Oncometabolites: tailoring our genes

Increased glucose metabolism in cancer cells is a phenomenon that has been known for over 90 years, allowing maximal cell growth through faster ATP production and redistribution of carbons towards nucleotide, protein and fatty acid synthesis. Recently, metabolites that can promote tumorigeneis by altering the epigenome have been identified. These ‘oncometabolites’ include the tricarboxylic acid cycle metabolites succinate and fumarate, whose levels are elevated in rare tumours with succinate dehydrogenase and fumarate hydratase mutations, respectively. 2-Hydroxyglutarate is another oncometabolite; it is produced de novo as a result of the mutation of isocitrate dehydrogenase, and is commonly found in gliomas and acute myeloid leukaemia. Interestingly, the structural similarity of these oncometabolites to their precursor metabolite, α-ketoglutarate, explains the tumorigenic potential of these metabolites, by competitive inhibition of a superfamily of enzymes called the α-ketoglutarate-dependent dioxygenases. These enzymes utilize α-ketoglutarate as a cosubstrate, and are involved in fatty acid metabolism, oxygen sensing, collagen biosynthesis, and modulation of the epigenome. They include enzymes that are involved in regulating gene expression via DNA and histone tail demethylation. In this review, we will focus on the link between metabolism and epigenetics, and how we may target oncometabolite-induced tumorigenesis in the future

On the massive gluon propagator, the PT-BFM scheme and the low-momentum behaviour of decoupling and scaling DSE solutions

We study the low-momentum behaviour of Yang-Mills propagators obtained from Landau-gauge Dyson-Schwinger equations (DSE) in the PT-BFM scheme. We compare the ghost propagator numerical results with the analytical ones obtained by analyzing the low-momentum behaviour of the ghost propagator DSE in Landau gauge, assuming for the truncation a constant ghost-gluon vertex and a simple model for a massive gluon propagator. The asymptotic expression obtained for the regular or decoupling ghost dressing function up to the order ${\cal O}(q^2)$ is proven to fit pretty well the numerical PT-BFM results. Furthermore, when the size of the coupling renormalized at some scale approaches some critical value, the numerical PT-BFM propagators tend to behave as the scaling ones. We also show that the scaling solution, implying a diverging ghost dressing function, cannot be a DSE solution in the PT-BFM scheme but an unattainable limiting case.Comment: 16 pages, 2 figs., 2 tabs (updated version to be published in JHEP

Analisis Kepuasan Wajib Pajak: Pendekatan Terhadappenggunaan Teknologi Informasi Dan Self Assessment

The aim of this study is to investigate the influence of using Information technology and self assessment system to tax prayers' Satisfaction. The Hypothesis which have been formulated in this research are: there is direct and indirect influence of using Information technology and self assessment system to tax prayer's Satisfaction. The research is a survey to tax payers in Surakarta, Data have been collected with quesionaries as 100 respondents are processed with, validity and reliability test, the regression analysis, t test, F test and test of R2. Keyword: using Information technology, self assessment system, tax prayers Satisfaction

Protecting migrant children’s rights

This report relates to the training workshop on the protection of migrant children’s rights which is part of an ESRC-funded research project currently led by Dr Ana Beduschi (https://migrantchildren.org/). The event was organised by the University of Exeter in partnership with the NGO Network for Children’s Rights Greece. The workshop was held at their headquarters in Athens on the 28 January 2017. Agenda and training materials (in English and in Greek) available here: https://migrantchildren.org/2016/10/25/upcoming-in-january-2017/ The event was attended by aid workers (frontline workers) providing services in three refugee camps in Athens and by refugee lawyers working for the Network for Children’s Rights and for ARSIS (Greek NGO providing support for children). This workshop emphasised training on legal aspects of the protection of migrant children. It also explored the possibility of developing a vulnerability and best interests tool which would be simple and accessible to frontline workers. Despite the absence of specific official procedure, frontline workers at the NGO Network for Children’s Rights are already conducting a form of best interests of the child determinations in relation to migrant children. Following the workshop and considering their input, we propose a vulnerability and best interests of the child determination tool, which can be used by frontline workers in their daily work.ESRC IAA Project Co-Creation Fun

Protecting migrant children’s rights

This report relates to the training workshop on the protection of migrant children’s rights which is part of an ESRC-funded research project currently led by Dr Ana Beduschi (https://migrantchildren.org/). The event was organised by the University of Exeter in partnership with the NGO Network for Children’s Rights Greece. The workshop was held at their headquarters in Athens on the 28 January 2017. Agenda and training materials (in English and in Greek) available here: https://migrantchildren.org/2016/10/25/upcoming-in-january-2017/ The event was attended by aid workers (frontline workers) providing services in three refugee camps in Athens and by refugee lawyers working for the Network for Children’s Rights and for ARSIS (Greek NGO providing support for children). This workshop emphasised training on legal aspects of the protection of migrant children. It also explored the possibility of developing a vulnerability and best interests tool which would be simple and accessible to frontline workers. Despite the absence of specific official procedure, frontline workers at the NGO Network for Children’s Rights are already conducting a form of best interests of the child determinations in relation to migrant children. Following the workshop and considering their input, we propose a vulnerability and best interests of the child determination tool, which can be used by frontline workers in their daily work.ESRC IAA Project Co-Creation Fun

Seismological constraints on the down-dip shape of normal faults

We present a seismological technique for determining the down-dip shape of seismogenic normal faults. Synthetic models of non-planar source geometries reveal the important signals in teleseismic P and SH waveforms that are diagnostic of down-dip curvature. In particular, along-strike SH waveforms are the most sensitive to variations in source geometry, and have significantly more complex and larger-amplitude waveforms for curved source geometries than planar ones. We present the results of our forward-modelling technique for 13 earthquakes. Most continental normal-faulting earthquakes that rupture through the full seismogenic layer are planar and have dips of 30°–60°. There is evidence for faults with a listric shape from some of the earthquakes occurring in two regions; Tibet and East Africa. These ruptures occurred on antithetic faults, or minor faults within the hanging walls of the rifts affected, which may suggest a reason for the down-dip curvature. For these earthquakes, the change in dip across the seismogenic part of the fault plane is ≤30°.This work forms part of the NERC- and ESRC-funded project ‘Earthquakes without Frontiers’ and was partially supported by the NERC large grant ‘Looking inside the Continents from Space’

Bayesian network structure learning with causal effects in the presence of latent variables.

Latent variables may lead to spurious relationships that can be misinterpreted as causal relationships. In Bayesian Networks (BNs), this challenge is known as learning under causal insufficiency. Structure learning algorithms that assume causal insufficiency tend to reconstruct the ancestral graph of a BN, where bi-directed edges represent confounding and directed edges represent direct or ancestral relationships. This paper describes a hybrid structure learning algorithm, called CCHM, which combines the constraint-based part of cFCI with hill-climbing score-based learning. The score-based process incorporates Pearl s do-calculus to measure causal effects and orientate edges that would otherwise remain undirected, under the assumption the BN is a linear Structure Equation Model where data follow a multivariate Gaussian distribution. Experiments based on both randomised and well-known networks show that CCHM improves the state-of-the-art in terms of reconstructing the true ancestral graph

Simulating the Hot X-ray Emitting Gas in Elliptical Galaxies

We study the chemo-dynamical evolution of elliptical galaxies and their hot X-ray emitting gas using high-resolution cosmological simulations. Our Tree N-body/SPH code includes a self-consistent treatment of radiative cooling, star formation, supernovae feedback, and chemical enrichment. We present a series of LCDM cosmological simulations which trace the spatial and temporal evolution of heavy element abundance patterns in both the stellar and gas components of galaxies. X-ray spectra of the hot gas are constructed via the use of the vmekal plasma model, and analysed using XSPEC with the XMM EPN response function. Simulation end-products are quantitatively compared with the observational data in both the X-ray and optical regime. We find that radiative cooling is important to interpret the observed X-ray luminosity, temperature, and metallicity of the interstellar medium of elliptical galaxies. However, this cooled gas also leads to excessive star formation at low redshift, and therefore results in underlying galactic stellar populations which are too blue with respect to observations.Comment: 6 pages, 3 figures, to appear in the proceedings of "The IGM/Galaxy Connection - The Distribution of Baryons at z=0", ed. M. Putman & J. Rosenberg; High resolution version is available at http://astronomy.swin.edu.au/staff/dkawata/research/papers.htm