Refined saddle-point preconditioners for discretized Stokes problems

This paper is concerned with the implementation of efficient solution algorithms for elliptic problems with constraints. We establish theory which shows that including a simple scaling within well-established block diagonal preconditioners for Stokes problems can result in significantly faster convergence when applying the preconditioned MINRES method. The codes used in the numerical studies are available online

Shot Noise through a Quantum Dot in the Kondo Regime

The shot noise in the current through a quantum dot is calculated as a function of voltage from the high-voltage, Coulomb blockaded regime to the low-voltage, Kondo regime. Using several complementary approaches, it is shown that the zero-frequency shot noise (scaled by the voltage) exhibits a non-monotonic dependence on voltage, with a peak around the Kondo temperature. Beyond giving a good estimate of the Kondo temperature, it is shown that the shot noise yields additional information on the effects of electronic correlations on the local density of states in the Kondo regime, unaccessible in traditional transport measurements.Comment: 4 pages, 1 figur

Bihelical Magnetic Relaxation and Large Scale Magnetic Field Growth

A unified, three-scale system of equations accommodating nonlinear velocity driven helical dynamos, as well as time-dependent relaxation of magnetically dominated unihelical or bihelical systems is derived and solved herein. When opposite magnetic helicities of equal magnitude are injected on the intermediate and small scales, the large scale magnetic helicity grows kinematically (independent of the magnetic Reynolds number) to equal that on the intermediate scale. For both free and driven relaxation large scale fields are rapidly produced. Subsequently, a dissipation-limited dynamo, driven by growth of small scale kinetic helicity, further amplifies the large scale field. The results are important for astrophysical coronae fed with bihelical structures by dynamos in their host rotators. The large scale for the rotator corresponds to the intermediate scale for the corona. That bihelical magnetic relaxation can produce global scale fields may help to explain the formation of astrophysical coronal holes and magnetohydrodynamic outflows.Comment: LaTeX, 29 pages including figures, version in press, Physics of Plasma

Quantum Dot in the Kondo Regime coupled to p-wave superconductors

This paper studies the physics of junctions containing superconducting $(S)$ and normal $(N)$ leads weakly coupled to an Anderson impurity in the Kondo regime $(K)$. Special attention is devoted to the case where one of the leads is a $p-wave$ superconductor where mid-gap surface states play an important role in the tunneling processes and help the formation of Kondo resonance. The novel physics in these systems beyond that encountered in quantum dots coupled only to to normal leads is that electron transport at finite bias $eV$ in $SKN$ and $SKS$ junctions is governed by Andreev reflections. These enable the occurrence of dissipative current even when the bias $eV$ is smaller than the superconducting gap $\Delta$. Using the slave boson mean field approximation the current, shot-noise power and Fano factor are calculated as functions of the applied bias voltage in the sub-gap region $eV < \Delta$ and found to be strongly dependent on the ratio $t_K$ between the Kondo temperature $T_{K}$ and the superconducting gap $\Delta$. In particular, for large values of $t_K$ the attenuation of current due to the existence of the superconducting gap is compensated by the Kondo effect. This scenario is manifested also in the behavior of the Josephson current as function of temperature.Comment: 7 pages, 5 .eps figure

Identifying Causal Genes and Dysregulated Pathways in Complex Diseases

In complex diseases, various combinations of genomic perturbations often lead to the same phenotype. On a molecular level, combinations of genomic perturbations are assumed to dys-regulate the same cellular pathways. Such a pathway-centric perspective is fundamental to understanding the mechanisms of complex diseases and the identification of potential drug targets. In order to provide an integrated perspective on complex disease mechanisms, we developed a novel computational method to simultaneously identify causal genes and dys-regulated pathways. First, we identified a representative set of genes that are differentially expressed in cancer compared to non-tumor control cases. Assuming that disease-associated gene expression changes are caused by genomic alterations, we determined potential paths from such genomic causes to target genes through a network of molecular interactions. Applying our method to sets of genomic alterations and gene expression profiles of 158 Glioblastoma multiforme (GBM) patients we uncovered candidate causal genes and causal paths that are potentially responsible for the altered expression of disease genes. We discovered a set of putative causal genes that potentially play a role in the disease. Combining an expression Quantitative Trait Loci (eQTL) analysis with pathway information, our approach allowed us not only to identify potential causal genes but also to find intermediate nodes and pathways mediating the information flow between causal and target genes. Our results indicate that different genomic perturbations indeed dys-regulate the same functional pathways, supporting a pathway-centric perspective of cancer. While copy number alterations and gene expression data of glioblastoma patients provided opportunities to test our approach, our method can be applied to any disease system where genetic variations play a fundamental causal role

Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells

BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the Hoxa9 regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis-elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the Hoxa9 locus. CONCLUSION: These results suggest a functional link among Cdx4, menin and histone modifications in Hoxa9 regulation in hematopoietic cells

Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges

Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base–driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Changes to the Fossil Record of Insects through Fifteen Years of Discovery

The first and last occurrences of hexapod families in the fossil record are compiled from publications up to end-2009. The major features of these data are compared with those of previous datasets (1993 and 1994). About a third of families (>400) are new to the fossil record since 1994, over half of the earlier, existing families have experienced changes in their known stratigraphic range and only about ten percent have unchanged ranges. Despite these significant additions to knowledge, the broad pattern of described richness through time remains similar, with described richness increasing steadily through geological history and a shift in dominant taxa, from Palaeoptera and Polyneoptera to Paraneoptera and Holometabola, after the Palaeozoic. However, after detrending, described richness is not well correlated with the earlier datasets, indicating significant changes in shorter-term patterns. There is reduced Palaeozoic richness, peaking at a different time, and a less pronounced Permian decline. A pronounced Triassic peak and decline is shown, and the plateau from the mid Early Cretaceous to the end of the period remains, albeit at substantially higher richness compared to earlier datasets. Origination and extinction rates are broadly similar to before, with a broad decline in both through time but episodic peaks, including end-Permian turnover. Origination more consistently exceeds extinction compared to previous datasets and exceptions are mainly in the Palaeozoic. These changes suggest that some inferences about causal mechanisms in insect macroevolution are likely to differ as well