Nonequilibrium Transport through a Kondo Dot in a Magnetic Field: Perturbation Theory

Using nonequilibrium perturbation theory, we investigate the nonlinear transport through a quantum dot in the Kondo regime in the presence of a magnetic field. We calculate the leading logarithmic corrections to the local magnetization and the differential conductance, which are characteristic of the Kondo effect out of equilibrium. By solving a quantum Boltzmann equation, we determine the nonequilibrium magnetization on the dot and show that the application of both a finite bias voltage and a magnetic field induces a novel structure of logarithmic corrections not present in equilibrium. These corrections lead to more pronounced features in the conductance, and their form calls for a modification of the perturbative renormalization group.Comment: 16 pages, 7 figure

Basis Functions for Linear-Scaling First-Principles Calculations

In the framework of a recently reported linear-scaling method for density-functional-pseudopotential calculations, we investigate the use of localized basis functions for such work. We propose a basis set in which each local orbital is represented in terms of an array of `blip functions'' on the points of a grid. We analyze the relation between blip-function basis sets and the plane-wave basis used in standard pseudopotential methods, derive criteria for the approximate equivalence of the two, and describe practical tests of these criteria. Techniques are presented for using blip-function basis sets in linear-scaling calculations, and numerical tests of these techniques are reported for Si crystal using both local and non-local pseudopotentials. We find rapid convergence of the total energy to the values given by standard plane-wave calculations as the radius of the linear-scaling localized orbitals is increased.Comment: revtex file, with two encapsulated postscript figures, uses epsf.sty, submitted to Phys. Rev.

Non-linear response of a Kondo system: Perturbation approach to the time dependent Anderson impurity model

Nonlinear tunneling current through a quantum dot (an Anderson impurity system) subject to both constant and alternating electric fields is studied in the Kondo regime. A systematic diagram technique is developed for perturbation study of the current in physical systems out of equilibrium governed by time - dependent Hamiltonians of the Anderson and the Kondo models. The ensuing calculations prove to be too complicated for the Anderson model, and hence, a mapping on an effective Kondo problem is called for. This is achieved by constructing a time - dependent version of the Schrieffer - Wolff transformation. Perturbation expansion of the current is then carried out up to third order in the Kondo coupling J yielding a set of remarkably simple analytical expressions for the current. The zero - bias anomaly of the direct current differential conductance is shown to be suppressed by the alternating field while side peaks develop at finite source - drain voltage. Both the direct component and the first harmonics of the time - dependent response are equally enhanced due to the Kondo effect, while amplitudes of higher harmonics are shown to be relatively small. A zero alternating bias anomaly is found in the alternating current differential conductance, that is, it peaks around zero alternating bias. This peak is suppressed by the constant bias. No side peaks show up in the differential alternating - conductance but their counterpart is found in the derivative of the alternating current with respect to the direct bias. The results pertaining to nonlinear response are shown to be valid also below the Kondo temperature.Comment: 55 latex pages 11 ps figure

Towards a Linear-Scaling DFT Technique: The Density Matrix Approach

A recently proposed linear-scaling scheme for density-functional pseudopotential calculations is described in detail. The method is based on a formulation of density functional theory in which the ground state energy is determined by minimization with respect to the density matrix, subject to the condition that the eigenvalues of the latter lie in the range [0,1]. Linear-scaling behavior is achieved by requiring that the density matrix should vanish when the separation of its arguments exceeds a chosen cutoff. The limitation on the eigenvalue range is imposed by the method of Li, Nunes and Vanderbilt. The scheme is implemented by calculating all terms in the energy on a uniform real-space grid, and minimization is performed using the conjugate-gradient method. Tests on a 512-atom Si system show that the total energy converges rapidly as the range of the density matrix is increased. A discussion of the relation between the present method and other linear-scaling methods is given, and some problems that still require solution are indicated.Comment: REVTeX file, 27 pages with 4 uuencoded postscript figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics