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Sökning: WFRF:(Murphy Patrick)

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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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3.
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4.
  • Abbasi, Rasha, et al. (författare)
  • IceCube search for neutrinos from GRB 221009A
  • 2023
  • Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
  • Konferensbidrag (refereegranskat)abstract
    •  GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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5.
  • Coyle, Krysta M., et al. (författare)
  • Breast cancer subtype dictates DNA methylation and ALDH1A3-mediated expression of tumor suppressor RARRES1
  • 2016
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:28, s. 44096-44112
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determine patient prognosis and potential options for targeted therapy. Among breast cancer subtypes, tumors of basal-like and claudin-low subtypes are typically associated with worse patient outcomes, are primarily classified as triple-negative breast cancers (TNBC), and cannot be treated with existing hormone-receptor-targeted therapies. Understanding the molecular basis of these subtypes will lead to the development of more effective treatment options for TNBC. In this study, we focus on retinoic acid receptor responder 1 (RARRES1) as a paradigm to determine if breast cancer subtype dictates protein function and gene expression regulation. Patient tumor dataset analysis and gene expression studies of a 26 cell-line panel, representing the five breast cancer subtypes, demonstrate that RARRES1 expression is greatest in basal-like TNBCs. Cell proliferation and tumor growth assays reveal that RARRES1 is a tumor suppressor in TNBC. Furthermore, gene expression studies, Illumina HumanMethylation450 arrays, and chromatin immunoprecipitation demonstrate that expression of RARRES1 is retained in basal-like breast cancers due to hypomethylation of the promoter. Additionally, expression of the cancer stem cell marker, aldehyde dehydrogenase 1A3, which provides the required ligand (retinoic acid) for RARRES1 transcription, is also specific to the basal-like subtype. We functionally demonstrate that the combination of promoter methylation and retinoic acid signaling dictates expression of tumor suppressor RARRES1 in a subtype-specific manner. These findings provide a precedent for a therapeutically-inducible tumor suppressor and suggest novel avenues of therapeutic intervention for patients with basal-like breast cancer.
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6.
  • de Fréin, Ruairí, et al. (författare)
  • Integration of QoS Metrics, Rules and Semantic Uplift for Advanced IPTV Monitoring
  • 2014
  • Ingår i: Journal of Network and Systems Management. - : Springer. - 1573-7705 .- 1064-7570. ; 23:3, s. 1-36
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing and variable traffic demands due to triple play services pose significant Internet Protocol Television (IPTV) resource management challenges for service providers. Managing subscriber expectations via consolidated IPTV quality reporting will play a crucial role in guaranteeing return-on-investment for players in the increasingly competitive IPTV delivery ecosystem. We propose a fault diagnosis and problem isolation solution that addresses the IPTV monitoring challenge and recommends problem-specific remedial action. IPTV delivery-specific metrics are collected at various points in the delivery topology, the residential gateway and the Digital Subscriber Line Access Multiplexer through to the video Head-End. They are then pre-processed using new metric rules. A semantic uplift engine takes these raw metric logs; it then transforms them into World Wide Web Consortium’s standard Resource Description Framework for knowledge representation and annotates them with expert knowledge from the IPTV domain. This system is then integrated with a monitoring visualization framework that displays monitoring events, alarms, and recommends solutions. A suite of IPTV fault scenarios is presented and used to evaluate the feasibility of the solution. We demonstrate that professional service providers can provide timely reports on the quality of IPTV service delivery using this system.
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7.
  • DEath, Maureen, et al. (författare)
  • Participants Experiences of a Sexual Counseling Intervention During Cardiac Rehabilitation A Nested Qualitative Study Within the CHARMS Pilot Randomized Controlled Trial
  • 2018
  • Ingår i: Journal of Cardiovascular Nursing. - : LIPPINCOTT WILLIAMS & WILKINS. - 0889-4655 .- 1550-5049. ; 33:5, s. E35-E45
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: International guidelines recommend sexual assessment and counseling be offered to all patients with cardiovascular disease during cardiac rehabilitation. However, sexual problems are infrequently addressed. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention is a complex, multilevel intervention designed to increase the provision of sexual counseling in cardiac rehabilitation. It was piloted in 2 cardiac rehabilitation centers to assess the acceptability and feasibility of the intervention and to inform and refine a definitive cluster randomized controlled trial protocol. Objectives: The aim of this study was to explore the experiences, perceptions, and opinions of patients, partners, and cardiac rehabilitation staff who participated in the CHARMS staff-led patient education class. Methods: A qualitative, descriptive study using semistructured interviews to collect the data. Cardiac rehabilitation staff (n = 8) were interviewed when the intervention commenced in their center and 3 months later (n = 6). Patients (n = 19) and partners (n = 2) were interviewed after delivery of the class; 7 were interviewed again 3 months postintervention to explore temporal changes in opinions. Results: Most cardiac rehabilitation staff were comfortable delivering the CHARMS intervention but would prefer a less structured format. Some staff perceived discomfort among patients. Few patients reported discomfort. Most patients and partners considered that the intervention was a welcome and acceptable part of a cardiac rehabilitation program. Conclusion: Incorporating sexual counseling into cardiac rehabilitation programs is feasible. Although the views of the patients and staff diverged on a number of issues including the perceived comfort of patients, its inclusion was welcomed by patients and was acceptable overall to both staff and patients.
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8.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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9.
  • Murphy, Patrick J., et al. (författare)
  • Sexual counselling for patients with cardiovascular disease: protocol for a pilot study of the CHARMS sexual counselling intervention
  • 2016
  • Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 6:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Sexual problems are common with cardiovascular disease, and can negatively impact quality of life. To address sexual problems, guidelines have identified the importance of sexual counselling during cardiac rehabilitation, yet this is rarely provided. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention aims to improve the provision of sexual counselling in cardiac rehabilitation in Ireland. Methods and analysis This is a multicentre pilot study for the CHARMS intervention, a complex, multilevel intervention delivered within hospital-based cardiac rehabilitation programmes. The intervention includes (1) training in sexual counselling for staff, (2) a staff-led patient education and support intervention embedded within the cardiac rehabilitation programme, (3) a patient information booklet and (4) an awareness raising poster. The intervention will be delivered in two randomly selected cardiac rehabilitation centres. In each centre 30 patients will be recruited, and partners will also be invited to participate. Data will be collected from staff and patients/partners at T1 (study entry), T2 (3-month follow-up) and T3 (6-month follow-up). The primary outcome for patients/partners will be scores on the Sexual Self-Perception and Adjustment Questionnaire. Secondary outcomes for patients/partners will include relationship satisfaction; satisfaction with and barriers to sexual counselling in services; sexual activity, functioning and knowledge; physical and psychological well-being. Secondary outcomes for staff will include sexuality-related practice; barriers to sexual counselling; self-ratings of capability, opportunity and motivation; sexual attitudes and beliefs; knowledge of cardiovascular disease and sex. Fidelity of intervention delivery will be assessed using trainer self-reports, researcher-coded audio recordings and exit interviews. Longitudinal feasibility data will be gathered from patients/partners and staff via questionnaires and interviews. Ethics and dissemination This study is approved by the Research Ethics Committee (REC) of the National University of Ireland, Galway. Findings will be disseminated to cardiac rehabilitation staff, patients/partners and relevant policymakers via appropriate publications and presentations.
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10.
  • Murphy, Patrick J., et al. (författare)
  • The CHARMS pilot study: a multi-method assessment of the feasibility of a sexual counselling implementation intervention in cardiac rehabilitation in Ireland
  • 2018
  • Ingår i: Pilot and Feasibility Studies. - : BioMed Central. - 2055-5784. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Many people living with cardiovascular disease (CVD) are affected by sexual problems associated with the condition. International guidelines recommend all patients with CVD should receive sexual counselling, yet this is rarely provided by health professionals. The current study piloted the Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention, a complex multi-level intervention designed to increase the implementation of sexual counselling guidelines in hospital-based cardiac rehabilitation (CR) in Ireland.
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