New higher-order transition in causal dynamical triangulations

We reinvestigate the recently discovered bifurcation phase transition in Causal Dynamical Triangulations (CDT) and provide further evidence that it is a higher order transition. We also investigate the impact of introducing matter in the form of massless scalar fields to CDT. We discuss the impact of scalar fields on the measured spatial volumes and fluctuation profiles in addition to analysing how the scalar fields influence the position of the bifurcation transition.Comment: 15 pages, 11 figures. Conforms with version accepted for publication in Phys. Rev.

On the top eigenvalue of heavy-tailed random matrices

We study the statistics of the largest eigenvalue lambda_max of N x N random matrices with unit variance, but power-law distributed entries, P(M_{ij})~ |M_{ij}|^{-1-mu}. When mu > 4, lambda_max converges to 2 with Tracy-Widom fluctuations of order N^{-2/3}. When mu < 4, lambda_max is of order N^{2/mu-1/2} and is governed by Fr\'echet statistics. The marginal case mu=4 provides a new class of limiting distribution that we compute explicitely. We extend these results to sample covariance matrices, and show that extreme events may cause the largest eigenvalue to significantly exceed the Marcenko-Pastur edge. Connections with Directed Polymers are briefly discussed.Comment: 4 pages, 2 figure

D3 instantons in Calabi-Yau orientifolds with(out) fluxes

We investigate the instanton effect due to D3 branes wrapping a four-cycle in a Calabi-Yau orientifold with D7 branes. We study the condition for the nonzero superpotentials from the D3 instantons. For that matter we work out the zero mode structures of D3 branes wrapping a four-cycle both in the presence of the fluxes and in the absence of the fluxes. In the presence of the fluxes, the condition for the nonzero superpotential could be different from that without the fluxes. We explicitly work out a simple example of the orientifold of $K3 \times T^2/Z_2$ with a suitable flux to show such behavior. The effects of D3-D7 sectors are interesting and give further constraints for the nonzero superpotential. In a special configuration where D3 branes and D7 branes wrap the same four-cycle, multi-instanton calculus of D3 branes could be reduced to that of a suitable field theory. The structure of D5 instantons in Type I theory is briefly discussed.Comment: 17 pages; Typos corrected, arguments improved and references adde

Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m7 guanosine cap

In eukaryotes the majority of mRNAs have an m7G cap that is added cotranscriptionally and that plays an important role in many aspects of mRNA metabolism. The nuclear cap-binding complex (CBC; consisting of CBP20 and CBP80) mediates the stimulatory functions of the cap in pre-mRNA splicing, 3' end formation, and U snRNA export. As little is known about how nuclear CBC mediates the effects of the cap in higher eukaryotes, we have characterized proteins that interact with CBC in HeLa cell nuclear extracts as potential mediators of its function. Using cross-linking and coimmunoprecipitation, we show that eukaryotic translation initiation factor 4G (eIF4G), in addition to its function in the cytoplasm, is a nuclear CBC-interacting protein. We demonstrate that eIF4G interacts with CBC in vitro and that, in addition to its cytoplasmic localization, there is a significant nuclear pool of eIF4G in mammalian cells in vivo. Immunoprecipitation experiments suggest that, in contrast to the cytoplasmic pool, much of the nuclear eIF4G is not associated with eIF4E (translation cap binding protein of eIF4F) but is associated with CBC. While eIF4G stably associates with spliceosomes in vitro and shows close association with spliceosomal snRNPs and splicing factors in vivo, depletion studies show that it does not participate directly in the splicing reaction. Taken together the data indicate that nuclear eIF4G may be recruited to pre-mRNAs via its interaction with CBC and accompanies the mRNA to the cytoplasm, facilitating the switching of CBC for eIF4F. This may provide a mechanism to couple nuclear and cytoplasmic functions of the mRNA cap structure

Racetrack Inflation

We develop a model of eternal topological inflation using a racetrack potential within the context of type IIB string theory with KKLT volume stabilization. The inflaton field is the imaginary part of the K\"ahler structure modulus, which is an axion-like field in the 4D effective field theory. This model does not require moving branes, and in this sense it is simpler than other models of string theory inflation. Contrary to single-exponential models, the structure of the potential in this example allows for the existence of saddle points between two degenerate local minima for which the slow-roll conditions can be satisfied in a particular range of parameter space. We conjecture that this type of inflation should be present in more general realizations of the modular landscape. We also consider `irrational' models having a dense set of minima, and discuss their possible relevance for the cosmological constant problem.Comment: 23 pages 7 figures. The final version with minor modifications, to appear in JHE

Single Bead Affinity Detection (SINBAD) for the Analysis of Protein-Protein Interactions

We present a miniaturized pull-down method for the detection of protein-protein interactions using standard affinity chromatography reagents. Binding events between different proteins, which are color-coded with quantum dots (QDs), are visualized on single affinity chromatography beads by fluorescence microscopy. The use of QDs for single molecule detection allows the simultaneous analysis of multiple protein-protein binding events and reduces the amount of time and material needed to perform a pull-down experiment

Nuclear localised more sulphur accumulation1 epigenetically regulates sulphur homeostasis in Arabidopsis thaliana

Sulphur (S) is an essential element for all living organisms. The uptake, assimilation and metabolism of S in plants are well studied. However, the regulation of S homeostasis remains largely unknown. Here, we report on the identification and characterisation of the more sulphur accumulation1 (msa1-1) mutant. The MSA1 protein is localized to the nucleus and is required for both S adenosylmethionine (SAM) production and DNA methylation. Loss of function of the nuclear localised MSA1 leads to a reduction in SAM in roots and a strong S-deficiency response even at ample S supply, causing an over- accumulation of sulphate, sulphite, cysteine and glutathione. Supplementation with SAM suppresses this high S phenotype. Furthermore, mutation of MSA1 affects genome-wide DNA methylation, including the methylation of S-deficiency responsive genes. Elevated S accumulation in msa1-1 requires the increased expression of the sulphate transporter genes SULTR1;1 and SULTR1;2 which are also differentially methylated in msa1-1. Our results suggest a novel function for MSA1 in the nucleus in regulating SAM biosynthesis and maintaining S homeostasis epigenetically via DNA methylation

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein

Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 expression with relevance to different molecular classes of BC and patients’ outcome. The expression of RAD51 was assessed immunohistochemically in a well-characterised annotated series (n = 1184) of early-stage invasive BC with long-term follow-up. A subset of cases of BC from patients with known BRCA1 germline mutations was included as a control group. The results were correlated with clinicopathological and molecular parameters and patients’ outcome. RAD51 protein expression level was also assayed in a panel of cell lines using reverse phase protein array (RPPA). RAD51 was expressed in the nuclei (N) and cytoplasm (C) of malignant cells. Subcellular colocalisation phenotypes of RAD51 were significantly associated with clinicopathological features and patient outcome. Cytoplasmic expression (RAD51C+) and lack of nuclear expression (RAD51 N-) were associated with features of aggressive behaviour, including larger tumour size, high grade, lymph nodal metastasis, basal-like, and triple-negative phenotypes, together with aberrant expression of key DDR biomarkers including BRCA1. All BRCA1-mutated tumours had RAD51C+/N- phenotype. RPPA confirmed IHC results and showed differential expression of RAD51 in cell lines based on ER expression and BRCA1 status. RAD51 N+ and RAD51C+ tumours were associated with longer and shorter breast cancer-specific survival (BCSS), respectively. The RAD51 N+ was an independent predictor of longer BCSS (P<0.0001). Lack of RAD51 nuclear expression is associated with poor prognostic parameters and shorter survival in invasive BC patients. The significant associations between RAD51 subcellular localisation and clinicopathological features, molecular subtype and patients’ outcome suggest that the trafficking of DDR proteins between the nucleus and cytoplasm might play a role in the development and progression of BC

Enhanced production of multi-strange hadrons in high-multiplicity proton-proton collisions

At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark-gluon plasma (QGP)(1). Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed(2-6). Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions(7), is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton-proton (pp) collisions(8,9), but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton-proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p-Pb collision results(10,11), indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb-Pb collisions, where a QGP is formed.Peer reviewe