To investigate the fundamental question of how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we focused on nuclear growth in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days, and developed open-source tools for image and data analysis and an interactive timelapse viewer for exploring quantitative features of nuclear size and shape. We performed a data-driven analysis of nuclear growth variations across timescales.
View Article and Find Full Text PDFBackground: Evidence generation partnerships between researchers and policy-makers are a potential method for producing more relevant research with greater potential to impact on policy and practice. Little is known about how such partnerships are enacted in practice, however, or how to increase their effectiveness. We aimed to determine why researchers and policy-makers choose to work together, how they work together, which partnership models are most common, and what the key (1) relationship-based and (2) practical components of successful research partnerships are.
View Article and Find Full Text PDFBackground: Currently the uptake of the influenza vaccine amongst Australian hospital staff remains low. While some staff members choose not to receive the vaccine, others may feel decisional conflict around whether to receive the vaccine or not. Having access to information that is personalized to the staff members' concerns may alleviate this conflict.
View Article and Find Full Text PDFThis paper discusses an innovative learning approach in which people having experience of mental health services facilitated humanistic clinical supervision with groups of student nurses in the classroom. A four-day course of preparation for the role of supervisor is described and the results of subsequent clinical supervision sessions are analysed. Seven service users who had previous experience of teaching students in the classroom and fifty students on a Diploma/BSc in mental health nursing course participated in the project, which was evaluated through focus groups.
View Article and Find Full Text PDFDescribed is the construction of the N-methylwelwitindolinone C core via an efficient strategy that employs a sequential rhodium carbenoid-mediated O-H insertion, Claisen rearrangement and transannular [3+2] nitrone cycloaddition.
View Article and Find Full Text PDFThe role of specialist nurses in triage, diagnosis and management of emergency eye conditions is well established, and encouraging reports of the safety and effectiveness of such services have been published. Specialist nurses in an emergency eye clinic in the UK seeing >7000 patients per year had been found at initial evaluation to treat 22% of the 1976 patients seen over a three month period without referring on to an ophthalmologist. A repeat of this evaluation five years later found this proportion had dropped to 17% (chi(2) = 16.
View Article and Find Full Text PDFJ Psychiatr Ment Health Nurs
April 2009
Int J Palliat Nurs
November 2008
Developing accountable and appropriate care services depends on listening to the views of service users. This nurse-led, qualitative study explored 10 palliative care patients' views of their care in hospital and at home using non-standard interviews. A total of 10 categories emerged, some of which are not reflected well in extant literature.
View Article and Find Full Text PDFObjective: To determine the seroprevalence of hepatitis A, B and C and the prevalence of risk factors for blood-borne infections in persons subject to homelessness attending a medical clinic in inner Sydney.
Method: During 2003-05, 201 clients were enrolled in a prospective study to determine the acceptance, completion rates and immunogenicity of the standard vaccination schedule for hepatitis A and B. On enrolment, clients completed a risk factor assessment questionnaire and undertook pre-vaccination serological screening for hepatitis A, B and C.
Novel anthranilamides were surprisingly found to exert additional activity on B-RAF. Corresponding thiophene, pyrazole, and thiazole core analogs were prepared as VEGFR-2 inhibitors with c-KIT, and B-RAF activity. Compounds in the phenyl, thiophene, and thiazole series are in vivo active.
View Article and Find Full Text PDFPOEMS is an acronym for polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It is a poorly understood paraneoplastic syndrome that stems from an underlying plasma cell dyscrasia. Of the skin changes, the glomeruloid hemangioma is considered to be a specific marker of POEMS syndrome.
View Article and Find Full Text PDFA key step in homologous recombination is the loading of Rad51 onto single-stranded DNA to form a nucleoprotein filament that promotes homologous DNA pairing and strand exchange. Mediator proteins, such as Rad52 and Rad55-Rad57, are thought to aid filament assembly by overcoming an inhibitory effect of the single-stranded-DNA-binding protein replication protein A. Here we show that mediator proteins are also required to enable fission yeast Rad51 (called Rhp51) to function in the presence of the F-box DNA helicase Fbh1.
View Article and Find Full Text PDFSweet's syndrome is a neutrophilic dermatosis characterized by tender, erythematous, pseudovesicular plaques that can be associated with hematologic malignancy. We report a patient with recalcitrant Sweet's syndrome that preceded the development of myelodysplastic syndrome by 30 months. The delay between the onset of Sweet's syndrome and the subsequent diagnosis of myelodysplasia highlights the need for thorough and repeated evaluation for underlying malignancy in patients with such a course.
View Article and Find Full Text PDFExpert Opin Ther Pat
June 2005
Inhibition of vascular endothelial growth factor receptor (VEGFR) signalling, using either antibodies or small molecule inhibitors of the VEGFR kinase domain, has become a major area of research in oncology. The phthalazine PTK787/ZK222584, first published in the literature in 1998, is one of the most advanced VEGFR inhibitors in the clinic. This paper provides an update on the patenting activity related to the phthalazine class.
View Article and Find Full Text PDFNucleic Acids Res
February 2005
In budding yeast most Rad51-dependent and -independent recombination depends on Rad52. In contrast, its homologue in fission yeast, Rad22, was assumed to play a less critical role possibly due to functional redundancy with another Rad52-like protein Rti1. We show here that this is not the case.
View Article and Find Full Text PDFThe double Holliday junction (dHJ) is generally regarded to be a key intermediate of meiotic recombination, whose resolution is critical for the formation of crossover recombinants. In fission yeast, the Mus81-Eme1 endonuclease has been implicated in resolving dHJs. Consistent with this role, we show that Mus81-Eme1 is required for generating meiotic crossovers.
View Article and Find Full Text PDFThe blockage of replication forks can result in the disassembly of the replicative apparatus and reversal of the fork to form a DNA junction that must be processed in order for replication to restart and sister chromatids to segregate at mitosis. Fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4 are endonucleases that have been implicated in the processing of aberrant DNA junctions formed at stalled replication forks. Here we have investigated the activity of purified Mus81-Eme1 and Mus81-Mms4 on substrates that resemble DNA junctions that are expected to form when a replication fork reverses.
View Article and Find Full Text PDFThe processing of stalled replication forks and the repair of collapsed replication forks are essential functions in all organisms. In fission yeast DNA junctions at stalled replication forks appear to be processed by either the Rqh1 DNA helicase or Mus81-Eme1 endonuclease. Accordingly, we show that the hypersensitivity to agents that cause replication fork stalling of mus81, eme1, and rqh1 mutants is suppressed by a Holliday junction resolvase (RusA), as is the synthetic lethality of a mus81(-) rqh1(-) double mutant.
View Article and Find Full Text PDFAn asymmetric, tandem inter [4 + 2]/intra [3 + 2] bridged mode (beta-tether) cycloaddition of nitroalkenes has been developed. This new sequence involves the Lewis acid-promoted [4 + 2] cycloaddition of nitro olefins with enantiopure 1-alkoxy-1,4-dienes. The resulting nitronates, bearing a C(5) tethered dipolarophile, undergo thermal, intramolecular [3 + 2] cycloaddition to afford stable tricyclic nitroso acetals, which can be subsequently reduced to provide interesting aminocyclopentanes.
View Article and Find Full Text PDFA new variation of the tandem inter [4 + 2]/intra [3 + 2] cycloaddition of nitroalkenes has been developed. This method involves the Lewis acid-promoted [4 + 2] cycloaddition of nitro olefins 12 with 1-alkoxy-1,4-dienes 3. The resulting nitronates 13, bearing a C(5) tethered dipolarophile, undergo thermal, intramolecular [3 + 2] cycloaddition to afford stable tricyclic nitroso acetals 14, which can be subsequently reduced to unveil a new carbocycle 16.
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