FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Preventive medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback

Background Interventions to improve delivery of preventive medical services have been shown to be effective in North America and the UK. However, there are few studies of the extent to which the impact of such interventions has been sustained, or of the impact of such interventions in disadvantaged populations or remote settings. This paper describes the trends in delivery of preventive medical services following a multifaceted intervention in remote community health centres in the Northern Territory of Australia. Methods The intervention comprised the development and dissemination of best practice guidelines supported by an electronic client register, recall and reminder systems and associated staff training, and audit and feedback. Clinical records in seven community health centres were audited at regular intervals against best practice guidelines over a period of three years, with feedback of audit findings to health centre staff and management. Results Levels of service delivery varied between services and between communities. There was an initial improvement in service levels for most services following the intervention, but improvements were in general not fully sustained over the three year period. Conclusions Improvements in service delivery are consistent with the international experience, although baseline and follow-up levels are in many cases higher than reported for comparable studies in North America and the UK. Sustainability of improvements may be achieved by institutionalisation of relevant work practices and enhanced health centre capacity

Projective dynamics and first integrals

We present the theory of tensors with Young tableau symmetry as an efficient computational tool in dealing with the polynomial first integrals of a natural system in classical mechanics. We relate a special kind of such first integrals, already studied by Lundmark, to Beltrami's theorem about projectively flat Riemannian manifolds. We set the ground for a new and simple theory of the integrable systems having only quadratic first integrals. This theory begins with two centered quadrics related by central projection, each quadric being a model of a space of constant curvature. Finally, we present an extension of these models to the case of degenerate quadratic forms.Comment: 39 pages, 2 figure

Using the past to constrain the future: how the palaeorecord can improve estimates of global warming

Climate sensitivity is defined as the change in global mean equilibrium temperature after a doubling of atmospheric CO2 concentration and provides a simple measure of global warming. An early estimate of climate sensitivity, 1.5-4.5{\deg}C, has changed little subsequently, including the latest assessment by the Intergovernmental Panel on Climate Change. The persistence of such large uncertainties in this simple measure casts doubt on our understanding of the mechanisms of climate change and our ability to predict the response of the climate system to future perturbations. This has motivated continued attempts to constrain the range with climate data, alone or in conjunction with models. The majority of studies use data from the instrumental period (post-1850) but recent work has made use of information about the large climate changes experienced in the geological past. In this review, we first outline approaches that estimate climate sensitivity using instrumental climate observations and then summarise attempts to use the record of climate change on geological timescales. We examine the limitations of these studies and suggest ways in which the power of the palaeoclimate record could be better used to reduce uncertainties in our predictions of climate sensitivity.Comment: The final, definitive version of this paper has been published in Progress in Physical Geography, 31(5), 2007 by SAGE Publications Ltd, All rights reserved. \c{opyright} 2007 Edwards, Crucifix and Harriso

Measurement of the rate of nu_e + d --> p + p + e^- interactions produced by 8B solar neutrinos at the Sudbury Neutrino Observatory

Solar neutrinos from the decay of $^8$B have been detected at the Sudbury Neutrino Observatory (SNO) via the charged current (CC) reaction on deuterium and by the elastic scattering (ES) of electrons. The CC reaction is sensitive exclusively to nu_e's, while the ES reaction also has a small sensitivity to nu_mu's and nu_tau's. The flux of nu_e's from ^8B decay measured by the CC reaction rate is \phi^CC(nu_e) = 1.75 +/- 0.07 (stat)+0.12/-0.11 (sys.) +/- 0.05(theor) x 10^6 /cm^2 s. Assuming no flavor transformation, the flux inferred from the ES reaction rate is \phi^ES(nu_x) = 2.39+/-0.34 (stat.)+0.16}/-0.14 (sys) x 10^6 /cm^2 s. Comparison of \phi^CC(nu_e) to the Super-Kamiokande Collaboration's precision value of \phi^ES(\nu_x) yields a 3.3 sigma difference, providing evidence that there is a non-electron flavor active neutrino component in the solar flux. The total flux of active ^8B neutrinos is thus determined to be 5.44 +/-0.99 x 10^6/cm^2 s, in close agreement with the predictions of solar models.Comment: 6 pages (LaTex), 3 figures, submitted to Phys. Rev. Letter

Differential Production Cross Section of Z Bosons as a Function of Transverse Momentum at sqrt{s}=1.8 TeV

We present a measurement of the transverse momentum distribution of Z bosons produced in ppbar collisions at sqrt{s}=1.8 TeV using data collected by the D0 experiment at the Fermilab Tevatron Collider during 1994--1996. We find good agreement between our data and a current resummation calculation. We also use our data to extract values of the non-perturbative parameters for a particular version of the resummation formalism, obtaining significantly more precise values than previous determinations.Comment: 10 pages, 2 figures, submitted to Phys. Rev. Letters v2 has margin error correcte

Hypericum perforatum plant cells reduce Agrobacterium viability during co-cultivation

Plant recalcitrance is the major barrier in developing Agrobacterium-mediated transformation protocols for several important plant species. Despite the substantial knowledge of T-DNA transfer process, very little is known about the factors leading to the plant recalcitrance. Here, we analyzed the basis of Hypericum perforatum L. (HP) recalcitrance to Agrobacterium-mediated transformation using cell suspension culture. When challenged with Agrobacterium, HP cells swiftly produced an intense oxidative burst, a typical reaction of plant defense. Agrobacterium viability started to decline and reached 99% mortality within 12 h, while the plant cells did not suffer apoptotic process. This is the first evidence showing that the reduction of Agrobacterium viability during co-cultivation with recalcitrant plant cells can affect transformation

Search for bottom squarks in pbarp collisions at sqrt(s)=1.8 TeV

We report on a search for bottom squarks produced in pbarp collisions at sqrt(s) = 1.8 TeV using the D0 detector at Fermilab. Bottom squarks are assumed to be produced in pairs and to decay to the lightest supersymmetric particle (LSP) and a b quark with branching fraction of 100%. The LSP is assumed to be the lightest neutralino and stable. We set limits on the production cross section as a function of bottom squark mass and LSP mass.Comment: 5 pages, Latex. submitted 3-12-1999 to PRD - Rapid Communicatio