Modular categories as representations of the 3-dimensional bordism 2-category

We show that once-extended anomalous 3-dimensional topological quantum field theories valued in the 2-category of k-linear categories are in canonical bijection with modular tensor categories equipped with a square root of the global dimension in each factor.Comment: 71 page

Two novel quantitative trait linkage analysis statistics based on the posterior probability of linkage: application to the COGA families

BACKGROUND: In this paper we apply two novel quantitative trait linkage statistics based on the posterior probability of linkage (PPL) to chromosome 4 from the GAW 14 COGA dataset. Our approaches are advantageous since they use the full likelihood, use full phenotypic information, do not assume normality at the population level or require population/sample parameter estimates; and like other forms of the PPL, they are specifically tailored to accumulate linkage evidence, either for or against linkage, across multiple sets of heterogeneous data. RESULTS: The first statistic uses all quantitative trait (QT) information from the pedigree (QT-posterior probability of linkage, PPL); we applied the QT-PPL to the trait ecb21 (resting electroencephalogram). The second statistic allows simultaneous incorporation of dichotomous trait data into the QT analysis via a threshold model (QTT-PPL); we applied the QTT-PPL to combined data on ecb21 and ALDX1. We obtained a QT-PPL of 96% at GABRB1 and a QT-PPL of 18% at FABP2 while the QTT-PPL was 4% and 2% at the same two loci, respectively. By comparison, the variance-components (VC) method, as implemented in SOLAR, yielded multipoint VC LOD scores of 2.05 and 2.21 at GABRB1 and FABP2, respectively; no other VC LODs were greater than 2. CONCLUSION: The QTT-PPL was only 4% at GABARB1, which might suggest that the underlying ecb21 gene does not also cause ALDX1, although features of the data complicate interpretation of this result

Extended 3-dimensional bordism as the theory of modular objects

A modular object in a symmetric monoidal bicategory is a Frobenius algebra object whose product and coproduct are biadjoint, equipped with a braided structure and a compatible twist, satisfying rigidity, ribbon, pivotality, and modularity conditions. We prove that the oriented 3-dimensional bordism bicategory of 1-, 2-, and 3-manifolds is the free symmetric monoidal bicategory on a single anomaly-free modular object.Comment: 64 page

Precise Re–Os ages of organic-rich mudrocks and the Os isotope composition of Jurassic seawater

Rhenium and osmium isotope and abundance data have been obtained on precisely-located samples from three suites of immature, organic-rich mudrocks from Jurassic coastal outcrops in England, The data provide accurate whole-rode ages of 207 +/- 12 Ma, 181 +/- 13 Ma and 155 +/- 4.3 Ma for suites of Hettangian, Toarcian (exaratum Subzone) and Kimmeridgian (sensu anglico, wheatleyensis Subzone) samples. These new Re-Os ages are indistinguishable, within the assigned analytical uncertainties, from interpolated depositional ages estimated from published geological timescales, and establish the importance of the Re-Os dating technique for chronostratigraphic studies. Early-diagenetic pyrite nodules possess levels of Re and Os which are similar to 1-2 orders of magnitude lower than in the enclosing organic-rich mudrocks, indicating that these elements had already been removed from sediment pore waters at the time of nodule formation. Thus the Re-Os isotope system in these organic-rich mudrocks has been closed since, or from very soon after, the time of sediment deposition. Because most of the Re (98+%) and Os (95-99.8+%) in the mudrocks is shown to be hydrogenous, the Os-187/Os-188((i)) of the samples is interpreted to be that of contemporaneous seawater. The data thereby provide the first estimates of the Os isotope composition of Jurassic seawater. During the earliest Jurassic (Hettangian), the seawater Os-187/Os-188 ratio was extremely unradiogenic (similar to 0.15); it had increased to similar to 0.8 at the end of the Early Jurassic (Toarcian) similar to 20 Ma later, while in the Late Jurassic (Kimmeridgian) the seawater Os-187/Os-188 ratio was similar to 0.59. The most likely explanation for the unradiogenic Os isotope composition of Hettangian seawater is that the contribution of unradiogenic Os to the oceans from the hydrothermal alteration of oceanic crust greatly exceeded the input of radiogenic Os from the continents at that time. This interpretation is in Line with observations suggesting that global weathering rates were low in the Hettangian, and that increased hydrothermal and volcanic activity preceded the break-up of Pangea. The Re/Os ratios of Hettangian mudrocks (and by inference, of contemporaneous seawater) are similar to those of mudrocks deposited at later times during the Jurassic, and argues against the unradiogenic Os in Hettangian seawater being derived from extraterrestrial meteoritic sources

De novo protein design:How do we expand into the universe of possible protein structures?

Protein scientists are paving the way to a new phase in protein design and engineering. Approaches and methods are being developed that could allow the design of proteins beyond the confines of natural protein structures. This possibility of designing entirely new proteins opens new questions: What do we build? How do we build into protein-structure space where there are few, if any, natural structures to guide us? To what uses can the resulting proteins be put? And, what, if anything, does this pursuit tell us about how natural proteins fold, function and evolve? We describe the origins of this emerging area of fully de novo protein design, how it could be developed, where it might lead, and what challenges lie ahead

Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial?

INTRODUCTION: Predictive cancer biomarkers to guide the right treatment to the right patient at the right time are strongly needed. The purpose of the present study was to validate prior results that tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or in combination with either HER2 or TOP2A copy number can be used to predict benefit from epirubicin (E) containing chemotherapy compared with cyclophosphamide, methotrexate and fluorouracil (CMF) treatment. METHODS: For the purpose of this study, formalin fixed paraffin embedded tumor tissue from women recruited into the BR9601 clinical trial, which randomized patients to E-CMF versus CMF, were analyzed for TIMP-1 immunoreactivity. Using previously collected data for HER2 amplification and TOP2A gene aberrations, we defined patients as "anthracycline non-responsive", that is, 2T (TIMP-1 immunoreactive and TOP2A normal) and HT (TIMP-1 immunoreactive and HER2 negative) and anthracycline responsive (all other cases). RESULTS: In total, 288 tumors were available for TIMP-1 analysis with (183/274) 66.8%, and (181/274) 66.0% being classed as 2T and HT responsive, respectively. TIMP-1 was neither associated with patient prognosis (relapse free survival or overall survival) nor with a differential effect of E-CMF and CMF. Also, TIMP-1 did not add to the predictive value of HER2, TOP2A gene aberrations, or to Ki67 immunoreactivity. CONCLUSION: This study could not confirm the predictive value of TIMP-1 immunoreactivity in patients randomized to receive E-CMF versus CMF as adjuvant treatment for primary breast cancer

BRG1 mutations found in human cancer cell lines inactivate Rb-mediated cell-cycle arrest

Eukaryotic organisms package DNA into chromatin for compact storage in the cell nucleus. However, this process promotes transcriptional repression of genes. To overcome the transcriptional repression, chromatin remodeling complexes have evolved that alter the configuration of chromatin packaging of DNA into nucleosomes by histones. The SWI/SNF chromatin remodeling complex uses energy from ATP hydrolysis to reposition nucleosomes and make DNA accessible to transcription factors. Recent studies showing mutations of BRG1, one of 2 mutually exclusive ATPase subunits, in human tumor cell lines and primary tissue samples have implicated a role for its loss in cancer development. While most of the mutations lead to complete loss of BRG1 protein expression, others result in single amino acid substitutions. To better understand the role of these BRG1 point mutations in cancer development, we characterized SWI/SNF function in human tumor cell lines with these mutations in the absence of BRM expression, the other ATPase component. We found that the mutant BRG1 proteins still interacted with the core complex members and appeared at the promoters of target genes. However, while these mutations did not affect CD44 and CDH1 expression, known targets of the SWI/SNF complex, they did abrogate Rb mediated cell cycle arrest. Therefore, our results implicate that these mutations disrupt the de novo chromatin remodeling activity of the complex without affecting the status of existing nucleosome positioning

Addressing the unmet need for visualizing Conditional Random Fields in Biological Data

Background: The biological world is replete with phenomena that appear to be ideally modeled and analyzed by one archetypal statistical framework - the Graphical Probabilistic Model (GPM). The structure of GPMs is a uniquely good match for biological problems that range from aligning sequences to modeling the genome-to-phenome relationship. The fundamental questions that GPMs address involve making decisions based on a complex web of interacting factors. Unfortunately, while GPMs ideally fit many questions in biology, they are not an easy solution to apply. Building a GPM is not a simple task for an end user. Moreover, applying GPMs is also impeded by the insidious fact that the complex web of interacting factors inherent to a problem might be easy to define and also intractable to compute upon. Discussion: We propose that the visualization sciences can contribute to many domains of the bio-sciences, by developing tools to address archetypal representation and user interaction issues in GPMs, and in particular a variety of GPM called a Conditional Random Field(CRF). CRFs bring additional power, and additional complexity, because the CRF dependency network can be conditioned on the query data. Conclusions: In this manuscript we examine the shared features of several biological problems that are amenable to modeling with CRFs, highlight the challenges that existing visualization and visual analytics paradigms induce for these data, and document an experimental solution called StickWRLD which, while leaving room for improvement, has been successfully applied in several biological research projects.Comment: BioVis 2014 conferenc