Exciton spectroscopy of hexagonal boron nitride using non-resonant x-ray Raman scattering

We report non-resonant x-ray Raman scattering (XRS) measurements from hexagonal boron nitride for transferred momentum from 2 to 9 $\mathrm{\AA}^{-1}$ along directions both in and out of the basal plane. A symmetry-based argument, together with real-space full multiple scattering calculations of the projected density of states in the spherical harmonics basis, reveals that a strong pre-edge feature is a dominantly $Y_{10}$-type Frenkel exciton with no other \textit{s}-, \textit{p}-, or \textit{d}- components. This conclusion is supported by a second, independent calculation of the \textbf{q}-dependent XRS cross-section based on the Bethe-Salpeter equation

Anisotropic excitonic effects in the energy loss function of hexagonal boron nitride

We demonstrate that the valence energy-loss function of hexagonal boron nitride (hBN) displays a strong anisotropy in shape, excitation energy and dispersion for momentum transfer q parallel or perpendicular to the hBN layers. This is manifested by e.g. an energy shift of 0.7 eV that cannot be captured by single-particle approaches and is a demonstration of a strong anisotropy in the two-body electron-hole interaction. Furthermore, for in-plane directions of q we observe a splitting of the -plasmon in the M direction that is absent in the K direction and this can be traced back to band-structure effects.Comment: 10 pages, 4 figure

A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2. HER2 targeting by antibodies inhibited growth in association with persistent generation of reactive oxygen species (ROS), glutathione (GSH) depletion, reduction in NRF2 levels and inhibition of NRF2 function in ovarian cancer cell lines. The combination of antibodies produced more potent effects than single alone; downregulated NRF2 substrates by repressing the Antioxidant Response (AR) pathway with concomitant transcriptional inhibition of NRF2. We showed the antibody combination produced increased methylation at the NRF2 promoter consistent with repression of NRF2 antioxidant function, as HDAC and methylation inhibitors reversed such produced transcriptional effects. These findings demonstrate a novel mechanism and role for NRF2 in mediating the response of cancer cells to the combination of Trastuzumab and Pertuzumab and reinforce the importance of NRF2 in drug resistance and as a key anticancer target

Systems analysis of drug-induced receptor tyrosine kinase reprogramming following targeted mono- and combination anti-cancer therapy

The receptor tyrosine kinases (RTKs) are key drivers of cancer progression and targets for drug therapy. A major challenge in anti-RTK treatment is the dependence of drug effectiveness on co-expression of multiple RTKs which defines resistance to single drug therapy. Reprogramming of the RTK network leading to alteration in RTK co-expression in response to drug intervention is a dynamic mechanism of acquired resistance to single drug therapy in many cancers. One route to overcome this resistance is combination therapy. We describe the results of a joint in silico, in vitro, and in vivo investigations on the efficacy of trastuzumab, pertuzumab and their combination to target the HER2 receptors. Computational modelling revealed that these two drugs alone and in combination differentially suppressed RTK network activation depending on RTK co-expression. Analyses of mRNA expression in SKOV3 ovarian tumour xenograft showed up-regulation of HER3 following treatment. Considering this in a computational model revealed that HER3 up-regulation reprograms RTK kinetics from HER2 homodimerisation to HER3/HER2 heterodimerisation. The results showed synergy of the trastuzumab and pertuzumab combination treatment of the HER2 overexpressing tumour can be due to an independence of the combination effect on HER3/HER2 composition when it changes due to drug-induced RTK reprogramming

NMR relaxation time around a vortex in stripe superconductors

Site-dependent NMR relaxation time $T_1({\bf r})$ is calculated in the vortex state using the Bogoliubov-de Gennes theory, taking account of possible "field-induced stripe'' states in which the magnetism arises locally around a vortex core in d-wave superconductivity. The recently observed huge enhancement $T_1^{-1}({\bf r})$ below $T_c$ at a core site in Tl$_2$Ba$_2$CuO$_6$ is explained. The field-induced stripe picture explains consistently other relevant STM and neutron experiments.Comment: 4 pages, 4 figure

The Effects of Phase Separation in the Cuprate Superconductors

Phase separation has been observed by several different experiments and it is believed to be closely related with the physics of cuprates but its exactly role is not yet well known. We propose that the onset of pseudogap phenomenon or the upper pseudogap temperature $T^*$ has its origin in a spontaneous phase separation transition at the temperature $T_{ps}=T^*$. In order to perform quantitative calculations, we use a Cahn-Hilliard (CH) differential equation originally proposed to the studies of alloys and on a spinodal decomposition mechanism. Solving numerically the CH equation it is possible to follow the time evolution of a coarse-grained order parameter which satisfies a Ginzburg-Landau free-energy functional commonly used to model superconductors. In this approach, we follow the process of charge segregation into two main equilibrium hole density branches and the energy gap normally attributed to the upper pseudogap arises as the free-energy potential barrier between these two equilibrium densities below $T_{ps}$. This simulation provides quantitative results %on the hole doping and temperature %dependence of the degree of the charge inhomogeneity in agreement with %some experiments and the simulations reproduce the observed stripe and granular pattern of segregation. Furthermore, with a Bogoliubov-deGennes (BdG) local superconducting critical temperature calculation for the lower pseudogap or the onset of local superconductivity, it yields novel interpretation of several non-conventional measurements on cuprates.Comment: Published versio

Insight, cognition and quality of life in Alzheimer's disease

Background: The detrimental impact of dementia upon patient health-related quality of life (HRQL) is well established, as is the importance of improving HRQL. However, relatively little is known about the natural history of HRQL in dementia and those factors influencing it. This limited knowledge potentially restricts the evaluation of the efficacy of interventions designed to improve HRQL. One such area concerns the relationship between HRQL and patient insight. It remains unclear what impact, if any, impaired insight has upon a patient's HRQL. The present study aimed to investigate the relationship between insight and HRQL in a sample of patients with Alzheimer's disease (AD) and their carers. Methods: 256 patients with AD were recruited as part of AddNeuroMed, a multicentre European AD biomarkers study. Of these, 174 completed a quality-of-life measure in addition to a comprehensive battery of clinical and neuropsychological assessments. Results: Insight was found to be differentially related to patient perceptions of HRQL in mild and moderate dementia. Within moderate dementia, impaired insight was associated with better perceived HRQL. Conversely, cognition, but not insight, was associated with impaired HRQL in mild dementia. Insight was not found to be associated with carer perceptions of patient HRQL. Conclusion: Impairment of insight is associated with better HRQL in moderate dementia. This finding has implications for interventions which focus on increasing patient awareness and orientation, as impairment of insight appears to have a positive impact upon HRQL

Field induced dx2−y2+idxyd_{x^2-y^2}+id_{xy} state and marginal stability of high-Tc superconductors

It is shown that the {\em complex} $d_{xy}$ component is generated in d-wave superconductor in the magnetic field. As one enters superconducting state at finite field the normal to superconducting transition occurs into bulk $d_{x^2-y^2}+i d_{xy}$ state . The driving force for the transition is the linear coupling between magnetic field and non zero magnetization of the $d_{x^2-y^2}+i d_{xy}$ condensate. The external magnetic field violates parity and time reversal symmetries and the nodal quasiparticle states respond by generating the $id_{xy}$ component of the order parameter, with the magnitude estimated to be on the order of few Kelvin. Parity (P) and time reversal (T) symmetries are violated in this state.Comment: 4 pages, latex file with two eps figure file

X-ray Raman scattering study of aligned polyfluorene

We present a non-resonant inelastic x-ray scattering study at the carbon K-edge on aligned poly[9,9-bis(2-ethylhexyl)-fluorene-2,7-diyl] and show that the x-ray Raman scattering technique can be used as a practical alternative to x-ray absorption measurements. We demonstrate that this novel method can be applied to studies on aligned $\pi$-conjugated polymers complementing diffraction and optical studies. Combining the experimental data and a very recently proposed theoretical scheme we demonstrate a unique property of x-ray Raman scattering by performing the symmetry decomposition on the density of unoccupied electronic states into $s$- and $p$-type symmetry contributions.Comment: 19 pages, 8 figure