Correlated time-dependent transport through a 2D quantum structure

We use a generalized master equation (GME) to describe the nonequilibrium magnetotransport of interacting electrons through a broad finite quantum wire with an embedded ring structure. The finite quantum wire is weakly coupled to two broad leads acting as reservoirs of electrons. The mutual Coulomb interaction of the electrons is described using a configuration interaction method for the many-electron states of the central system. We report some non-trivial interaction effects both at the level of time-dependent filling of states and on the time-dependent transport. We find that the Coulomb interaction in this non-trivial geometry can enhance the correlation of electronic states in the system and facilitate it's charging in certain circumstances in the weak coupling limit appropriate for the GME. In addition, we find oscillations in the current in the leads due to the correlations oscillations caused by the switched-on lead- system coupling. The oscillations are influenced and can be enhanced by the external magnetic field and the Coulomb interaction.Comment: RevTeX (pdf-LaTeX), 10 pages with 15 included jpg figure

Nonperturbative Approach to Circuit Quantum Electrodynamics

We outline a rigorous method which can be used to solve the many-body Schroedinger equation for a Coulomb interacting electronic system in an external classical magnetic field as well as a quantized electromagnetic field. Effects of the geometry of the electronic system as well as the polarization of the quantized electromagnetic field are explicitly taken into account. We accomplish this by performing repeated truncations of many-body spaces in order to keep the size of the many particle basis on a manageable level. The electron-electron and electron-photon interactions are treated in a nonperturbative manner using "exact numerical diagonalization". Our results demonstrate that including the diamagnetic term in the photon-electron interaction Hamiltonian drastically improves numerical convergence. Additionally, convergence with respect to the number of photon states in the joint photon-electron Fock space basis is fast. However, the convergence with respect to the number of electronic states is slow and is the main bottleneck in calculations.Comment: Revtex, pdflatex, 8 pages, with 5 included pdf figure

Time-dependent transport of electrons through a photon cavity

We use a non-Markovian master equation to describe the transport of Coulomb interacting electrons through an electromagnetic cavity with one quantized photon mode. The central system is a finite parabolic quantum wire that is coupled weakly to external parabolic quasi-one-dimensional leads at $t=0$. With a stepwise introduction of complexity to the description of the system and a corresponding stepwise truncation of the ensuing many-body spaces we are able to describe the time-dependent transport of Coulomb-interacting electrons through a geometrically complex central system. We take into account the full electromagnetic interaction of electrons and cavity photons without resorting to the rotating wave approximation or reduction of the electron states to two levels. We observe that the number of initial cavity photons and their polarization can have important effects on the transport properties of the system. The quasiparticles formed in the central system have a lifetime limited by the coupling to the leads and radiation processes active on a much longer timescale.Comment: RevTeX (pdf-LaTeX) 11 pages with 12 jpg-figures include

Symmetric excitation and de-excitation of a cavity QED system

We calculate the time evolution of a cavity-QED system subject to a time dependent sinusoidal drive. The drive is modulated by an envelope function with the shape of a pulse. The system consists of electrons embedded in a semiconductor nanostructure which is coupled to a single mode quantized electromagnetic field. The electron-electron as well as photon-electron interaction is treated exactly using "exact numerical diagonalization" and the time evolution is calculated by numerically solving the equation of motion for the system's density matrix. We find that the drive causes symmetric excitation and de-excitation where the system climbs up the Jaynes-Cummings ladder and descends back down symmetrically into its original state. This effect persists even in the ultra-strong coupling regime where the Jaynes-Cummings model is invalid. We investigate the robustness of this symmetric behavior with respect to the drive de-tuning and pulse duration

Quantum magneto-electrodynamics of electrons embedded in a photon cavity

We investigate the coupling between a quantized electromagnetic field in a cavity resonator and a Coulomb interacting electronic system in a nanostructure in an external magnetic field. Effects caused by the geometry of the electronic system and the polarization of the electromagnetic field are explicitly taken into account. Our numerical results demonstrate that the two-level system approximation and the Jaynes-Cummings model remain valid in the weak electron-photon coupling regime, while the quadratic vector potential in the diamagnetic part of the charge current leads to significant correction to the energy spectrum in the strong coupling regime. Furthermore, we find that a coupling to a strong cavity photon mode polarizes the charge distribution of the system requiring a large basis of single-electron eigenstates to be included in the model.Comment: LaTeX 16 pages with included 5 eps figure

Genomic profiling of breast tumours in relation to BRCA abnormalities and phenotypes

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldINTRODUCTION: Germline mutations in the BRCA1 and BRCA2 genes account for a considerable fraction of familial predisposition to breast cancer. Somatic mutations in BRCA1 and BRCA2 have not been found and the involvement of these genes in sporadic tumour development therefore remains unclear. METHODS: The study group consisted of 67 primary breast tumours with and without BRCA1 or BRCA2 abnormalities. Genomic alterations were profiled by high-resolution (~7 kbp) comparative genome hybridisation (CGH) microarrays. Tumour phenotypes were analysed by immunohistochemistry on tissue microarrays using selected biomarkers (ER, PR, HER-2, EGFR, CK5/6, CK8, CK18). RESULTS: Classification of genomic profiles through cluster analysis revealed four subgroups, three of which displayed high genomic instability indices (GII). Two of these GII-high subgroups were enriched with either BRCA1- or BRCA2-related tumours whereas the third was not BRCA-related. The BRCA1-related subgroup mostly displayed non-luminal phenotypes, of which basal-like were most prominent, whereas the other two genomic instability subgroups BRCA2- and GII-high-III (non-BRCA), were almost entirely of luminal phenotype. Analysis of genome architecture patterns revealed similarities between the BRCA1- and BRCA2 subgroups, with long deletions being prominent. This contrasts with the third instability subgroup, not BRCA-related, where small gains were more prominent. CONCLUSIONS: The results suggest that BRCA1- and BRCA2-related tumours develop largely through distinct genetic pathways in terms of the regions altered while also displaying distinct phenotypes. Importantly, we show that the development of a subset of sporadic tumours is similar to that of either familial BRCA1- or BRCA2 tumours. Despite their differences, we observed clear similarities between the BRCA1- and BRCA2-related subgroups reflected in the type of genomic alterations acquired with deletions of long DNA segments being prominent. This suggests similarities in the mechanisms promoting genomic instability for BRCA1- and BRCA2-associated tumours, possibly relating to deficiency in DNA repair through homologous recombination. Indeed, this feature characterized both familial and sporadic tumours displaying BRCA1- or BRCA2-like spectrums of genomic alterations. The importance of these findings lies in the potential benefit from targeted therapy, through the use of agents leading to DNA double-strand breaks such as PARP inhibitors (olaparib) and cisplatin, for a much larger group of patients than the few BRCA1 and BRCA2 germline mutation carriers

CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesDNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E. coli AlkB homologs ALKBH2 and ALKBH3 have also been linked to direct reversal of alkylation damage. However, it is currently unknown whether ALKBH2 or ALKBH3 are found inactivated in cancer.Methylome datasets (GSE52865, GSE20713, GSE69914), available through Omnibus, were used to determine whether ALKBH2 or ALKBH3 are found inactivated by CpG promoter methylation. TCGA dataset enabled us to then assess the impact of CpG promoter methylation on mRNA expression for both ALKBH2 and ALKBH3. DNA methylation analysis for the ALKBH3 promoter region was carried out by pyrosequencing (PyroMark Q24) in 265 primary breast tumours and 30 proximal normal breast tissue samples along with 8 breast-derived cell lines. ALKBH3 mRNA and protein expression were analysed in cell lines using RT-PCR and Western blotting, respectively. DNA alkylation damage assay was carried out in cell lines based on immunofluorescence and confocal imaging. Data on clinical parameters and survival outcomes in patients were obtained and assessed in relation to ALKBH3 promoter methylation.The ALKBH3 gene, but not ALKBH2, undergoes CpG promoter methylation and transcriptional silencing in breast cancer. We developed a quantitative alkylation DNA damage assay based on immunofluorescence and confocal imaging revealing higher levels of alkylation damage in association with epigenetic inactivation of the ALKBH3 gene (P = 0.029). In our cohort of 265 primary breast cancer, we found 72 cases showing aberrantly high CpG promoter methylation over the ALKBH3 promoter (27%; 72 out of 265). We further show that increasingly higher degree of ALKBH3 promoter methylation is associated with reduced breast-cancer specific survival times in patients. In this analysis, ALKBH3 promoter methylation at >20% CpG methylation was found to be statistically significantly associated with reduced survival (HR = 2.3; P = 0.012). By thresholding at the clinically relevant CpG methylation level (>20%), we find the incidence of ALKBH3 promoter methylation to be 5% (13 out of 265).ALKBH3 is a novel addition to the catalogue of DNA repair genes found inactivated in breast cancer. Our results underscore a link between defective alkylation repair and breast cancer which, additionally, is found in association with poor disease outcome.Icelandic Centre for Researc

Genomic and phenotypic analysis of BRCA2 mutated breast cancers reveals co-occurring changes linked to progression

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Inherited mutations in the BRCA2 gene greatly increase the risk of developing breast cancer. Consistent with an important role for BRCA2 in error-free DNA repair, complex genomic changes are frequently observed in tumors derived from BRCA2 mutation carriers. Here, we explore the impact of DNA copy-number changes in BRCA2 tumors with respect to phenotype and clinical staging of the disease. METHODS: Breast tumors (n = 33) derived from BRCA2 999del5 mutation carriers were examined in terms of copy-number changes with high-resolution aCGH (array comparative genomic hybridization) containing 385 thousand probes (about one for each 7 kbp) and expression of phenotypic markers on TMAs (tissue microarrays). The data were examined with respect to clinical parameters including TNM staging, histologic grade, S phase, and ploidy. RESULTS: Tumors from BRCA2 carriers of luminal and basal/triple-negative phenotypes (TNPs) differ with respect to patterns of DNA copy-number changes. The basal/TNP subtype was characterized by lack of pRb (RB1) coupled with high/intense expression of p16 (CDKN2A) gene products. We found increased proportions of Ki-67-positive cells to be significantly associated with loss of the wild-type (wt) BRCA2 allele in luminal types, whereas BRCA2wt loss was less frequent in BRCA2 tumors displaying basal/TNP phenotypes. Furthermore, we show that deletions at 13q13.1, involving the BRCA2wt allele, represents a part of a larger network of co-occurring genetic changes, including deletions at 6q22.32-q22.33, 11q14.2-q24.1, and gains at 17q24.1. Importantly, copy-number changes at these BRCA2-linked networking regions coincide with those associated with advanced progression, involving the capacity to metastasize to the nodes or more-distant sites at diagnosis. CONCLUSIONS: The results presented here demonstrate divergent paths of tumor evolution in BRCA2 carriers and that deletion of the wild-type BRCA2 allele, together with co-occurring changes at 6 q, 11 q, and 17 q, are important events in progression toward advanced disease.Eimskipafelag University Minningarsjodur Bergthoru Magnusdottur and Jakobs J Bjarnasonar Gongum Saman Icelandic Cancer Research Fund SKI Icelandic Centre for Research RANNIS The University of Icelan

CpG promoter hypo-methylation and up-regulation of microRNA-190b in hormone receptor-positive breast cancer

Publisher's version (útgefin grein)Estrogen receptor-positive breast cancer is subdivided into subtypes LuminalA and LuminalB, based on different expression patterns. MicroRNA-190b has been reported to be up-regulated in estrogen receptor-positive breast cancers. In this study we aimed to investigate the role of CpG promoter methylation in regulating miR-190b expression and its impact on clinical presentation and prognosis. DNA methylation analysis for the promotor of microRNA-190b was performed by pyrosequencing 549 primary breast tumors, of which 62 were carriers of the BRCA2999del5 founder mutation, 71 proximal normal breast samples and 16 breast derived cell lines. MicroRNA-190b expression was analysed in 67 primary breast tumors, 14 paired normal breast samples and 16 breast derived cell lines. Tissue microarrays (TMAs) were available for ER (n = 436), PR (n = 436), HER-2 (N = 258) and Ki67 (n = 248). MiR-190b had reduced promoter methylation in estrogen receptor-positive breast cancers (P = 1.02e–12, Median values: ER+ 24.3, ER– 38.26) and miR-190b’s expression was up-regulated in a correlative manner (P = 1.83e–06, Spearman’s rho –0.62). Through breast cancer specific survival analysis, we demonstrated that LuminalA patients exhibiting miR-190b hypo-methylation had better survival than other patients (P = 0.034, HR = 0.29, 95% CI 0.09-0.91). We, furthermore, demonstrated that miR-190b hypo-methylation occurs less frequently in ER+ tumors from BRCA2999del5 mutation carriers than in non-mutated individuals (P = 0.038, Χ2 = 4.32, n = 335). Our results suggest that upregulation of miR-190b may occur through loss of promoter DNA methylation during the development of estrogen-receptor (ER) positive breast cancers, and that miR-190b hypo-methylation leads to increased breast cancer specific survival within the LuminalA- subtype but not LuminalB.This work was funded b y Gongum Saman (EAF), The Icelandic cancer society (TG), and Icelandic Centre for Research RANNIS grant ID # 141395Peer reviewe