Large-scale structure and the redshift-distance relation

In efforts to demonstrate the linear Hubble law v = Hr from galaxy observations, the underlying simplicity is often obscured by complexities arising from magnitude-limited data. In this paper we point out a simple but previously unremarked fact: that the shapes and orientations of structures in redshift space contain in themselves independent information about the cosmological redshift-distance relation. The orientations of voids in the CfA slice support the Hubble law, giving a redshift-distance power index p = 0.83 +/- 0.36 (void data from Slezak, de Lapparent, & Bijoui 1993) or p = 0.99 +/- 0.38 (void data from Malik & Subramanian 1997).Comment: 11 pages (AASTeX), 4 figures, to appear in the Astrophysical Journal Letter

Constraints on Galaxy Bias, Matter Density, and Primordial Non--Gausianity from the PSCz Galaxy Redshift Survey

We compute the bispectrum for the \IRAS PSCz catalog and find that the galaxy distribution displays the characteristic signature of gravity. Assuming Gaussian initial conditions, we obtain galaxy biasing parameters $1/b_1=1.20^{+0.18}_{-0.19}$ and $b_2/b_1^2=-0.42\pm0.19$, with no sign of scale-dependent bias for $k\leq 0.3$ h/Mpc. These results impose stringent constraints on non-Gaussian initial conditions. For dimensional scaling models with $\chi^2_N$ statistics, we find N>49, which implies a constraint on primordial skewness $B_3<0.35$.Comment: 4 pages, 3 embedded figures, uses revtex style file, minor changes to reflect published versio

Multiple zero modes of the Dirac operator in three dimensions

One of the key properties of Dirac operators is the possibility of a degeneracy of zero modes. For the Abelian Dirac operator in three dimensions the construction of multiple zero modes has been sucessfully carried out only very recently. Here we generalise these results by discussing a much wider class of Dirac operators together with their zero modes. Further we show that those Dirac operators that do admit zero modes may be related to Hopf maps, where the Hopf index is related to the number of zero modes in a simple way.Comment: Latex file, 20 pages, no figure

Fermionic Determinant of the Massive Schwinger Model

A representation for the fermionic determinant of the massive Schwinger model, or $QED_2$, is obtained that makes a clean separation between the Schwinger model and its massive counterpart. From this it is shown that the index theorem for $QED_2$ follows from gauge invariance, that the Schwinger model's contribution to the determinant is canceled in the weak field limit, and that the determinant vanishes when the field strength is sufficiently strong to form a zero-energy bound state

Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy

Protecting the Primordial Baryon Asymmetry From Erasure by Sphalerons

If the baryon asymmetry of the universe was created at the GUT scale, sphalerons together with exotic sources of $(B-L)$-violation could have erased it, unless the latter satisfy stringent bounds. We elaborate on how the small Yukawa coupling of the electron drastically weakens previous estimates of these bounds.Comment: 41 pp., 4 latex figures included and 3 uuencoded or postscript figures available by request, UMN-TH-1213-9

Hyperextended Cosmological Perturbation Theory: Predicting Non-linear Clustering Amplitudes

We consider the long-standing problem of predicting the hierarchical clustering amplitudes $S_p$ in the strongly non-linear regime of gravitational evolution. N-body results for the non-linear evolution of the bispectrum (the Fourier transform of the three-point density correlation function) suggest a physically motivated ansatz that yields the strongly non-linear behavior of the skewness, $S_3$, starting from leading-order perturbation theory. When generalized to higher-order ($p>3$) polyspectra or correlation functions, this ansatz leads to a good description of non-linear amplitudes in the strongly non-linear regime for both scale-free and cold dark matter models. Furthermore, these results allow us to provide a general fitting formula for the non-linear evolution of the bispectrum that interpolates between the weakly and strongly non-linear regimes, analogous to previous expressions for the power spectrum.Comment: 20 pages, 6 figures. Final version accepted by ApJ. Includes new paragraphs on factorizable hierarchical models and agreement of HEPT with the excursion set model for white-noise Gaussian fluctuation

Instantons and the Ground State of the Massive Schwinger Model

We study the massive Schwinger model, quantum electrodynamics of massive, Dirac fermions, in 1+1 dimensions; with space compactified to a circle. In the limit that transitions to fermion--anti-fermion pairs can be neglected, we study the full ground state. We focus on the effect of instantons which mediate tunnelling transitions in the induced potential for the dynamical degree of freedom in the gauge field.Comment: 17 pages, plain te

A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications

The components of many signaling pathways have been identified and there is now a need to conduct quantitative data-rich temporal experiments for systems biology and modeling approaches to better understand pathway dynamics and regulation. Here we present a modified Western blotting method that allows the rapid and reproducible quantification and analysis of hundreds of data points per day on proteins and their phosphorylation state at individual sites. The approach is of particular use where samples show a high degree of sample-to-sample variability such as primary cells from multiple donors. We present a case study on the analysis of >800 phosphorylation data points from three phosphorylation sites in three signaling proteins over multiple time points from platelets isolated from ten donors, demonstrating the technique's potential to determine kinetic and regulatory information from limited cell numbers and to investigate signaling variation within a population. We envisage the approach being of use in the analysis of many cellular processes such as signaling pathway dynamics to identify regulatory feedback loops and the investigation of potential drug/inhibitor responses, using primary cells and tissues, to generate information about how a cell's physiological state changes over time

Characterisation of nerve‐mediated ATP release from bladder detrusor muscle and its pathological implications

Background and Purpose. To characterise the molecular mechanisms that determine variability of atropine‐resistance of nerve‐mediated contractions in human and guinea‐pig detrusor smooth muscle Experimental Approach. Atropine‐resistance of nerve‐mediated contractions, and the role of P2X1 receptors, was measured in isolated preparations from guinea‐pigs and also humans with or without overactive bladder syndrome, from which the mucosa was removed. Nerve‐mediated ATP release was measured directly with amperometric ATP‐sensitive electrodes. Ecto‐ATPase activity of guinea‐pig and human detrusor samples was measured in vitro by measuring the concentration‐dependent rate of ATP breakdown. The transcription of ecto‐ATPase subtypes in human samples was measured by qPCR. Key Results Atropine resistance was greatest in guinea‐pig detrusor, absent in human tissue from normally‐functioning bladders and intermediate in human overactive bladder. Greater atropine resistance correlated with reduction of contractions by the ATP‐diphospho‐hydrolase apyrase, directly implicating ATP in their generation. E‐NTPDase‐1 was the most abundantly transcribed ecto‐ATPase of those tested and transcription was reduced in tissue from human overactive, compared to normal, bladders. E‐NTPDase‐1 enzymatic activity was inversely related to the magnitude of atropine resistance. Nerve‐mediated ATP release was continually measured and varied with stimulation frequency over the range 1‐16 Hz. Conclusion and Implications Atropine‐resistance in nerve‐mediated detrusor contractions is due to ATP release and its magnitude is inversely related to E‐NTPDase‐1 activity. ATP is released under different stimulation conditions compared to acetylcholine that implies different routes for their release</p