58 research outputs found
Herstory Cafe: Helena Gutteridge, Vancouver\u27s First \u27Alderman\u27.
No full textIllustrated talk by Irene Howard, author of "The Struggle for Social Justice in British Columbia: Helena Gutteridge, the Unknown Reformer\u27
Jon Richardson & The Futurenauts Live Show: The Future of Human Animal Communication
No full textIn this first ever full line-up LIVE show to kick off Series 5 Jon, Mark & Ed are joined by special guests Tom Mustil (author of ‘How to speak whale’) and Holly Root Gutteridge (researcher in bioacoustics) in an incredible philosophical and scatological adventure into the past, present and future of human: animal communication. Featuring our best animal impersonations, ‘Guess the animal’ sound clips and why what Sea Otters get up to is NSFW.</p
An investigation into the effects of the epidermal growth factor receptor tyrosine kinase inhibitor "Gefitinib" on human breast cancer
No full textBackground. In vitro studies have shown that ER+ acquired tamoxifen resistant MCF7 breast cancer cell lines can show elevated levels of EGFR expression with an increase in its subsequent signalling pathway(s) and that these are growth inhibited by gefitinib, an EGFR tyrosine kinase inhibitor. This thesis examines the effect of gefitinib on tamoxifen resistant human breast cancer in the clinical setting and in an ‘in-vivo’ mouse model.
Patients and Methods. This phase 2 clinical study recruited 54 patients. 28 were oestrogen receptor positive and had progressed on tamoxifen treatment(acquired resistance), the other 26 (48.1%) were oestrogen receptor negative(de novo resistance). Patients were given a loading dose of 1000mg gefitinib on Day 1 and then gefitinib 500mg as a once daily oral dosing until evidence of disease progression. Clinical data were recorded. Sequential tumour biopsies were taken pre-treatment, after 8 weeks therapy and at the development of resistance and analysed immunocytochemically to identify predictive factors for response to treatment and also to see the effect of treatment and resistance on tumour biology, encompassing monitoring steroid receptors, EGFR, HER2 and IGFR, downstream kinases MAPK and AKT, and the proliferation marker Ki67. In parallel with the clinical study, ER+ acquired tamoxifen resistant MCF7 xenografts (TAMR) were grown in nude mice in the presence of tamoxifen and treated with gefitinib 50mg per day orally (designated 3 treatment) or tamoxifen alone (designated control) and monitored for impact on tumour growth.
Results. In the phase 2 study gefitinib treatment was well tolerated with an overall clinical benefit rate of 33.3% (n=18/54). Pre-treatment oestrogen receptor positivity was associated with tumour response to gefitinib (p=0.015, longer TTP (p = 0.015), and with clinical benefit (CB) in 53.6 % of the ER+ acquired tamoxifen resistant patients. In contrast, the clinical benefit rate was minimal in the steroid receptor negative patient cohort (11.5%). All patients in this series expressed detectable levels of EGFR, but high pre-treatment levels of EGFR predicted a poorer outcome (p=0.075) Only patients achieving CB had a significant fall in Ki67 staining as measured at 8 weeks versus pretreatment levels (p=0.024), and that Ki67 levels were lower in CB than PD patients at this time. We observed lower levels of EGFR phosphorylation at this time point in some CB patients. Further examination of the CB pts who showed a >10% decline in EGFR phosphorylation revealed decreases in phosphorylation of MAPK and also in Ki67.
TAMR xenografts expressed high levels of EGFR as previously observed in vitro. Their growth was significantly inhibited by gefitinib (p=0.039) over the study period while after only 2 weeks of gefitinib treatment tumours showed a decrease in the level of Ki67 staining (p = 0.068).
Conclusion. Acquired tamoxifen resistance in vivo both in patients and in a xenograft model appears to be in part mediated through EGFR pathway signalling and this can be blocked and growth inhibited with gefitinib. In ER 4 negative tumours the effects of gefitinib were less striking, suggesting alternative signalling pathways are dominant in promoting their growth despite obvious overexpression of EGFR
An investigation into the effects of the epidermal growth factor receptor tyrosine kinase inhibitor "Gefitinib" on human breast cancer
No full textBackground. In vitro studies have shown that ER+ acquired tamoxifen resistant MCF7 breast cancer cell lines can show elevated levels of EGFR expression with an increase in its subsequent signalling pathway(s) and that these are growth inhibited by gefitinib, an EGFR tyrosine kinase inhibitor. This thesis examines the effect of gefitinib on tamoxifen resistant human breast cancer in the clinical setting and in an ‘in-vivo’ mouse model.
Patients and Methods. This phase 2 clinical study recruited 54 patients. 28 were oestrogen receptor positive and had progressed on tamoxifen treatment(acquired resistance), the other 26 (48.1%) were oestrogen receptor negative(de novo resistance). Patients were given a loading dose of 1000mg gefitinib on Day 1 and then gefitinib 500mg as a once daily oral dosing until evidence of disease progression. Clinical data were recorded. Sequential tumour biopsies were taken pre-treatment, after 8 weeks therapy and at the development of resistance and analysed immunocytochemically to identify predictive factors for response to treatment and also to see the effect of treatment and resistance on tumour biology, encompassing monitoring steroid receptors, EGFR, HER2 and IGFR, downstream kinases MAPK and AKT, and the proliferation marker Ki67. In parallel with the clinical study, ER+ acquired tamoxifen resistant MCF7 xenografts (TAMR) were grown in nude mice in the presence of tamoxifen and treated with gefitinib 50mg per day orally (designated 3 treatment) or tamoxifen alone (designated control) and monitored for impact on tumour growth.
Results. In the phase 2 study gefitinib treatment was well tolerated with an overall clinical benefit rate of 33.3% (n=18/54). Pre-treatment oestrogen receptor positivity was associated with tumour response to gefitinib (p=0.015, longer TTP (p = 0.015), and with clinical benefit (CB) in 53.6 % of the ER+ acquired tamoxifen resistant patients. In contrast, the clinical benefit rate was minimal in the steroid receptor negative patient cohort (11.5%). All patients in this series expressed detectable levels of EGFR, but high pre-treatment levels of EGFR predicted a poorer outcome (p=0.075) Only patients achieving CB had a significant fall in Ki67 staining as measured at 8 weeks versus pretreatment levels (p=0.024), and that Ki67 levels were lower in CB than PD patients at this time. We observed lower levels of EGFR phosphorylation at this time point in some CB patients. Further examination of the CB pts who showed a >10% decline in EGFR phosphorylation revealed decreases in phosphorylation of MAPK and also in Ki67.
TAMR xenografts expressed high levels of EGFR as previously observed in vitro. Their growth was significantly inhibited by gefitinib (p=0.039) over the study period while after only 2 weeks of gefitinib treatment tumours showed a decrease in the level of Ki67 staining (p = 0.068).
Conclusion. Acquired tamoxifen resistance in vivo both in patients and in a xenograft model appears to be in part mediated through EGFR pathway signalling and this can be blocked and growth inhibited with gefitinib. In ER 4 negative tumours the effects of gefitinib were less striking, suggesting alternative signalling pathways are dominant in promoting their growth despite obvious overexpression of EGFR
Crystal Structure EPrints: Publication @ Source Through the Open Archive Initiative
No full textRecent advances in crystallographic instrumentation and computational resources have caused an explosion of crystallographic data, as shown by the recent exponential growth of the CSD [1]. However, even this is considered to be lower than expected, following the introduction of area detection. The reason for this is clearly identified as a publication bottleneck, which will become even more severe with developments in high throughput crystallography [2]. As a result of this situation, the user community is deprived of valuable information, and the funding bodies are getting a poor return for their investments!
Electronic publishing has helped to make some inroads into the problem, and is already an integral part of chemical and crystallographic publishing. This has dramatically reduced the turnaround time in the publication process, but the system still fails to keep apace of the generation of structural information, mainly because of the continued reliance on traditional protocols for the assembly of manuscripts and their peer review. The need to maintain some kind of review process is clear, and this makes the sometimes-used direct submission of structures to the CCDC “unpopular”.
Unlike the mathematical and electronic sciences, the chemical sciences have been reluctant to embrace the 'preprint concept' [3]: the one exception has been the efforts of rapid electronic communications journals. This poster outlines a pre-print procedure for the rapid and effective dissemination of structural information to the scientific community which removes the lengthy peer review process that hampers traditional publication routes, but provides an alternative mechanism. Crystallographic EPrints are built on a concept developed in the Computer Science community [4] whereby an author may reveal to the public archives of information. An Eprint makes available all raw, derived and results data from a crystallographic experiment via a searchable and hierarchical system. At the top searchable level this metadata includes bibliographic and chemical identifier items which allow access to a secondary level of searchable crystallographic items which are directly linked to the associated archived data.
Hence the results of a crystal structure determination may be disseminated in a manner that anyone wishing to utilise the information may access the entire archive of data related to it and assess its validity and worth
eCrystallographyDataReports: an open archive route for the reporting and dissemination of crystal structures
No full textAdvances in crystallographic instrumentation and computational resources have caused an explosion of crystallographic data, as shown by the recent exponential growth of the Cambridge Structural Database (CSD) [1]. However, even this is considered to be lower than expected, following the introduction of area detection. The reason for this is clearly identified as a publication bottleneck [2], which can only become even more severe with developments in high throughput crystallography [3]. As a result of this situation, the user community is deprived of valuable information, and the funding bodies are getting a poor return for their investments!
Unlike the mathematical and electronic sciences, the chemical sciences have been reluctant to embrace the 'preprint concept' [4]: the one exception has been the efforts of rapid electronic communications journals. This poster outlines a publication at source procedure for the rapid and effective dissemination of structural information to the scientific community which removes the lengthy peer review process that hampers traditional publication routes, but provides an alternative mechanism. eCrystallographyDataReports are built on a concept developed in the Computer Science community, the Open Archive Initiative (OAI) [5], whereby an author may reveal to the public archives of information. OAI software, known as ePrints [6], has been modified to implement this new type of open archive. An eCrystallographyDataReport makes available all raw, derived and results data from a crystallographic experiment via a searchable and hierarchical system. At the top searchable level this metadata includes bibliographic and chemical identifier items which allow access to a secondary level of crystallographic items which are directly linked to the associated archived data.
The 'core bibliographic data' is made available to the public domain by the Open Archive Initiative Protocol for Metadata Harvesting (OAI-PMH) [7] so that it may be 'harvested' by data aggregator services. This enables linking of the archive record with other, perhaps not structurally related, published literature. Perhaps more importantly it notifies those monitoring the archive that a new entry is available, hence the CSD may automatically download the structural data and assimilate it into the database. This will return a deposition number which, along with any future literature citations of this entry, can be retrospectively added to the record to link the data or information sources.
eCrystallographyDataReports are intended for the publication of data only. Hence the results of a crystal structure determination may be disseminated in a manner that anyone wishing to utilise the information may access the entire archive of data related to it and assess its validity and worth. The archive entry can then be referenced, which allows learned society journals to streamline articles to contain more intellectual discussion and less experimental reports. This archive software is to be freely available for public download and installation and is simple and inexpensive to set up and maintain
Summer days in America [a trip to the mountains and lakes by rail, river and road]
No full textAn account of a trip along the Hudson, Niagara, St. Lawrence and Saguenay rivers, in New York State and Canada.Includes advertising matter."Printed for the author."Mode of access: Internet
Summer days in America; a trip through the Canadian rockies to Alaska.
No full textMode of access: Internet
Imaging using long range dipolar field effects
No full textThe work in this thesis has been undertaken by the author, except where indicated in reference, within the Magnetic Resonance Centre, at the University of Nottingham during the period from October 1998 to March 2001. This thesis details the different characteristics of the long range dipolar field and its application to magnetic resonance imaging. The long range dipolar field is usually neglected in nuclear magnetic resonance experiments, as molecular tumbling decouples its effect at short distances. However, in highly polarised samples residual long range components have a significant effect on the evolution of the magnetisation, giving rise to multiple spin echoes and unexpected quantum coherences. Three applications utilising these dipolar field effects are documented in this thesis. The first demonstrates the spatial sensitivity of the signal generated via dipolar field effects in structured liquid state samples. The second utilises the signal produced by the dipolar field to create proton spin density maps. These maps directly yield an absolute value for the water content of the sample that is unaffected by relaxation and any RF inhomogeneity or calibration errors in the radio frequency pulses applied. It has also been suggested that the signal generated by dipolar field effects may provide novel contrast in functional magnetic resonance imaging. In the third application, the effects of microscopic susceptibility variation on the signal are studied and the relaxation rate of the signal is compared to that of a conventional spin echo. (author)SIGLEAvailable from British Library Document Supply Centre- DSC:DXN058972 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
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