Numerical Hermitian Yang-Mills Connections and Vector Bundle Stability in Heterotic Theories

A numerical algorithm is presented for explicitly computing the gauge connection on slope-stable holomorphic vector bundles on Calabi-Yau manifolds. To illustrate this algorithm, we calculate the connections on stable monad bundles defined on the K3 twofold and Quintic threefold. An error measure is introduced to determine how closely our algorithmic connection approximates a solution to the Hermitian Yang-Mills equations. We then extend our results by investigating the behavior of non slope-stable bundles. In a variety of examples, it is shown that the failure of these bundles to satisfy the Hermitian Yang-Mills equations, including field-strength singularities, can be accurately reproduced numerically. These results make it possible to numerically determine whether or not a vector bundle is slope-stable, thus providing an important new tool in the exploration of heterotic vacua.Comment: 52 pages, 15 figures. LaTex formatting of figures corrected in version 2

Higgs Multiplets in Heterotic GUT Models

For supersymmetric GUT models from heterotic string theory, built from a stable holomorphic SU(n) vector bundle $V$ on a Calabi-Yau threefold $X$, the net amount of chiral matter can be computed by a Chern class computation. Corresponding computations for the number $N_H$ of Higgses lead for the phenomenologically relevant cases of GUT group SU(5) or SO(10) to consideration of the bundle \La^2 V. In a class of bundles where everything can be computed explicitly (spectral bundles on elliptic $X$) we find that the computation for $N_H$ gives a result which is in conflict with expectations. We argue that this discrepancy has its origin in the subtle geometry of the spectral data for \La^2 V and that taking this subtlety into account properly should resolve the problem.Comment: 29 pages; comments and references adde

Moduli restriction and Chiral Matter in Heterotic String Compactifications

Supersymmetric heterotic string models, built from a stable holomorphic vector bundle $V$ on a Calabi-Yau threefold $X$, usually come with many vector bundle moduli whose stabilisation is a difficult and complex task. It is therefore of interest to look for bundle constructions which, from the outset, have as few as possible bundle moduli. One way to reach such a set-up is to start from a generic construction and to make discrete modifications of it which are available only over a subset of the bundle moduli space. Turning on such discrete 'twists' constrains the moduli to the corresponding subset of their moduli space: the twisted bundle has less parametric freedom. We give an example of a set-up where this idea can be considered concretely. Such non-generic twists lead also to new contributions of chiral matter (which greatly enhances the flexibility in model building); their computation constitutes the main issue of this note.Comment: 37 pages; comments and references adde

Supersymmetric Hidden Sectors for Heterotic Standard Models

Within the context of the weakly coupled E 8 × E 8 heterotic string, we study the hidden sector of heterotic standard model compactifications to four-dimensions. Specifically, we present a class of hidden sector vector bundles — composed of the direct sum of line bundles only — that, together with an effective bulk five-brane, renders the heterotic standard model entirely N = 1 supersymmetric. Two explicit hidden sectors are constructed and analyzed in this context; one with the gauge group E 7 × U(1) arising from a single line bundle and a second with an SO(12) × U(1) × U(1) gauge group constructed from the direct sum of two line bundles. Each hidden sector bundle is shown to satisfy all requisite physical constraints within a finite region of the Kähler cone. We also clarify that the first Chern class of the line bundles need not be even in our context, as has often been imposed in the model building literature

Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave, China

The association between solar activity and Asian monsoon (AM) remains unclear. Here we evaluate the possible connection between them based on a precisely-dated, high-resolution speleothem oxygen isotope record from Dongge Cave, southwest China during the past 4.2 thousand years (ka). Without being adjusted chronologically to the solar signal, our record shows a distinct peak-to-peak correlation with cosmogenic nuclide 14C, total solar irradiance (TSI) and sunspot number (SN) at multi-decadal to centennial timescales. Further cross-wavelet analyses between our calcite δ18O and atmospheric 14C show statistically strong coherence at three typical periodicities of ~80, 200 and 340 years, suggesting important roles of solar activities in modulating AM changes at those timescales. Our result has further indicated a better correlation between our calcite δ18O record and atmospheric 14C than between our record and TSI. This better correlation may imply that the Sun–monsoon connection is dominated most likely by cosmic rays and oceanic circulation (both associated to atmospheric 14C), instead of the direct solar heating (TSI)

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

Human Tumor Cell Proliferation Evaluated Using Manganese-Enhanced MRI

Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+) [measured with manganese-enhanced MRI (MEMRI)], is linked to proliferation rate in vitro.Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2) for one hour and then thoroughly washed. MEMRI R(1) values (longitudinal relaxation rates), which have a positive linear relationship with Mn(2+) concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+)-induced increases in R(1) compared to cells not exposed to Mn(2+). C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1) values and proliferation rate (p≤0.005), while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1) for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet.These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI