277 research outputs found

    Simulating eddy current sensor outputs for blade tip timing

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    Blade tip timing is a contactless method used to monitor the vibration of blades in rotating machinery. Blade vibration and clearance are important diagnostic features for condition monitoring, including the detection of blade cracks. Eddy current sensors are a practical choice for blade tip timing and have been used extensively. As the data requirements from the timing measurement become more stringent and the systems become more complicated, including the use of multiple sensors, the ability to fully understand and optimize the measurement system becomes more important. This requires detailed modeling of eddy current sensors in the blade tip timing application; the current approaches often rely on experimental trials. Existing simulations for eddy current sensors have not considered the particular case of a blade rotating past the sensor. Hence, the novel aspect of this article is the development of a detailed quasi-static finite element model of the electro-magnetic field to simulate the integrated measured output of the sensor. This model is demonstrated by simulating the effect of tip clearance, blade geometry, and blade velocity on the output of the eddy current sensor. This allows an understanding of the sources of error in the blade time of arrival estimate and hence insight into the accuracy of the blade vibration measurement

    Decoupling of a Current-Biased Intrinsic Josephson Junction from its Environment

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    We have observed a dissipative phase diffusion branch in arrays of hysteretic high-Tc intrinsic Josephson junctions. By comparing the data with a thermal activation model we extract the impedance seen by the junction in which phase diffusion is occurring. At the plasma frequency this junction is isolated from its environment and it sees its own large (~ kilo Ohm) impedance. Our results suggest that stacks of Josephson junctions may be used for isolation purposes in the development of a solid state quantum computer

    Patient participation in undergraduate medical education: development of an informative patient resource

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    Patient participation in general practice-based undergraduate teaching: a focus group study of patient perspectives

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    Background: Patients make a crucial contribution to undergraduate medical education. While a national resource is available for patients participating in research, none is at yet available for education. / Aim: This study aimed to explore what information patients would like about participation in general practice-based undergraduate medical education and how they would like to obtain this information. / Design and Setting: We conducted two focus groups in London-based practices involved in both undergraduate and postgraduate teaching. / Method: Patients were recruited both with and without teaching experience using leaflets, posters and patient participation groups. An open-ended topic guide explored three areas: perceived barriers which participants anticipated, or had experienced; patient roles in medical education; and what help would support participation. Focus groups were audio-taped, transcribed and analysed thematically. / Results: Patients suggested ways of professionalising the teaching process, making information available to patients about confidentiality; iterative consent; and normalising teaching in the practice. Patients highlighted the importance of relationships: making information available about their GP’s involvement, and initiating student-patient interactions. Participants emphasised educational principles to maximise exchange of information including active participation of students; patient identification of student learner needs; and exchange of feedback. / Conclusion: This study will inform development of patient information resources to support their participation in teaching and access to information both before and during general practicebased teaching encounters

    Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

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    Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress. © 1999 Cancer Research Campaig

    Mutation Analysis of BRAF, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy

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    Among gynecologic cancers, ovarian cancer is the second most common and has the highest death rate. Cancer is a genetic disorder and arises due to the accumulation of somatic mutations in critical genes. An understanding of the genetic basis of ovarian cancer has implications both for early detection and for therapeutic intervention in this population of patients.Fifteen ovarian cancer cell lines, commonly used for in vitro experiments, were screened for mutations using bidirectional direct sequencing in all coding regions of BRAF, MEK1 and MEK2. BRAF mutations were identified in four of the fifteen ovarian cancer cell lines studied. Together, these four cell lines contained four different BRAF mutations, two of which were novel. ES-2 had the common B-Raf p.V600E mutation in exon 15 and Hey contained an exon 11 missense mutation, p.G464E. The two novel B-Raf mutants identified were a 5 amino acid heterozygous deletion p.N486-P490del in OV90, and an exon 4 missense substitution p.Q201H in OVCAR 10. One of the cell lines, ES-2, contained a mutation in MEK1, specifically, a novel heterozygous missense substitution, p.D67N which resulted from a nt 199 G-->A transition. None of the cell lines contained coding region mutations in MEK2. Functional characterization of the MEK1 mutant p.D67N by transient transfection with subsequent Western blot analysis demonstrated increased ERK phosphorylation as compared to controls.In this study, we report novel BRAF mutations in exon 4 and exon 12 and also report the first mutation in MEK1 associated with human cancer. Functional data indicate the MEK1 mutation may confer alteration of activation through the MAPK pathway. The significance of these findings is that BRAF and MEK1/2 mutations may be more common than anticipated in ovarian cancer which could have important implications for treatment of patients with this disease and suggests potential new therapeutic avenues

    The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

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    Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study
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