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| 2. |
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| 3. |
- Kang, E. Y., et al.
(författare)
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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
- 2023
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:5, s. 697-713
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
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| 5. |
- Sinn, T., et al.
(författare)
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Lessons learned from three university experiments onboard the REXUS/BEXUS sounding rockets and stratospheric balloons
- 2013
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Ingår i: 64th International Astronautical Congress 2013. - : International Astronautical Federation. - 9781629939094 ; , s. 7965-7976
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Konferensbidrag (refereegranskat)abstract
- Over the last three years the authors have been involved in three experiments that were or will be launched on sounding rockets and high altitude balloons with the REXUS/BEXUS program (Rocket-borne / Balloon-borne Experiments for University Students). The first experiment, called Suaineadh was launched from Esrange (Kiruna, Sweden) onboard REXUS 12 in March 2012. Suaineadh had the purpose of deploying a web in space by using centrifugal forces. The payload was lost during re-entry but was recovered 18 month later in early September 2013. StrathSat-R is the second experiment, which had the purpose of deploying two cube satellites with inflatable structures from the REXUS 13 sounding rocket, was launched first in May 2013 and will be launched a second time in spring 2014. The last experiment is the iSEDE experiment which has the goal of deploying an inflatable structure with disaggregated electronics from the high altitude balloon BEXUS15/16 in October 2013. All these experiments have been designed, built and flown in a timeframe of one and a half to two years. This paper will present the lessons learned in project management, outreach, experiment design, fabrication and manufacturing, software design and implementation, testing and validation as well as launch, flight and post-flight. Furthermore, the lessons learned during the recovery mission of Suaineadh will be discussed as well. All these experiments were designed, built and tested by a large group of university students of various disciplines and different nationalities. StrathSat-R and iSEDE were built completely at Strathclyde but the Suaineadh experiment was a joint project between Glasgow and Stockholm which was especially tricky during integration while approaching the experiment delivery deadline. This paper should help students and professionals across various disciplines to build and organise these kinds of projects more efficiently without making the same, sometimes expensive, mistakes all over again.
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| 6. |
- Barrett, C. F., et al.
(författare)
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Phylogenomics, biogeography and evolution in the American genus Brahea (Arecaceae)
- 2019
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Ingår i: Botanical Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4074 .- 1095-8339. ; 190:3, s. 242-259
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Tidskriftsartikel (refereegranskat)abstract
- Slow rates of molecular evolution at low taxonomic levels hamper studies of relationships among species and subsequent biogeographic and evolutionary analyses. An example is the genus Brahea, which is among the most poorly understood lineages of American palms and is characterized by a wide variety of growth forms and intermediate morphological features. We generated c. 400 kb of genome-scale data from all three genomes for the 11 currently described Brahea spp. to infer phylogenetic relationships, reconstruct ancestral growth form, estimate ancestral geographical ranges and test for niche differences among closely related species with geographical overlap. Relationships receive strong support and conform to previous subgeneric assignments, except for placement of the dwarf species B. moorei in Brahea subgenus Erythea. Our robust phylogenetic hypothesis reveals trends in growth form, including an overall increase in height in the B. armata clade and independent evolution of dwarf forms from taller ancestors in the B. pimo and B. dulcis clades. Ancestral range estimation reveals roles of dispersal (e.g. B. edulis on Guadalupe Island) and putative divergence within geographical regions in some cases (e.g. in the B. armata clade) but is equivocal in others (e.g. in the B. pimo clade). We find evidence of niche non-equivalency among species in the B. armata clade in north-western Mexico and some evidence of niche non-equivalency between B. berlandieri and B. dulcis, the former of which is synonymized under B. dulcis. Our findings have implications for the complex biogeographic history in Central America and Mexico, suggesting that divergence within regions and dispersal are the predominant processes of species diversification. Future studies should include population-level sampling across the genus, along with morphological and ecological information, to assess distinctness among species and, particularly, levels of gene flow, in an integrative fashion.
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| 7. |
- Boecker, W., et al.
(författare)
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Differentiation and histogenesis of syringomatous tumour of the nipple and low-grade adenosquamous carcinoma: evidence for a common origin
- 2014
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 65:1, s. 9-23
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Syringomatous tumour of the nipple and low-grade adenosquamous carcinoma (LGAdSC) of the breast are regarded as distinct entities. To clarify the nature of these two lesions, we compared the expression of different lineage/differentiation markers in 12 syringomatous tumours of the nipple, nine LGAdSCs, and normal breast epithelium. Methods and results: Using triple immunofluorescence labelling and quantitative RT-PCR for keratins, p63, and smooth muscle actin, we demonstrated that syringomatous tumour and LGAdSC contain p63+/K5/14+ tumour cells, K10+ squamous cells, and K8/18+ glandular cells, with intermediary cells being found in both lineages. Identical p63+/K5/14+ cells were also found in the normal breast duct epithelium. Conclusions: Our data provide evidence that syringomatous tumour of the nipple and LGAdSC are identical or nearly identical lesions. They contain p63+/K5/14+ cells as the key cells from which the K10+ squamous lineage and the K8/18+ glandular lineage arise. On the basis of our findings in normal breast tissue and associated benign lesions, we suggest that p63+/K5/14+ cells of the normal breast duct epithelium or early related cells might play a key role in the neoplastic transformation of both syringomatous tumour and LGAdSC. We propose that the differentiation patterns found in both lesions reflect the early ontogenetic stages of the normal breast epithelium.
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| 8. |
- Heinze, Karolin, et al.
(författare)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Tidskriftsartikel (refereegranskat)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 9. |
- Kang, E. Y., et al.
(författare)
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MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma
- 2022
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480, s. 855-871
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Tidskriftsartikel (refereegranskat)abstract
- Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
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| 10. |
- Meagher, N. S., et al.
(författare)
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A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases
- 2019
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 32, s. 1834-1846
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Tidskriftsartikel (refereegranskat)abstract
- Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7−/CK20+/CDX2+/PAX8−. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1–50% of tumor cells) and diffuse (>50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker indistinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice. © 2019, The Author(s), under exclusive licensc to United States & Canadian Academy of Pathology.
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| 11. |
- Barrett, C. F., et al.
(författare)
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Ancient Polyploidy and Genome Evolution in Palms
- 2019
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 11:5, s. 1501-1511
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of genome evolution are fundamental to our understanding of adaptation and the generation and maintenance of biodiversity, yet genome dynamics are still poorly characterized in many clades. Strong correlations between variation in genomic attributes and species diversity across the plant tree of life suggest that polyploidy or other mechanisms of genome size change confer selective advantages due to the introduction of genomic novelty. Palms (order Arecales, family Arecaceae) are diverse, widespread, and dominant in tropical ecosystems, yet little is known about genome evolution in this ecologically and economically important clade. Here, we take a phylogenetic comparative approach to investigate palm genome dynamics using genomic and transcriptomic data in combination with a recent, densely sampled, phylogenetic tree. We find conclusive evidence of a paleopolyploid event shared by the ancestor of palms but not with the sister clade, Dasypogonales. We find evidence of incremental chromosome number change in the palms as opposed to one of recurrent polyploidy. We find strong phylogenetic signal in chromosome number, but no signal in genome size, and further no correlation between the two when correcting for phylogenetic relationships. Palms thus add to a growing number of diverse, ecologically successful clades with evidence of whole-genome duplication, sister to a species-poor clade with no evidence of such an event. Disentangling the causes of genome size variation in palms moves us closer to understanding the genomic conditions facilitating adaptive radiation and ecological dominance in an evolutionarily successful, emblematic tropical clade.
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| 15. |
- Mao, Huina, et al.
(författare)
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Simulation and control of a space web deployed by centrifugal forces in a sounding rocket experiment
- 2016
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Ingår i: AIAA Modeling and Simulation Technologies Conference, 2016. - Reston, Virginia : American Institute of Aeronautics and Astronautics Inc, AIAA. - 9781624104299
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Konferensbidrag (refereegranskat)abstract
- A deployable space web is a flexible structure that can act as a lightweight platform for construction of large structures in space. In order to save space and energy for small deployable structures, a one-step deployment method was a possible choice for future web deployment without complicated extending mechanisms. The aim of the Suaineadh experiment was to deploy and stabilize a space web by centrifugal forces and act as a test bed of the one-step deployment. Suaineadh, a 2 × 2 m2 space web, was ejected from the nose cone of REXUS-12 sounding rocket and deployed in a micro-gravity environment. A developed control law and a reaction wheel were used to control the deployment. Results from ground tests, simulations and former sounding rocket experiments were used to design the structure, folding pattern, control parameters and the deployment. During the experiment, the web was deployed but entanglements occurred since the web did not start to deploy at the specified proper initial angular velocity. It might be due to the broken inertial measurement unit which failed to detect the required spin rate of the hub or other unknown problems. The deployment dynamics was reconstructed from the information recorded by inertial measurement units and cameras. Simulations show that if the Suaineadh space web started to deploy at the specified proper angular velocity, the web would most likely have been deployed and stabilized in space by the motor, reaction wheel and controller used in the experiment. In actual flight, out-of-plane motions were observed both in deployment and stabilization phases. In order to stabilize the out-of-plane motions and reduce the risk of entanglement observed from experiment, simulation results show that small reaction wheels could be used before or during web deployment. Tape springs could also be used as web arms to avoid entanglement.
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| 17. |
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| 18. |
- Sinn, T., et al.
(författare)
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Design and development of deployable Self-inflating Adaptive Membrane
- 2012
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Ingår i: 53rd Structures, Structural Dynamics, and Materials Conference (SDM) 2012. - Reston, Virigina : American Institute of Aeronautics and Astronautics. ; , s. AIAA 2012-1517-
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Konferensbidrag (refereegranskat)abstract
- Space structures nowadays are often designed to serve just one objective during their mission life, examples include truss structures that are used as support structures, solar sails for propulsion or antennas for communication. Each and every single one of these structures is optimized to serve just their distinct purpose and are more or less useless for the rest of the mission and therefore dead weight. By developing a smart structure that can change its shape and therefore adapt to different mission requirements in a single structure, the flexibility of the spacecraft can be increased by greatly decreasing the mass of the entire system. This paper will introduce such an adaptive structure called the Self-inflating Adaptive Membrane (SAM) concept which is being developed at the Advanced Space Concepts Laboratory of the University of Strathclyde. An idea presented in this paper is to adapt these basic changeable elements from nature's heliotropism. Heliotropism describes a movement of a plant towards the sun during a day; the movement is initiated by turgor pressure change between adjacent cells. The shape change of the global structure can be significant by adding up these local changes induced by local elements, for example the cell's length. To imitate the turgor pressure change between the motor cells in plants to space structures, piezoelectric micro pumps are added between two neighboring cells. A passive inflation technique is used for deploying the membrane at its destination in space. The trapped air in the spheres will inflate the spheres when subjected to vacuum, therefore no pump or secondary active deployment methods are needed. The paper will present the idea behind the adaption of nature's heliotropism principle to space structures. The feasibility of the residual air inflation method is verified by LS-DYNA simulations and prototype bench tests under vacuum conditions. Additionally, manufacturing techniques and folding patterns are presented to optimize the actual bench test structure and to minimize the required storage volume. It is shown that through a bio-inspired concept, a high ratio of adaptability of the membrane can be obtained. The paper concludes with the design of a technology demonstrator for a sounding rocket experiment to be launched in March 2013 from the Swedish launch side Esrange.
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| 19. |
- Sinn, T., et al.
(författare)
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Results of rexus12's suaineadh experiment : Deployment of a spinning space web in micro gravity conditions
- 2012
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Ingår i: Proceedings of the International Astronautical Congress, IAC. - : International Astronautical Federation. - 9781622769797 ; , s. 803-810
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Konferensbidrag (refereegranskat)abstract
- On the 19th of March 2012, the Suaineadh experiment was launched onboard the sounding rocket REXUS12 (Rocket Experiments for University Students) from the Swedish launch base ESRANGE in Kiruna. The Suaineadh experiment served as a technology demonstrator for a space web deployed by a spinning assembly. The deployment of this web is a stepping stone for the development of ever larger structures in space. Such a structure could serve as a substructure for solar arrays, transmitters and/or antennas. The team was comprised of students from the University of Strathclyde (Glasgow, UK), the University of Glasgow (Glasgow, UK) and the Royal Institute of Technology (Stockholm, Sweden), designing, manufacturing and testing the experiment over the past 24 months. Following launch, the experiment was ejected from the ejection barrel located within the nosecone of the rocket. Centrifugal forces acting upon the space webs spinning assembly were used to stabilise the experiment's platform. A specifically designed spinning reaction wheel, with an active control method, was used. Once the experiment's motion was controlled, a 2 m by 2 m space web is released. Four daughter sections situated in the corners of the square web served as masses to stabilise the web due to the centrifugal forces acting on them. The four daughter sections contained inertial measurement units (IMUs). Each IMU provided acceleration and velocity measurements in all three directions. Through this, the positions of the four corners could be found through integration with respect to known time of the accelerations and rotations. Furthermore, four cameras mounted on the central hub section captured high resolution imagery of the deployment process. After the launch of REXUS12, the recovery helicopter was unable to locate the ejected experiment, but 22 pictures were received over the wireless connection between the experiment and the rocket. The last received picture was taken at the commencement of web deployment. Inspection of these pictures allowed the assumption that the experiment was fully functional after ejection, but perhaps through tumbling of either the experiment or the rocket, the wireless connection was interrupted. A recovery mission in the middle of August was only able to find the REXUS12 motor and the payload impact location.
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