Instability of supersymmetric microstate geometries

We investigate the classical stability of supersymmetric, asymptotically flat, microstate geometries with five non-compact dimensions. Such geometries admit an "evanescent ergosurface": a timelike hypersurface of infinite redshift. On such a surface, there are null geodesics with zero energy relative to infinity. These geodesics are stably trapped in the potential well near the ergosurface. We present a heuristic argument indicating that this feature is likely to lead to a nonlinear instability of these solutions. We argue that the precursor of such an instability can be seen in the behaviour of linear perturbations: nonlinear stability would require that all linear perturbations decay sufficiently rapidly but the stable trapping implies that some linear perturbation decay very slowly. We study this in detail for the most symmetric microstate geometries. By constructing quasinormal modes of these geometries we show that generic linear perturbations decay slower than any inverse power of time.This work was supported by European Research Council grant ERC-2011-StG279363-HiDGR.This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/JHEP10(2016)03

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

The Escherichia coli transcriptome mostly consists of independently regulated modules

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome

Ultraspinning instability: the missing link

We study linearized perturbations of Myers-Perry black holes in d=7, with two of the three angular momenta set to be equal, and show that instabilities always appear before extremality. Analogous results are expected for all higher odd d. We determine numerically the stationary perturbations that mark the onset of instability for the modes that preserve the isometries of the background. The onset is continuously connected between the previously studied sectors of solutions with a single angular momentum and solutions with all angular momenta equal. This shows that the near-extremality instabilities are of the same nature as the ultraspinning instability of d>5 singly-spinning solutions, for which the angular momentum is unbounded. Our results raise the question of whether there are any extremal Myers-Perry black holes which are stable in d>5.Comment: 19 pages. 1 figur

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Ultraspinning instability of anti-de Sitter black holes

Myers-Perry black holes with a single spin in d>5 have been shown to be unstable if rotating sufficiently rapidly. We extend the numerical analysis which allowed for that result to the asymptotically AdS case. We determine numerically the stationary perturbations that mark the onset of the instabilities for the modes that preserve the rotational symmetries of the background. The parameter space of solutions is thoroughly analysed, and the onset of the instabilities is obtained as a function of the cosmological constant. Each of these perturbations has been conjectured to represent a bifurcation point to a new phase of stationary AdS black holes, and this is consistent with our results.Comment: 22 pages, 7 figures. v2: Reference added. Matches published versio

Balanço e análise da sustentabilidade energética na produção orgânica de hortaliças.

Os insumos e serviços utilizados na produção vegetal representam custo energético. Dependendo desses fatores e das produtividades obtidas, a conversão da produção em energia determinará a eficiência energética do sistema. A agricultura orgânica somente atingirá a missão de preservação ambiental se tiver comprovada sustentabilidade energética. Neste trabalho, objetivou-se caracterizar os balanços energéticos dos cultivos orgânicos e analisar sua sustentabilidade, em comparação aos sistemas convencionais. Monitoraram-se campos de produção de dez culturas, de 1991 a 2000 em Domingos Martins-ES. Os dados do sistema convencional foram obtidos pelas médias dos coeficientes técnicos da região. Quantificaram-se os coeficientes técnicos, convertendo suas grandezas físicas em equivalentes energéticos, expressos em kcal. O sistema orgânico gastou 4.571.159 kcal ha-1 e apresentou 12.696.712 kcal ha-1 de energia inserida na colheita, mostrando balanço médio de 2,78. Esse valor foi similar ao obtido no sistema convencional (1,93). As participações dos componentes nos gastos do sistema orgânico foram embalagem (35,8%), composto orgânico (17,2%), irrigação (12,6%), sementes/mudas (12,4%) e mão-de-obra (11,0%), serviços mecânicos (5,0%) e frete (4,5%). Se os custos com embalagens fossem eliminados, os gastos do sistema orgânico seriam reduzidos para 2.930.113 kcal ha-1, aumentando sua eficiência. A maioria dos cultivos orgânicos pode ser considerada sustentável em transformação de energia, com balanços superiores a 1,00 e produção média diária de 80.421 kcal ha-1 por dia, superior à necessidade mínima de 58.064 kcal ha-1

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector