Phase separation near half-filling point in superconducting compounds

We present the model of superconducting ceramics using the single band extended Hubbard Hamiltonian. We investigate the simultaneous presence of antiferromagnetism (AF) and d-wave superconductivity (SC) in the coherent potential (CP) approximation applied to the on-site Coulomb repulsion $U$. We consider the hopping interaction, $\Delta t$, the inter-site charge-charge interaction, $V$, (creating SC), and the single site Hund's type exchange interaction, $F_{in}$, (creating AF). The influence of these interactions on the separation of superconducting and antiferromagnetic phases near the half-filling point is investigated. Results are compared with the experimental data for YBaCuO and NdCeCuO compounds.Comment: 4 pages, 4 figure

Band magnetism with inter-site correlations and interactions

We introduce the Hamiltonian to describe narrow band electrons. The physics of driving forces towards ferromagnetism is re-examined. Using different approximations it has been shown that the magnetic moments created by inter-site interaction and inter-site kinetic correlation decrease quickly with temperature. As a result of these interactions and the realistic density of states (DOS) the Curie temperatures calculated after fitting magnetic moments to their low temperature values are realistic. In the past the Curie temperatures calculated using only the on-site interaction were much higher than the experimental temperatures.Comment: 6 pages, 1 figur

Treating breast cancer through novel inhibitors of the phosphatidylinositol 3'-kinase pathway

Recent studies indicate that constitutive signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is a cause of treatment resistance in breast cancer patients. This implies that patients with tumors that exhibit aberrant PI3K signaling may benefit from targeted pathway inhibitors. The first agents to make it to the clinic are the rapamycin analogs. These compounds inhibit the downstream PI3K effector mTOR (mammalian target of rapamycin). A study presented in this issue of Breast Cancer Research suggests that recently developed inhibitors of phosphoinositide-dependent protein kinase 1, a more proximal target of the PI3K pathway, may provide an alternative route to effective PI3K pathway inhibition for breast cancer treatment

COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

<p>Abstract</p> <p>Background</p> <p>Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation.</p> <p>Methods</p> <p>Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival.</p> <p>Results</p> <p>COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196.</p> <p>Conclusions</p> <p>Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.</p

Timing the initiation of multiple myeloma

The evolution and progression of multiple myeloma and its precursors over time is poorly understood. Here, we investigate the landscape and timing of mutational processes shaping multiple myeloma evolution in a large cohort of 89 whole genomes and 973 exomes. We identify eight processes, including a mutational signature caused by exposure to melphalan. Reconstructing the chronological activity of each mutational signature, we estimate that the initial transformation of a germinal center B-cell usually occurred during the first 2nd-3rd decades of life. We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection

Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions

Abstract: The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is of concern for their clinical application. However, the effect of different culture conditions on the underlying mutation rate is unknown. Here we show that the mutation rate in two human embryonic stem cell lines derived and banked for clinical application is low and not substantially affected by culture with Rho Kinase inhibitor, commonly used in their routine maintenance. However, the mutation rate is reduced by >50% in cells cultured under 5% oxygen, when we also found alterations in imprint methylation and reversible DNA hypomethylation. Mutations are evenly distributed across the chromosomes, except for a slight increase on the X-chromosome, and an elevation in intergenic regions suggesting that chromatin structure may affect mutation rate. Overall the results suggest that pluripotent stem cells are not subject to unusually high rates of genetic or epigenetic alterations

PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts

Stalled replication forks can be restarted and repaired by RAD51-mediated homologous recombination (HR), but HR can also perform post-replicative repair after bypass of the obstacle. Bulky DNA adducts are important replication-blocking lesions, but it is unknown whether they activate HR at stalled forks or behind ongoing forks. Using mainly BPDE-DNA adducts as model lesions, we show that HR induced by bulky adducts in mammalian cells predominantly occurs at post-replicative gaps formed by the DNA/RNA primase PrimPol. RAD51 recruitment under these conditions does not result from fork stalling, but rather occurs at gaps formed by PrimPol re-priming and resection by MRE11 and EXO1. In contrast, RAD51 loading at double-strand breaks does not require PrimPol. At bulky adducts, PrimPol promotes sister chromatid exchange and genetic recombination. Our data support that HR at bulky adducts in mammalian cells involves post-replicative gap repair and define a role for PrimPol in HR-mediated DNA damage tolerance

The Influence of Potential Energy Shape on the Total Electrical Efficiency of the Energy Harvester

In this theoretical work we analyze the total effective electric power versus base acceleration amplitude generated by the energy harvesting system with an electromagnetic transducer. We compare the results for both linear and nonlinear case. The transition from linear to nonlinear behavior of the system can be achieved by the change of device geometry. To improve the power efficiency of our device we also examine the dependence of crossover point of acceleration amplitudes where generated power in the nonlinear system starts to exceed the generated power in the linear regime. We have found that the crossover point can be moved towards relatively small base acceleration values by appropriate selection of system nonlinearity "strength"