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| 2. |
- Abdesselam, A., et al.
(författare)
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Engineering for the ATLAS SemiConductor Tracker (SCT) end-cap
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS SemiConductor Tracker (SCT) is a silicon-strip tracking detector which forms part of the ATLAS inner detector. The SCT is designed to track charged particles produced in proton-proton collisions at the Large Hadron Collider (LHC) at CERN at an energy of 14 TeV. The tracker is made up of a central barrel and two identical end-caps. The barrel contains 2112 silicon modules, while each end-cap contains 988 modules. The overall tracking performance depends not only on the intrinsic measurement precision of the modules but also on the characteristics of the whole assembly, in particular, the stability and the total material budget. This paper describes the engineering design and construction of the SCT end-caps, which are required to support mechanically the silicon modules, supply services to them and provide a suitable environment within the inner detector. Critical engineering choices are highlighted and innovative solutions are presented - these will be of interest to other builders of large-scale tracking detectors. The SCT end-caps will be fully connected at the start of 2008. Further commissioning will continue, to be ready for proton-proton collision data in 2008.
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| 3. |
- Bates, R. L., et al.
(författare)
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The ATLAS SCT grounding and shielding concept and implementation
- 2012
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 7, s. P03005-
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the design and implementation of the grounding and shielding system for the ATLAS SemiConductor Tracker (SCT). The mitigation of electromagnetic interference and noise pickup through power lines is the critical design goal as they have the potential to jeopardize the electrical performance. We accomplish this by adhering to the ATLAS grounding rules, by avoiding ground loops and isolating the different subdetectors. Noise sources are identified and design rules to protect the SCT against them are described. A rigorous implementation of the design was crucial to achieve the required performance. This paper highlights the location, connection and assembly of the different components that affect the grounding and shielding system: cables, filters, cooling pipes, shielding enclosure, power supplies and others. Special care is taken with the electrical properties of materials and joints. The monitoring of the grounding system during the installation period is also discussed. Finally, after connecting more than four thousand SCT modules to all of their services, electrical, mechanical and thermal within the wider ATLAS experimental environment, dedicated tests show that noise pickup is minimised.
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| 4. |
- Li, Bo, et al.
(författare)
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Therapeutic rationale to target highly expressed CDK7 conferring poor outcomes in triple-negative breast cancer
- 2017
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Ingår i: Cancer Research. - 0008-5472. ; 77:14, s. 3834-3845
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative breast cancer (TNBC) patients commonly exhibit poor prognosis and high relapse after treatment, but there remains a lack of biomarkers and effective targeted therapies for this disease. Here, we report evidence highlighting the cell-cycle–related kinase CDK7 as a driver and candidate therapeutic target in TNBC. Using publicly available transcriptomic data from a collated set of TNBC patients (n ¼ 383) and the METABRIC TNBC dataset (n ¼ 217), we found CDK7 mRNA levels to be correlated with patient prognosis. High CDK7 protein expression was associated with poor prognosis within the RATHER TNBC cohort (n ¼ 109) and the METABRIC TNBC cohort (n ¼ 203). The highly specific CDK7 kinase inhibitors, BS-181 and THZ1, each downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition, with THZ1 exhibiting 500-fold greater potency than BS-181. Mechanistic investigations revealed that the survival of MDA-MB-231 TNBC cells relied heavily on the BCL-2/BCL-XL signaling axes in cells. Accordingly, we found that combining the BCL-2/BCL-XL inhibitors ABT-263/ABT199 with the CDK7 inhibitor THZ1 synergized in producing growth inhibition and apoptosis of human TNBC cells. Collectively, our results highlight elevated CDK7 expression as a candidate biomarker of poor prognosis in TNBC, and they offer a preclinical proof of concept for combining CDK7 and BCL-2/BCL-XL inhibitors as a mechanism-based therapeutic strategy to improve TNBC treatment.
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| 5. |
- Walsh, Louise, et al.
(författare)
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BET Inhibition as a Rational Therapeutic Strategy for Invasive Lobular Breast Cancer
- 2019
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 25:23, s. 7139-7150
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Invasive lobular carcinoma (ILC) is a subtype of breast cancer accounting for 10% of breast tumors. The majority of patients are treated with endocrine therapy; however, endocrine resistance is common in estrogen receptor-positive breast cancer and new therapeutic strategies are needed. Bromodomain and extraterminal inhibitors (BETi) are effective in diverse types of breast cancer but they have not yet been assessed in ILC.EXPERIMENTAL DESIGN: We assessed whether targeting the BET proteins with JQ1 could serve as an effective therapeutic strategy in ILC in both 2D and 3D models. We used dynamic BH3 profiling and RNA-sequencing (RNA-seq) to identify transcriptional reprograming enabling resistance to JQ1-induced apoptosis. As part of the RATHER study, we obtained copy-number alterations and RNA-seq on 61 ILC patient samples.RESULTS: Certain ILC cell lines were sensitive to JQ1, while others were intrinsically resistant to JQ1-induced apoptosis. JQ1 treatment led to an enhanced dependence on antiapoptotic proteins and a transcriptional rewiring inducing fibroblast growth factor receptor 1 (FGFR1). This increase in FGFR1 was also evident in invasive ductal carcinoma (IDC) cell lines. The combination of JQ1 and FGFR1 inhibitors was highly effective at inhibiting growth in both 2D and 3D models of ILC and IDC. Interestingly, we found in the RATHER cohort of 61 ILC patients that 20% had FGFR1 amplification and we showed that high BRD3 mRNA expression was associated with poor survival specifically in ILC.CONCLUSIONS: We provide evidence that BETi either alone or in combination with FGFR1 inhibitors or BH3 mimetics may be a useful therapeutic strategy for recurrent ILC patients.
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| 7. |
- Khan, Sammyh, 1979-, et al.
(författare)
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Can Raising Awareness about the Psychological Causes of Obesity Reduce Obesity Stigma?
- 2018
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Ingår i: Health Communication. - : Routledge. - 1041-0236 .- 1532-7027. ; 33:5, s. 585-592
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Tidskriftsartikel (refereegranskat)abstract
- Obesity stigma largely remains a socially acceptable bias with harmful outcomes for its victims. While many accounts have been put forward to explain the bias, the role of obesity etiology beliefs has received little scrutiny. The research examined the effect that beliefs about the psychological etiology of obesity have on the expression of obesity stigma and the mechanisms underpinning this effect. Participants (N=463) were asked to evaluate a target person with obesity after reading one of three possible etiologies: psychological, genetic, or behavioral. The presentation of a psychological etiology of obesity elicited less prejudice compared to behavioral causes but greater prejudice compared to genetic causes; observed differences were found to be a function of the agency ascribed to the target's obesity and empathy expressed for the target. The findings highlight the impact that communicating obesity in terms of psychological causes can have for the expression of obesity stigma.
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| 8. |
- Michaut, Magali, et al.
(författare)
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Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.
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| 9. |
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| 10. |
- Tarrant, M., et al.
(författare)
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Patient experiences of a bariatric group programme for managing obesity : A qualitative interview study
- 2017
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Ingår i: British Journal of Health Psychology. - : John Wiley & Sons. - 1359-107X .- 2044-8287. ; 22:1, s. 77-93
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: People with obesity experience a range of physical and psychological ill-health outcomes. This study examined patients' experiences of a group-based programme for the management of morbid obesity delivered within the UK National Health Service. The focus of the study was on the emerging dynamic of the group and patients' perceptions of its impact on health outcomes.Design: A qualitative interview study was conducted and involved patients recruited from a Tier 3 bariatric service in South West England. Verbatim transcripts were analysed using thematic analysis.Methods: Twenty patients (12 females) with a BMI >= 35 kg/m(2) participated in a semi-structured one-to-one interview. Participants had been registered with the bariatric service for at least 6 months. None of the participants had had bariatric surgery.Results: Most participants felt that they had benefited from participating in the group programme and talked about the group as a resource for lifestyle change. Participants' narratives centred on the emergence of a sense of self based upon their participation in the group: establishing psychological connections to other patients, or shared social identity, was regarded as a key mechanism through which the programme's educational material was accessed, and underpinned the experience of social support within the group. Through interaction with other patients, involving the sharing of personal experiences and challenges, participants came to experience their weight ` problem' through a collective lens that they felt empowered them to initiate and sustain individual lifestyle change.Discussion: Bariatric care groups have the potential to support lifestyle change and weight loss and may help address the psychological needs of patients. Nurturing a sense of shared social identity amongst patients with morbid obesity should be a core aim of the care pathway and may provide the foundation for successful translation of dietetic content in group programmes.
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