Meningiomas occurring during long-term survival after treatment for childhood cancer

Childhood cancer is rare but improvements in treatment over the past five decades have resulted in a cohort of more than 30,000 long-term survivors of childhood cancer in the UK with more added annually. These long-term survivors are at risk of late effects of cancer treatment which replace original tumour recurrence as the leading cause of premature death. Second neoplasms are a particular risk and in the central nervous system meningiomas occur increasingly with increased radiation dose to central nervous system tissue and length of time after exposure, resulting in a 500-fold increase above that expected in the normal population by 40 years of follow up. This multidisciplinary author group and others met to discuss the issue. Our pooled information, and consensus that screening should only follow symptoms, was published online by the Royal College of Radiologists in 2013. We outline here the current knowledge and management of these neoplasms secondary to childhood cancer treatment

History of the abacus

As the revolution in computing advances, it is appropriate to step back and look at the earliest practical aid to computation?? abacus. Its formal western origins lie with the Greeks and the expansion of trade in the seventh century BC, and its design and application showed remarkably little change over the following two thousand years. A measure of the usefulness of the abacus is seen by the fact that it survived the advent of algorism by some six centuries but its major significance for western culture lies in its perfect and seminal representation of the decimal system

Regulation of the cardiomyocyte transcriptome vs translatome by endothelin-1 and insulin: translational regulation of 5' terminal oligopyrimidine tract (TOP) mRNAs by insulin

Background: Changes in cellular phenotype result from underlying changes in mRNA transcription and translation. Endothelin-1 stimulates cardiomyocyte hypertrophy with associated changes in mRNA/protein expression and an increase in the rate of protein synthesis. Insulin also increases the rate of translation but does not promote overt cardiomyocyte hypertrophy. One mechanism of translational regulation is through 5' terminal oligopyrimidine tracts (TOPs) that, in response to growth stimuli, promote mRNA recruitment to polysomes for increased translation. TOP mRNAs include those encoding ribosomal proteins, but the full panoply remains to be established. Here, we used microarrays to compare the effects of endothelin-1 and insulin on the global transcriptome of neonatal rat cardiomyocytes, and on mRNA recruitment to polysomes (i.e. the translatome). Results: Globally, endothelin-1 and insulin (1 h) promoted >1.5-fold significant (false discovery rate 1.25-fold significant changes in expression in total and/or polysomal RNA induced by endothelin-1 or insulin, respectively, of which ~35% of endothelin-1-responsive and ~56% of insulin-responsive transcripts were translationally regulated. Of mRNAs for established proteins recruited to polysomes in response to insulin, 49 were known TOP mRNAs with a further 15 probable/possible TOP mRNAs, but 49 had no identifiable TOP sequences or other consistent features in the 5' untranslated region. Conclusions: Endothelin-1, rather than insulin, substantially affects global transcript expression to promote cardiomyocyte hypertrophy. Effects on RNA recruitment to polysomes are subtle, with differential effects of endothelin-1 and insulin on specific transcripts. Furthermore, although insulin promotes recruitment of TOP mRNAs to cardiomyocyte polysomes, not all recruited mRNAs are TOP mRNAs

A dynamically extending exclusion process

An extension of the totally asymmetric exclusion process, which incorporates a dynamically extending lattice is explored. Although originally inspired as a model for filamentous fungal growth, here the dynamically extending exclusion process (DEEP) is studied in its own right, as a nontrivial addition to the class of nonequilibrium exclusion process models. Here we discuss various mean-field approximation schemes and elucidate the steady state behaviour of the model and its associated phase diagram. Of particular note is that the dynamics of the extending lattice leads to a new region in the phase diagram in which a shock discontinuity in the density travels forward with a velocity that is lower than the velocity of the tip of the lattice. Thus in this region the shock recedes from both boundaries.Comment: 20 pages, 12 figure

Efficiency, equality and labelling: an experimental investigation of focal points in explicit bargaining

Efficiency, equality and labelling: an experimental investigation of focal points in explicit bargainin

The Little Ice Age glacier maximum in Iceland and the North Atlantic Oscillation: evidence from Lambatungnajökull, southeast Iceland.

This article examines the link between late Holocene fluctuations of Lambatungnajokull, an outlet glacier of the Vatnajokull ice cap in Iceland, and variations in climate. Geomorphological evidence is used to reconstruct the pattern of glacier fluctuations, while lichenometry and tephrostratigraphy are used to date glacial landforms deposited over the past /400 years.Moraines dated using two different lichenometric techniques indicate that the most extensive period of glacier expansion occurred shortly before c. AD 1795, probably during the 1780s. Recession over the last 200 years was punctuated by re-advances in the 1810s, 1850s, 1870s, 1890s and c. 1920, 1930 and 1965. Lambatungnajokull receded more rapidly in the 1930s and 1940s than at any other time during the last 200 years. The rate and style of glacier retreat since 1930 compare well with other similar-sized, non-surging, glaciers in southeast Iceland, suggesting that the terminus fluctuations are climatically driven. Furthermore, the pattern of glacier fluctuations over the 20th century broadly reflects the temperature oscillations recorded at nearby meteorological stations. Much of the climatic variation experienced in southern Iceland, and the glacier fluctuations that result, can be explained by secular changes in the North Atlantic Oscillation (NAO). Advances of Lambatungnajokull generally occur during prolonged periods of negative NAO index. The main implication of this work relates to the exact timing of the Little Ice Age in the Northeast Atlantic. Mounting evidence now suggests that the period between AD 1750 and 1800, rather than the late 19th century, represented the culmination of the Little Ice Age in Iceland

Glycogen synthase kinases 3α and 3β in cardiac myocytes: regulation and consequences of their inhibition

Inhibition of glycogen synthase kinase 3β (GSK3β) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3α (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3β in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained

Endothelin-1, phorbol esters and phenylephrine stimulate MAP kinase activities in ventricular cardiomyocytes

AbstractET-1 stimulated MBP kinase activity in cultured cardiomyocytes. Maximal activation (3.5-fold) was at 5 min. EC50 was 0.2 nM. PMA or PE also increased MBP kinase (4- or 2.5-fold, respectively). Pre-treatment with PMA down-regulated the subsequent response to ET-1 or PMA. ET-1- or PMA-stimulated MBP kinase was resolved into 2 major (peaks II and IV) and 2 minor peaks by FPLC on Mono Q. Peaks II and IV were inactivated by either LAR or PP2A. Renatured MBP kinase activities following SDS-PAGE in MBP-containing gels and immunoblot analysis showed that peak II was a p42 MAP kinase and peak IV was a p44 MAP kinase

Landscape Evolution of the Dry Valleys, Transantarctic Mountains: Tectonic Implications

There are different views about the amount and timing of surface uplift in the Transantarctic Mountains and the geophysical mechanisms involved. Our new interpretation of the landscape evolution and tectonic history of the Dry Valleys area of the Transantarctic Mountains is based on geomorphic mapping of an area of 10,000 km(2). The landforms are dated mainly by their association with volcanic ashes and glaciomarine deposits and this permits a reconstruction of the stages and timing of landscape evolution. Following a lowering of base level about 55 m.y. ago, there was a phase of rapid denudation associated with planation and escarpment retreat, probably under semiarid conditions. Eventually, downcutting by rivers, aided in places by glaciers, graded valleys to near present sea level. The main valleys were flooded by the sea in the Miocene during a phase of subsidence before experiencing a final stage of modest upwarping near the coast. There has been remarkably little landform change under the stable, cold, polar conditions of the last 15 m.y. It is difficult to explain the Sirius Group deposits, which occur at high elevations in the area, if they are Pliocene in age. Overall, denudation may have removed a wedge of rock with a thickness of over 4 km at the coast declining to 1 km at a point 75 km inland, which is in good agreement with the results of existing apatite fission track analyses. It is suggested that denudation reflects the differences in base level caused by high elevation at the time of extension due to underplating and the subsequent role of thermal uplift and flexural isostasy. Most crustal uplift (2-4 km) is inferred to have occurred in the early Cenozoic with 400 m of subsidence in the Miocene followed by 300 m of uplift in the Pliocene

Nonequilibrium statistical physics applied to biophysical cellular processes

The methods of statistical physics are increasingly being employed in a range of interdisciplinary areas. In particular, aspects of complex biological processes have been elucidated by bringing the problems down to the level of simple interactions studied in a statistical sense. In nonequilibrium statistical physics, a one dimensional lattice model known as the totally asymmetric simple exclusion processes (TASEP) has become prominent as a tool for modelling various cellular transport processes. Indeed the context in which the TASEP was first introduced (MacDonald et. al., 1968) was to model ribosome motion along mRNA during protein synthesis. In this work I study a variation of the TASEP in which particles hop along a one dimensional lattice which extends as they reach the end. We introduce this model to describe the unique growth dynamics of filamentous fungi, whereby a narrow fungal filament extends purely from its tip region while being supplied with growth materials from behind the tip. We find that the steady state behaviour of our model reflects that of the TASEP, however there is an additional phase where a dynamic shock is present in the system. I show through Monte Carlo simulation and theoretical analysis that the qualitative behaviour of this model can be predicted with a simple mean-field approximation, while the details of the phase behaviour are accurate only in a refined approximation which takes into account some correlations. I also discuss a further refined mean-field approximation and give a heuristic argument for our results. Next I present an extension of the model which allows the particles to interact with a second lattice, on which they diffuse in either direction. A first order meanfield continuum approximation suggests that the steady states of this system will exhibit some novel behaviour. Through Monte Carlo simulation I discuss the qualitative changes that arise due to the on-off dynamics. Finally I study a model for a second biological phenomenon: the length fluctuations of microtubules. The model describes stochastic polymerisation events at the tip of a microtubule. Using a mean-field theory, we find a transition between regimes where the microtubule grows on average, and where the length remains finite. For low rates of polymerisation and depolymerisation, the transition is in good agreement with Monte Carlo simulation