Stable directions for small nonlinear Dirac standing waves

We prove that for a Dirac operator with no resonance at thresholds nor eigenvalue at thresholds the propagator satisfies propagation and dispersive estimates. When this linear operator has only two simple eigenvalues close enough, we study an associated class of nonlinear Dirac equations which have stationary solutions. As an application of our decay estimates, we show that these solutions have stable directions which are tangent to the subspaces associated with the continuous spectrum of the Dirac operator. This result is the analogue, in the Dirac case, of a theorem by Tsai and Yau about the Schr\"{o}dinger equation. To our knowledge, the present work is the first mathematical study of the stability problem for a nonlinear Dirac equation.Comment: 62 page

Hard diffractive quarkonium hadroproduction at high energies

We present a study of heavy quarkonium production in hard diffractive process by the Pomeron exchange for Tevatron and LHC energies. The numerical results are computed using recent experimental determination of the diffractive parton density functions in Pomeron and are corrected by unitarity corrections through gap survival probability factor. We give predictions for single as well as central diffractive ratios. These processes are sensitive to the gluon content of the Pomeron at small Bjorken-x and may be particularly useful in studying the small-x physics. They may also be a good place to test the different available mechanisms for quarkonium production at hadron colliders.Comment: 7 pages, 3 figures, 1 table. Final version to be published in European Physical Journal

Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

Governance of microfinance institutions (MFIs) in Cameroon: What lessons can we learn?

The aim of this paper is to find out the effects of the COBAC regulations regulating the microfinance industry on the governance of microfinance institutions (MFIs) in Cameroon. The paper is based on 35 in-depth interviews carried out from May to June 2011 and June to July 2012 with managers and accountants from MFIs in Cameroon, MFI clients and non-clients, regulatory authorities in the Ministry of Finance, and accounting professionals. The findings show that the regulations have broken down the governance within the MFIs in Cameroon thus turning MFIs into hybrid organizations with managers striving to meet their shareholders' interests

Disorder-assisted error correction in Majorana chains

It was recently realized that quenched disorder may enhance the reliability of topological qubits by reducing the mobility of anyons at zero temperature. Here we compute storage times with and without disorder for quantum chains with unpaired Majorana fermions - the simplest toy model of a quantum memory. Disorder takes the form of a random site-dependent chemical potential. The corresponding one-particle problem is a one-dimensional Anderson model with disorder in the hopping amplitudes. We focus on the zero-temperature storage of a qubit encoded in the ground state of the Majorana chain. Storage and retrieval are modeled by a unitary evolution under the memory Hamiltonian with an unknown weak perturbation followed by an error-correction step. Assuming dynamical localization of the one-particle problem, we show that the storage time grows exponentially with the system size. We give supporting evidence for the required localization property by estimating Lyapunov exponents of the one-particle eigenfunctions. We also simulate the storage process for chains with a few hundred sites. Our numerical results indicate that in the absence of disorder, the storage time grows only as a logarithm of the system size. We provide numerical evidence for the beneficial effect of disorder on storage times and show that suitably chosen pseudorandom potentials can outperform random ones.Comment: 50 pages, 7 figure

Non-canonical HIF-1 stabilization contributes to intestinal tumorigenesis

The hypoxia-inducible transcription factor HIF-1 is appreciated as a promising target for cancer therapy. However, conditional deletion of HIF-1 and HIF-1 target genes in cells of the tumor microenvironment can result in accelerated tumor growth, calling for a detailed characterization of the cellular context to fully comprehend HIF-1's role in tumorigenesis. We dissected cell type-specific functions of HIF-1 for intestinal tumorigenesis by lineage-restricted deletion of the Hif1a locus. Intestinal epithelial cell-specific Hif1a loss reduced activation of Wnt/β-catenin, tumor-specific metabolism and inflammation, significantly inhibiting tumor growth. Deletion of Hif1a in myeloid cells reduced the expression of fibroblast-activating factors in tumor-associated macrophages resulting in decreased abundance of tumor-associated fibroblasts (TAF) and robustly reduced tumor formation. Interestingly, hypoxia was detectable only sparsely and without spatial association with HIF-1α, arguing for an importance of hypoxia-independent, i.e., non-canonical, HIF-1 stabilization for intestinal tumorigenesis that has not been previously appreciated. This adds a further layer of complexity to the regulation of HIF-1 and suggests that hypoxia and HIF-1α stabilization can be uncoupled in cancer. Collectively, our data show that HIF-1 is a pivotal pro-tumorigenic factor for intestinal tumor formation, controlling key oncogenic programs in both the epithelial tumor compartment and the tumor microenvironment

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the