Models of the Pseudogap State of Two-Dimensional Systems

We analyze a number of ``nearly exactly'' solvable models of electronic spectrum of two-dimensional systems with well-developed fluctuations of short range order of ``dielectric'' (e.g. antiferromagnetic) or ``superconducting'' type, which lead to the formation of anisotropic pseudogap state on certain parts of the Fermi surface. We formulate a recurrence procedure to calculate one-electron Green's function which takes into account all Feynman diagrams in perturbation series and is based upon the approximate Ansatz for higher-order terms in this series. Detailed results for spectral densities and density of states are presented. We also discuss some important points concerning the justification of our Ansatz for higher-order contributions.Comment: 22 pages, 15 figures, RevTeX 3.0, Postscript figures attache

Phenomenological BCS theory of the high-TcT_c cuprates

A BCS model characterized by a phenomenological pair potential with on-site ($V_0$), nearest ($V_1$), and next nearest ($V_2$) neighbour coupling constants, and an empirical quasiparticle dispersion taken from angle-resolved photoemission spectra is considered. The model can consistently explain the experimental data concerning the pair state of the hole doped cuprates. Three ingredients are required to make the interpretation possible: the existence of flat bands, a very small effective on-site repulsion, and a slightly dominating effective nnn attraction $V_2$ of the order of 60-80meV with a ratio $V_2/V_1 \approx 1.5$.Comment: 13 pages, uuencoded Postscrip

Phenomenological Models for the Gap Anisotropy of Bi-2212 as Measured by ARPES

Recently, high resolution angle-resolved photoemission spectroscopy has been used to determine the detailed momentum dependence of the superconducting gap in the high temperature superconductor Bi-2212. In this paper, we first describe tight binding fits to the normal state dispersion and superlattice modulation effects. We then discuss various theoretical models in light of the gap measurements. We find that the simplest model which fits the data is the anisotropic s-wave gap $\cos(k_x)\cos(k_y)$, which within a one-band BCS frame- work suggests the importance of next near neighbor Cu-Cu interactions. Various alternative interpretations of the observed gap are also discussed, along with the implications for microscopic theories of high temperature superconductors.Comment: 14 pages, revtex, 9 uuencoded postscript figure

Anomalous Behavior Of The Complex Conductivity Of Y_{1-x}Pr_xBa_2Cu_3O_7 Observed With THz Spectroscopy

We have measured the electrodynamic properties of Y_{1-x}Pr_xBa_2Cu_3O_7 single crystal thin films as a function of temperature using coherent THz-time-domain spectroscopy. We obtain directly the complex conductivity $\sigma=\sigma_1+i\sigma_2$, the London penetration depth $\lambda_L$, the plasma frequency $\omega_p$, and the quasiparticle scattering rate $1/\tau$. We find that $1/\tau$ drops exponentially rapidly with $T$ below the critical temperature in {\em all} the superconducting samples, implying that this behavior is a {\em signature} of high-$T_c$ superconductivity. The plasma frequency decreases with increasing Pr content, providing evidence that Pr depletes carriers, leaving the CuO planes {\em underdoped}. Both the conductivity in the THz region and the dc resistivity yield evidence for the opening of a spin gap {\em above} $T_c$.Comment: 9 pages, REVTEX 3.

Superconducting Gap Anisotropy and Quasiparticle Interactions: a Doping Dependent ARPES Study

Comparing ARPES measurements on Bi2212 with penetration depth data, we show that a description of the nodal excitations of the d-wave superconducting state in terms of non-interacting quasiparticles is inadequate, and we estimate the magnitude and doping dependence of the Landau interaction parameter which renormalizes the linear T contribution to the superfluid density. Furthermore, although consistent with d-wave symmetry, the gap with underdoping cannot be fit by the simple coskx-cosky form, which suggests an increasing importance of long range interactions as the insulator is approached.Comment: 4 pages, 3 eps figs, manuscript and Fig. 3 significantly revise

Angle-resolved photoemission study of untwinned PrBa2_2Cu3_3O7_7: undoped CuO2_2 plane and doped CuO3_3 chain

We have performed an angle-resolved photoemission study on untwinned PrBa$_2$Cu$_3$O$_7$, which has low resistivity but does not show superconductivity. We have observed a dispersive feature with a band maximum around ($\pi$/2,$\pi$/2), indicating that this band is derived from the undoped CuO$_2$ plane. We have observed another dispersive band exhibiting one-dimensional character, which we attribute to signals from the doped CuO$_3$ chain. The overall band dispersion of the one-dimensional band agrees with the prediction of $t-J$ model calculation with parameters relevant to cuprates except that the intensity near the Fermi level is considerably suppressed in the experiment.Comment: 6 pages, 10 figure

Spatio-temporal dynamics and plastic flow of vortices in superconductors with periodic arrays of pinning sites

We present simulations of flux-gradient-driven superconducting rigid vortices interacting with square and triangular arrays of columnar pinning sites in an increasing external magnetic field. These simulations allow us to quantitatively relate spatio-temporal microscopic information of the vortex lattice with typically measured macroscopic quantities, such as the magnetization $M(H)$. The flux lattice does not become completely commensurate with the pinning sites throughout the sample at the magnetization matching peaks, but forms a commensurate lattice in a region close to the edge of the sample. Matching fields related to unstable vortex configurations do not produce peaks in $M(H)$. We observe a variety of evolving complex flux profiles, including flat terraces or plateaus separated by winding current-carrying strings and, near the peaks in $M(H)$, plateaus only in certain regions, which move through the sample as the field increases

Depletion of Kinesin 5B Affects Lysosomal Distribution and Stability and Induces Peri-Nuclear Accumulation of Autophagosomes in Cancer Cells

Background: Enhanced lysosomal trafficking is associated with metastatic cancer. In an attempt to discover cancer relevant lysosomal motor proteins, we compared the lysosomal proteomes from parental MCF-7 breast cancer cells with those from highly invasive MCF-7 cells that express an active form of the ErbB2 (DN-ErbB2). Methodology/Principal Findings: Mass spectrometry analysis identified kinesin heavy chain protein KIF5B as the only microtubule motor associated with the lysosomes in MCF-7 cells, and ectopic DN-ErbB2 enhanced its lysosomal association. KIF5B associated with lysosomes also in HeLa cervix carcinoma cells as analyzed by subcellular fractionation. The depletion of KIF5B triggered peripheral aggregations of lysosomes followed by lysosomal destabilization, and cell death in HeLa cells. Lysosomal exocytosis in response to plasma membrane damage as well as fluid phase endocytosis functioned, however, normally in these cells. Both HeLa and MCF-7 cells appeared to express similar levels of the KIF5B isoform but the death phenotype was weaker in KIF5B-depleted MCF-7 cells. Surprisingly, KIF5B depletion inhibited the rapamycin-induced accumulation of autophagosomes in MCF-7 cells. In KIF5B-depleted cells the autophagosomes formed and accumulated in the close proximity to the Golgi apparatus, whereas in the control cells they appeared uniformly distributed in the cytoplasm. Conclusions/Significance: Our data identify KIF5B as a cancer relevant lysosomal motor protein with additional functions in autophagosome formatio

Preservation of quality of life in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial)

AIMS: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. METHODS: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3–9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. RESULTS: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. CONCLUSIONS: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases

Up-regulated expression of LAMP2 and autophagy activity during neuroendocrine differentiation of prostate cancer LNCaP cells

Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells. Using cDNA microarrays, we compared gene expression profiles of NE cells and non-differentiated LNCaP cells. We identified up-regulation of 155 genes, among them LAMP2, a lysosomal membrane protein involved in lysosomal stability and autophagy. We then confirmed up-regulation of LAMP2 in NE cells by qRT-PCR, Western blot and confocal microscopy assays, showing that mRNA up-regulation correlated with increased levels of LAMP2 protein. Subsequently, we determined autophagy activity in NE cells by assessing the protein levels of SQSTM/p62 and LC3 by Western blot and LC3 and Atg5 mRNAs content by qRT-PCR. The decreased levels of SQSTM/p62 was accompanied by an enhanced expression of LC3 and ATG5, suggesting activation of autophagy in NE cells. Blockage of autophagy with 1μM AKT inhibitor IV, or by silencing Beclin 1 and Atg5, prevented NE cell differentiation, as revealed by decreased levels of the NE markers. In addition, AKT inhibitor IV as well as Beclin1 and Atg5 kwockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these results suggest that LAMP2 overexpression assists NE differentiation of LNCaP cells induced by serum deprivation and facilitates autophagy activity in order to attain the NE phenotype and cell survival. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer