Block-Spin Approach to Electron Correlations

We consider an expansion of the ground state wavefunction of quantum lattice many-body systems in a basis whose states are tensor products of block-spin wavefunctions. We demonstrate by applying the method to the antiferromagnetic spin-1/2 chain that by selecting the most important many-body states the technique affords a severe truncation of the Hilbert space while maintaining high accuracy.Comment: 17 pages, 3 Postscript figure

Modelling ponatinib resistance in tyrosine kinase inhibitor-naive and dasatinib resistant BCR-ABL1+ cell lines

TKI resistance remains a major impediment to successful treatment of CML. In this study, we investigated the emerging modes of ponatinib resistance in TKI-naïve and dasatinib resistant BCR-ABL1+ cell lines. To investigate potential resistance mechanisms, ponatinib resistance was generated in BCR-ABL1+ cell-lines by long-term exposure to increasing concentrations of ponatinib. Two cell lines with prior dasatinib resistance demonstrated BCR-ABL1 kinase domain (KD) mutation(s) upon exposure to ponatinib. In one of these cell lines the T315I mutation had emerged during dasatinib exposure. When further cultured with ponatinib, the T315I mutation level and BCR-ABL1 mRNA expression level were increased. In the other cell line, compound mutations G250E/E255K developed with ponatinib exposure. In contrast, the ponatinib resistant cell lines that had no prior exposure to other TKIs (TKI-naïve) did not develop BCR-ABL1 KD mutations. Rather, both of these cell lines demonstrated Bcr-Abl-independent resistance via Axl overexpression. Axl, a receptor tyrosine kinase, has previously been associated with imatinib and nilotinib resistance. Ponatinib sensitivity was restored following Axl inhibition or shRNA-mediated-knockdown of Axl, suggesting that Axl was the primary driver of resistance and a potential target for therapy in this setting.Liu Lu, Chung Hoow Kok, Verity Ann Saunders, Jueqiong Wang, Jennifer Anne McLean, Timothy Peter Hughes, and Deborah Lee Whit

Isocurvature and Adiabatic Fluctuations of Axion in Chaotic Inflation Models and Large Scale Structure

In the chaotic inflation models, quantum fluctuations for axion fields lead to the overproduction of domain walls and too large isocurvature fluctuations which is inconsistent with the observations of cosmic microwave background anisotropies. These problems are solved by assuming a very flat potential for the Peccei-Quinn scalar. As the simplest possibility, we consider a model where the Peccei-Quinn scalar is an inflaton itself and show that the isocurvature fluctuations can be comparable with the adiabatic ones. We investigate cosmological implications in the case that both adiabatic and isocurvature fluctuations exist and find that the amplitude of the matter spectrum becomes smaller than that for the pure adiabatic case. This leads to relatively high bias parameter ($b \simeq 2$) which is favoured by the current observations.Comment: 5 pages, uudecoded postscript file with figure

UV and EUV Instruments

We describe telescopes and instruments that were developed and used for astronomical research in the ultraviolet (UV) and extreme ultraviolet (EUV) regions of the electromagnetic spectrum. The wavelength ranges covered by these bands are not uniquely defined. We use the following convention here: The EUV and UV span the regions ~100-912 and 912-3000 Angstroem respectively. The limitation between both ranges is a natural choice, because the hydrogen Lyman absorption edge is located at 912 Angstroem. At smaller wavelengths, astronomical sources are strongly absorbed by the interstellar medium. It also marks a technical limit, because telescopes and instruments are of different design. In the EUV range, the technology is strongly related to that utilized in X-ray astronomy, while in the UV range the instruments in many cases have their roots in optical astronomy. We will, therefore, describe the UV and EUV instruments in appropriate conciseness and refer to the respective chapters of this volume for more technical details.Comment: To appear in: Landolt-Boernstein, New Series VI/4A, Astronomy, Astrophysics, and Cosmology; Instruments and Methods, ed. J.E. Truemper, Springer-Verlag, Berlin, 201

BCR-ABL1 genomic DNA PCR response kinetics during first-line imatinib treatment of chronic myeloid leukemia

Accurate quantification of minimal residual disease during treatment of chronic myeloid leukaemia guides clinical decisions. The conventional minimal residual disease method, RQ-PCR for BCR-ABL1 mRNA, reflects a composite of the number of circulating leukemic cells and the BCR-ABL1 transcripts per cell. BCR-ABL1 genomic DNA only reflects leukemic cell number. We used both methods in parallel to determine the relative contribution of the leukemic cell number to molecular response. BCR-ABL1 DNA PCR and RQ-PCR were monitored up to 24 months in 516 paired samples from 59 newly-diagnosed patients treated with first-line imatinib in the TIDEL-II study. In the first 3 months of treatment BCR-ABL1 mRNA values declined more rapidly than DNA. By 6 months the two measures aligned closely. The expression of BCR-ABL1 mRNA was normalized to cell number to generate an expression ratio. The expression of e13a2 BCR-ABL1 was lower than that of e14a2 transcripts at multiple time points during treatment. BCR-ABL1 DNA was quantifiable in 48% of samples with undetectable BCR-ABL1 mRNA, resulting in minimal residual disease being quantifiable for an additional 5-18 months (median 12 months). These parallel studies show for the first time that the rapid decline in BCR-ABL1 mRNA over the first 3 months of treatment is due to a reduction in both cell number and transcript level per cell, whereas beyond 3 months falling levels of BCR-ABL1 mRNA are predominantly due to depletion of leukaemic cells.Ilaria S. Pagani, Phuong Dang, Ivar O. Kommers, Jarrad M. Goyne, Mario Nicola, Verity A. Saunders, Jodi Braley, Deborah L. White, David T. Yeung, Susan Branford, Timothy P. Hughes, and David M. Ros

DNA Damage Mediated S and G2 Checkpoints in Human Embryonal Carcinoma Cells

For mouse embryonic stem (ES) cells, the importance of the S and G2 cell cycle checkpoints for genomic integrity is increased by the absence of the G1 checkpoint. We have investigated ionizing radiation (IR)-mediated cell cycle checkpoints in undifferentiated and retinoic acid-differentiated human embryonal carcinoma (EC) cells. Like mouse ES cells, human EC cells did not undergo G1 arrest after IR but displayed a prominent S-phase delay followed by a G2-phase delay. In contrast, although differentiated EC cells also failed to arrest at G1-phase after IR, they quickly exited S-phase and arrested in G2-phase. In differentiated EC cells, the G2-M-phase cyclin B1/CDC2 complex was upregulated after IR, but the G1-S-phase cyclin E and the cyclin E/CDK2 complex were expressed at constitutively low levels, which could be an important factor distinguishing DNA damage responses between undifferentiated and differentiated EC cells. S-phase arrest and expression of p21 could be inhibited by 7-hydroxystaurosporine, suggesting that the ataxia-telangiectasia and Rad-3-related-checkpoint kinase 1 (ATR-CHK1), and p21 pathways might play a role in the IR-mediated S-phase checkpoint in EC cells. IR-mediated phosphorylation of ataxia-telangiectasia mutated, (CHK1), and checkpoint kinase 2 were distinctly higher in undifferentiated EC cells compared with differentiated EC cells. Combined with the prominent S and G2 checkpoints and a more efficient DNA damage repair system, these mechanisms operate together in the maintenance of genome stability for EC cells. Stem Cells 2009;27:568–57

Dialectics and difference: against Harvey's dialectical post-Marxism

David Harvey`s recent book, Justice, nature and the geography of difference (JNGD), engages with a central philosophical debate that continues to dominate human geography: the tension between the radical Marxist project of recent decades and the apparently disempowering relativism and `play of difference' of postmodern thought. In this book, Harvey continues to argue for a revised `post-Marxist' approach in human geography which remains based on Hegelian-Marxian principles of dialectical thought. This article develops a critique of that stance, drawing on the work of Jacques Derrida, Gilles Deleuze and Felix Guattari. I argue that dialectical thinking, as well as Harvey's version of `post-Marxism', has been undermined by the wide-ranging `post-' critique. I suggest that Harvey has failed to appreciate the full force of this critique and the implications it has for `post-Marxist' ontology and epistemology. I argue that `post-Marxism', along with much contemporary human geography, is constrained by an inflexible ontology which excessively prioritizes space in the theory produced, and which implements inflexible concepts. Instead, using the insights of several `post-' writers, I contend there is a need to develop an ontology of `context' leading to the production of `contextual theories'. Such theories utilize flexible concepts in a multilayered understanding of ontology and epistemology. I compare how an approach which produces a `contextual theory' might lead to more politically empowering theory than `post-Marxism' with reference to one of Harvey's case studies in JNGD

Large Scale Structure and Supersymmetric Inflation without Fine Tuning

We explore constraints on the spectral index $n$ of density fluctuations and the neutrino energy density fraction $\Omega_{HDM}$, employing data from a variety of large scale observations. The best fits occur for $n\approx 1$ and $\Omega_{HDM} \approx 0.15 - 0.30$, over a range of Hubble constants $40-60$ km s$^{-1}$ Mpc$^{-1}$. We present a new class of inflationary models based on realistic supersymmetric grand unified theories which do not have the usual `fine tuning' problems. The amplitude of primordial density fluctuations, in particular, is found to be proportional to $(M_X /M_P)^2$, where $M_X (M_P)$ denote the GUT (Planck) scale, which is reminiscent of cosmic strings! The spectral index $n = 0.98$, in excellent agreement with the observations provided the dark matter is a mixture of `cold' and `hot' components.Comment: LaTEX, 14 pp. + 1 postscript figure appende

Analysis of recent eta photoproduction data

Recent data on eta-meson photoproduction off a proton target in the energy range 2 < sqrt{s} < 3 GeV are analyzed with regard to their overall consistency. Results from the ELSA and CLAS measurements are compared with predictions of a Regge model whose reaction amplitude was fixed via a global fit to pre-2000 measurements of differential cross sections and polarization observables for gamma p -> eta p at higher energies. We find that all recent experimental results on differential cross sections for eta-meson photoproduction are in good agreement with each other, except for the CLAS data from 2009. However, the latter can be made consistent with the other data at the expense of introducing an energy-dependent renormalization factor. We point out that there indications in the data for a possible excitation of baryon resonances with masses around 2.1 and 2.4 GeV.Comment: 13 pages, 13 figures; small modifications in the text, some figures are improved, accepted for publication by Eur. Phys. J.

Piecewise Approximate Bayesian Computation: fast inference for discretely observed Markov models using a factorised posterior distribution

Many modern statistical applications involve inference for complicated stochastic models for which the likelihood function is difficult or even impossible to calculate, and hence conventional likelihood-based inferential techniques cannot be used. In such settings, Bayesian inference can be performed using Approximate Bayesian Computation (ABC). However, in spite of many recent developments to ABC methodology, in many applications the computational cost of ABC necessitates the choice of summary statistics and tolerances that can potentially severely bias the estimate of the posterior. We propose a new “piecewise” ABC approach suitable for discretely observed Markov models that involves writing the posterior density of the parameters as a product of factors, each a function of only a subset of the data, and then using ABC within each factor. The approach has the advantage of side-stepping the need to choose a summary statistic and it enables a stringent tolerance to be set, making the posterior “less approximate”. We investigate two methods for estimating the posterior density based on ABC samples for each of the factors: the first is to use a Gaussian approximation for each factor, and the second is to use a kernel density estimate. Both methods have their merits. The Gaussian approximation is simple, fast, and probably adequate for many applications. On the other hand, using instead a kernel density estimate has the benefit of consistently estimating the true piecewise ABC posterior as the number of ABC samples tends to infinity. We illustrate the piecewise ABC approach with four examples; in each case, the approach offers fast and accurate inference