1,009 research outputs found
Use of the reported Edmonton frail scale in the assessment of patients for transcatheter aortic valve replacement: a possible selection tool in very high-risk patients?
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
On the joint production of research and training
Universities and research institutions have the responsibility to produce science and to provide training to new generations of researchers. In this paper, we propose a model to analyze the determinants of a senior scientistâs decisions about allocating time between these tasks. The results of this decision depend upon the characteristics of the research project, the senior scientistâs concern for training and the expected innate ability of the junior scientist involved. We analyze the role that a regulator can play in defining both the value of scientific projects and the future population of independent scientists.info:eu-repo/semantics/publishedVersio
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Population-based emergence of unfamiliar climates
Time of emergence, which characterizes when significant signals of climate change will emerge from existing variability, is a useful and increasingly common metric. However, a more useful metric for understanding future climate change in the context of past experience may be the ratio of climate signal to noise (S/N)âa measure of the amplitude of change expressed in terms of units of existing variability. Here, we present S/N projections in the context of emergent climates (termed âunusualâ, âunfamiliarâ and âunknownâ by reference to an individualâs lifetime), highlighting sensitivity to future emissions scenarios and geographical and human groupings. We show how for large sections of the worldâs population, and for several geopolitical international groupings, mitigation can delay the onset of âunknownâ or âunfamiliarâ climates by decades, and perhaps even beyond 2100. Our results demonstrate that the benefits of mitigation accumulate over several decades, a key metric of which is reducing S/N, or keeping climate as familiar as possible. A relationship is also identified between cumulative emissions and patterns of emergent climate signals. Timely mitigation will therefore provide the greatest benefits to those facing the earliest impacts, many of whom are alive now
Energy cost and return for hunting in African wild dogs and Cheetahs
African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs
Optimal antiplatelet strategy after transcatheter aortic valve implantation: a meta-analysis
Objective International guidelines recommend the use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI). The recommended duration of DAPT varies between guidelines. In this two-part study, we (1) performed a structured survey of 45 TAVI centres from around the world to determine if there is consensus among clinicians regarding antiplatelet therapy after TAVI; and then (2) performed a systematic review of all suitable studies (randomised controlled trials (RCTs) and registries) to determine if aspirin monotherapy can be used instead of DAPT. Methods A structured electronic survey regarding antiplatelet use after TAVI was completed by 45 TAVI centres across Europe, Australasia and the USA. A systematic review of TAVI RCTs and registries was then performed comparing DAPT duration and incidence of stroke, bleeding and death. A variance weighted least squared metaregression was then performed to determine the relationship of antiplatelet therapy and adverse events. Results 82.2% of centres routinely used DAPT after TAVI. Median duration was 3 months. 13.3% based their practice on guidelines. 11â781 patients (26 studies) were eligible for the metaregression. There was no benefit of DAPT over aspirin monotherapy for stroke (P=0.49), death (P=0.72) or bleeding (P=0.91). Discussion Aspirin monotherapy appears to be as safe and effective as DAPT after TAVI
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
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 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
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