Vanishing of Quartic and Sextic Twists of LL-functions

Let $E$ be an elliptic curve over $\mathbf{Q}$. We conjecture asymptotic estimates for the number of vanishings of $L(E,1,\chi)$ as $\chi$ varies over all primitive Dirichlet characters of orders 4 and 6, subject to a mild hypothesis on $E$. Our conjectures about these families come from conjectures about random unitary matrices as predicted by the philosophy of Katz-Sarnak. We support our conjectures with numerical evidence. Earlier work by David, Fearnley and Kisilevsky formulates analogous conjectures for characters of any odd prime order. In the composite order case, however, we need to justify our use of random matrix theory heuristics by analyzing the equidistribution of the squares of normalized Gauss sums. Along the way we introduce the notion of totally order $\ell$ characters to quantify how quickly quartic and sextic Gauss sums become equidistributed. Surprisingly, the rate of equidistribution in the full family of quartic (sextic, resp.) characters is much slower than in the sub-family of totally quartic (sextic, resp.) characters. A conceptual explanation for this phenomenon is that the full family of order $\ell$ twisted elliptic curve $L$-functions, with $\ell$ even and composite, is a mixed family with both unitary and orthogonal aspects.Comment: 31 pages, 5 figure

Uncoupling cancer mutations reveals critical timing of p53 loss in sarcomagenesis

It is well accepted that cancer develops following the sequential accumulation of multiple alterations, but how the temporal order of events affects tumor initiation and/or progression remains largely unknown. Here, we describe a mouse model that allows for temporally distinct cancer mutations. By integrating a Flp-inducible allele of K-ras[superscript G12D] with established methods for Cre-mediated p53 deletion, we were able to separately control the mutation of these commonly associated cancer genes in vitro and in vivo. We show that delaying p53 deletion relative to K-ras[superscript G12D] activation reduced tumor burden in a mouse model of soft-tissue sarcoma, suggesting that p53 strongly inhibits very early steps of transformation in the muscle. Furthermore, using in vivo RNA interference, we implicate the p53 target gene p21 as a critical mediator in this process, highlighting cell-cycle arrest as an extremely potent tumor suppressor mechanism.National Institutes of Health (U.S.) (grant 5-U01-CA84306)National Cancer Institute (U.S.) (Cancer Center Support (core) Grant P30-CA14051)Howard Hughes Medical Institute (Investigator)Virginia and D.K. Ludwig Fund for Cancer Research (Scholar

What is the most efficient and effective method for long-term monitoring of alpine tundra vegetation?

Nondestructive estimations of plant community characteristics are essential to vegetation monitoring programs. However, there is no universally accepted method for this purpose in the Arctic, partly because not all programs share the same logistical constraints and monitoring goals. Our aim was to determine the most efficient and effective method for long-term monitoring of alpine tundra vegetation. To achieve this, we established 12 vegetation-monitoring plots on a south-facing slope in the alpine tundra of southern Yukon Territory, Canada. Four observers assessed these plots for vascular plant species abundance employing three methods: visual cover (VC) and subplot frequency (SF) estimation and modified point-intercept (PI) (includes rare species present but not intersected by a pin). SF performed best in terms of time required per plot and sensitivity to variations in species richness. All methods were similarly poor at estimating relative abundance for rare species, but PI and VC were substantially better at high abundances. Differences among methods were larger than among observers. Our results suggest that SF is best when the monitoring focus is on rare species or species richness across extensive areas. However, when the focus is on monitoring changes in relative abundance of common species, VC or PI should be preferred

Broadband UBVRI Photometry of Horizontal-Branch and Metal-Poor Candidates from the HK and Hamburg/ESO Surveys. I

We report broadband UBV and/or BVRI CCD photometry for a total of 1857 stars in the thick-disk and halo populations of the Galaxy. The majority of our targets were selected as candidate field horizontal-branch or other A-type stars (FHB/A, N = 576), or candidate low-metallicity stars (N = 1221), from the HK and Hamburg/ESO objective-prism surveys. Similar data for a small number of additional stars from other samples are also reported. These data are being used for several purposes. In the case of the FHB/A candidates they are used to accurately separate the lower-gravity FHB stars from various higher-gravity A-type stars, a subsample that includes the so-called Blue Metal Poor stars, halo and thick-disk blue stragglers, main-sequence A-type dwarfs, and Am and Ap stars. These data are also being used to derive photometric distance estimates to high-velocity hydrogen clouds in the Galaxy and for improved measurements of the mass of the Galaxy. Photometric data for the metal-poor candidates are being used to refine estimates of stellar metallicity for objects with available medium-resolution spectroscopy, to obtain distance estimates for kinematic analyses, and to establish initial estimates of effective temperature for analysis of high-resolution spectroscopy of the stars for which this information now exists.Comment: 22 pages, including 3 figures, 5 tables, and two ascii files of full data, accepted for publication in the Astrophysical Journal (Supplements

Broadband UBVR_CI_C Photometry of Horizontal-Branch and Metal-poor Candidates from the HK and Hamburg/ESO Surveys. I.

We report broadband UBV and/or BVR_CI_C CCD photometry for a total of 1857 stars in the thick-disk and halo populations of the Galaxy. The majority of our targets were selected as candidate field horizontal-branch or other A-type stars (FHB/A, N = 576), or candidate low-metallicity stars (N = 1221), from the HK and Hamburg/ESO objective-prism surveys. Similar data for a small number of additional stars from other samples are also reported. These data are being used for several purposes. In the case of the FHB/A candidates they are used to accurately separate the lower gravity FHB stars from various higher gravity A-type stars, a subsample that includes the so-called blue metal poor stars, halo and thick-disk blue stragglers, main-sequence A-type dwarfs, and Am and Ap stars. These data are also being used to derive photometric distance estimates to high-velocity hydrogen clouds in the Galaxy and for improved measurements of the mass of the Galaxy. Photometric data for the metal-poor candidates are being used to refine estimates of stellar metallicity for objects with available medium-resolution spectroscopy, to obtain distance estimates for kinematic analyses, and to establish initial estimates of effective temperature for analysis of high-resolution spectroscopy of the stars for which this information now exists

AMP-activated protein kinase mediates mitochondrial fission in response to energy stress

Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA–linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)–activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Numerical models of collisions between core-collapse supernovae and circumstellar shells

Recent observations of luminous Type IIn supernovae (SNe) provide compelling evidence that massive circumstellar shells surround their progenitors. In this paper we investigate how the properties of such shells influence the SN lightcurve by conducting numerical simulations of the interaction between an expanding SN and a circumstellar shell ejected a few years prior to core collapse. Our parameter study explores how the emergent luminosity depends on a range of circumstellar shell masses, velocities, geometries, and wind mass-loss rates, as well as variations in the SN mass and energy. We find that the shell mass is the most important parameter, in the sense that higher shell masses (or higher ratios of M_shell/M_SN) lead to higher peak luminosities and higher efficiencies in converting shock energy into visual light. Lower mass shells can also cause high peak luminosities if the shell is slow or if the SN ejecta are very fast, but only for a short time. Sustaining a high luminosity for durations of more than 100 days requires massive circumstellar shells of order 10 M_sun or more. This reaffirms previous comparisons between pre-SN shells and shells produced by giant eruptions of luminous blue variables (LBVs), although the physical mechanism responsible for these outbursts remains uncertain. The lightcurve shape and observed shell velocity can help diagnose the approximate size and density of the circumstellar shell, and it may be possible to distinguish between spherical and bipolar shells with multi-wavelength lightcurves. These models are merely illustrative. One can, of course, achieve even higher luminosities and longer duration light curves from interaction by increasing the explosion energy and shell mass beyond values adopted here.Comment: Accepted for publication in MNRAS. Tables of numerical results (SN lightcurves and velocities) to be published online. (Updated to fix figures