Feiler, Ute, et al.
(författare)
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Inter-laboratory trial of a standardized sediment contact test with the aquatic plant Myriophyllum aquaticum (ISO 16191)
- 2014
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 33:3, s. 662-670
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Tidskriftsartikel (refereegranskat)abstract
- A whole-sediment toxicity test with Myriophyllum aquaticum has been developed by the German Federal Institute of Hydrology and standardized within the International Organization for Standardization (ISO; ISO 16191). An international ring-test was performed to evaluate the precision of the test method. Four sediments (artificial, natural) were tested. Test duration was 10 d, and test endpoint was inhibition of growth rate (r) based on fresh weight data. Eighteen of 21 laboratories met the validity criterion of r >= 0.09 d(-1) in the control. Results from 4 tests that did not conform to test-performance criteria were excluded from statistical evaluation. The inter-laboratory variability of growth rates (20.6%-25.0%) and inhibition (26.6%-39.9%) was comparable with the variability of other standardized bioassays. The mean test-internal variability of the controls was low (7% [control], 9.7% [solvent control]), yielding a high discriminatory power of the given test design (median minimum detectable differences [MDD] 13% to 15%). To ensure these MDDs, an additional validity criterion of CV <= 15% of the growth rate in the controls was recommended. As a positive control, 90 mg 3,5-dichlorophenol/kg sediment dry mass was tested. The range of the expected growth inhibition was proposed to be 35 +/- 15%. The ring test results demonstrated the reliability of the ISO 16191 toxicity test and its suitability as a tool to assess the toxicity of sediment and dredged material. Environ Toxicol Chem 2014;33:662-670. (c) 2013 SETAC
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| 65. |
- Fischer, Katrin, et al.
(författare)
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Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:5, s. 623-630
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta 3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1(-/-) and interleukin-4 receptor-alpha double-negative (Il4ra(-/-)) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.
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| 66. |
- Fock, J., et al.
(författare)
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Field-dependent dynamic responses from dilute magnetic nanoparticle dispersions
- 2018
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 10:4, s. 2052-2066
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Tidskriftsartikel (refereegranskat)abstract
- The response of magnetic nanoparticles (MNPs) to an oscillating magnetic field outside the linear response region is important for several applications including magnetic hyperthermia, magnetic resonance imaging and biodetection. The size and magnetic moment are two critical parameters for the performance of a colloidal MNP dispersion. We present and demonstrate the use of optomagnetic (OM) and AC susceptibility (ACS) measurements vs. frequency and magnetic field strength to obtain the size and magnetic moment distributions including the correlation between the distributions. The correlation between the size and the magnetic moment contains information on the morphology and intrinsic structure of the particle. In OM measurements, the variation of the second harmonic light transmission through a dispersion of MNPs is measured in response to an oscillating magnetic field. We solve the Fokker-Planck equations for MNPs with a permanent magnetic moment, and develop analytical approximations to the ACS and the OM signals that also account for the change in the curve shapes with increasing field strength. Further, we describe the influence of induced magnetic moments on the signals, by solving the Fokker-Planck equation for particles, which apart from the permanent magnetic moment may also have an induced magnetic moment and shape anisotropy. Using the results from the Fokker-Planck calculations we fit ACS and OM measurements on two multi-core particle systems. The obtained fit parameters also describe the correlations between the magnetic moment and size of the particles. From such an analysis on a commercially available polydisperse multicore particle system with an average particle size of 80 nm, we find that the MNP magnetic moment is proportional to the square root of the hydrodynamic size.
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| 67. |
- Frank, Christoph, et al.
(författare)
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Concordant and discordant familial cancer : Familial risks, proportions and population impact
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 140:7, s. 1510-1516
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Tidskriftsartikel (refereegranskat)abstract
- Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.
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| 68. |
- Frank, Christoph, et al.
(författare)
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Familial Associations Between Prostate Cancer and Other Cancers
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 71:2, s. 162-165
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PCa) has a large familial component, but understanding of its genetic basis is fragmentary. Breast cancers may be associated with PCa, but whether this is true for other tumor types is poorly established. We used a novel approach to study familial associations of any type of cancer with PCa. We assessed the relative risk (RR) for all types of tumors as a function of the number of first-degree relatives diagnosed with PCa. We hypothesized that for a familial association to be real, the RR for a given type of cancer should increase with the number of PCa diagnoses. In families with multiple PCa patients, significantly increased risks were observed for female breast cancer (RR 1.37 for families with three men with PCa), kidney cancer (RR 2.32), nervous system tumors (RR 1.77; RR 2.40 when PCa was diagnosed before age 70 yr), and myeloma (RR 2.44; RR 6.29 when PCa was diagnosed before age 70 yr). Some evidence of association was also found for melanoma (RR 1.82) and endocrine tumors (RR 2.18). The consistency and magnitude of the effects suggest that familial PCa is genetically associated with breast, kidney, and nervous system tumors and myeloma. This suggestion has implications for clinical counseling and design of genetic studies. Patient summary: It is known that prostate cancer runs in families, but it is not known whether other cancers are common in such families. We showed that at least breast, kidney, and nervous system tumors and myeloma occur more often than by chance. The present results demonstrate that prostate cancer (PCa) families show a statistical excess of some defined cancers. The cancers associated with PCa include breast, kidney, and nervous system tumors and myeloma and possibly melanoma and endocrine tumors.
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| 69. |
- Frank, Christoph, et al.
(författare)
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Risk of other Cancers in Families with Melanoma : Novel Familial Links
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A family history of cutaneous melanoma ('melanoma') is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.
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| 70. |
- Frank, Christoph, et al.
(författare)
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The population impact of familial cancer, a major cause of cancer
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 134:8, s. 906-1899
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Tidskriftsartikel (refereegranskat)abstract
- The population attributable fraction (PAF) defines the proportion of a disease that would be prevented if the exposure to a particular risk factor was avoided. Familial risk is a known risk factor for many cancers, but an unbiased estimation of the PAF for familial risk requires a large study population to include rare cancers. PAFs and their corresponding standardized incidence ratios (SIRs) were calculated for familial relative risk among first-degree relatives (FDRs) and second-degree relatives (SDRs) diagnosed with the same (concordant) invasive or in situ cancers. Calculations were based on the Swedish Family-Cancer Database considering 8,148,737 individuals. To assess environmental effects, PAFs were also calculated for concordant cancers among spouses. Almost all cancers showed a significant familial risk. The highest PAFs were found for the common cancers of the prostate (13.94%), breast (7.46%) and colorectum (6.78%) among the FDRs. In the FDRs, the overall PAF for any concordant cancer was 4.20%, but in the SDRs, it was only 0.34%. The overall PAFs for in situ cancers were 0.86% and 0.56% for the FDRs and SDRs, respectively. The overall independent familial PAF was 5.96% for the invasive and in situ cancers in the FDRs and SDRs. The cancers between spouses yielded an overall PAF of 0.14%. For esophageal cancer, the risk among spouses was higher than the familial risk. Our study shows that the overall familial PAF of 5.96%, although underestimated for sex-specific cancers, ranks as the third most common population burden after tobacco smoking and unhealthy diet.
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