Pair-Hopping Mechanism for Layered Superconductors

We propose a possible charge fluctuation effect expected in layered superconducting materials. In the multireference density functional theory, relevant fluctuation channels for the Josephson coupling between superconducting layers include the interlayer pair hopping derived from the Coulomb repulsion. When interlayer single-electron tunneling processes are irrelevant in the Kohn-Sham electronic band structure calculation, the two-body effective interactions stabilize a superconducting phase. This state is also regarded as a valence-bond solid in a bulk electronic state. The hidden order parameters coexist with the superconducting order parameter when the charging effect of a layer is comparable to the pair hopping. Relevant materials structures favorable for the pair-hopping mechanism are discussed.Comment: 24 pages, 2 figures, to be published in J. Phys. Soc. Jpn. (2009

A topological insulator surface under strong Coulomb, magnetic and disorder perturbations

Three dimensional topological insulators embody a newly discovered state of matter characterized by conducting spin-momentum locked surface states that span the bulk band gap as demonstrated via spin-resolved ARPES measurements . This highly unusual surface environment provides a rich ground for the discovery of novel physical phenomena. Here we present the first controlled study of the topological insulator surfaces under strong Coulomb, magnetic and disorder perturbations. We have used interaction of iron, with a large Coulomb state and significant magnetic moment as a probe to \textit{systematically test the robustness} of the topological surface states of the model topological insulator Bi$_2$Se$_3$. We observe that strong perturbation leads to the creation of odd multiples of Dirac fermions and that magnetic interactions break time reversal symmetry in the presence of band hybridization. We also present a theoretical model to account for the altered surface of Bi$_2$Se$_3$. Taken collectively, these results are a critical guide in manipulating topological surfaces for probing fundamental physics or developing device applications.Comment: 14 pages, 4 Figures. arXiv admin note: substantial text overlap with arXiv:1009.621

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

Anti-inflammatory effect of euphane- and tirucallane-type triterpenes isolated from the traditional herb Euphorbia neriifolia L

The Euphorbiaceae plant Euphorbia neriifolia L. is distributed widely in India, Thailand, Southeastern China, and Taiwan and used as a carminative and expectorant to treat several inflammation-related diseases, such as gonorrhoea, asthma, and cancer. In the course of our search for potential anti-inflammatory agents from the titled plant, 11 triterpenes from the stem of E. neriifolia were isolated and reported in our previous endeavor. Given its rich abundance in triterpenoids, the ethanolic extract in this follow-up exploration has led to the isolation of additional eight triterpenes, including six new euphanes—neritriterpenols H and J–N (1 and 3–7)—one new tirucallane, neritriterpenol I (2), and a known compound, 11-oxo-kansenonol (8). Their chemical structures were elucidated on the basis of spectroscopic data, including 1D- and 2D NMR, and HRESIMS spectra. The absolute stereochemistry of neritriterpenols was determined by single-crystal X-ray diffraction analysis, ICD spectra, and DP4+ NMR data calculations. Compounds 1–8 were also evaluated for their anti-inflammatory activity by using lipopolysaccharide (LPS)-stimulated IL-6 and TNF-α on RAW 264.7 macrophage cells. Intriguingly, the euphane-type triterpenes (1 and 3–8) showed an inhibitory effect on LPS-induced IL-6 but not on TNF-α, while tirucallane-type triterpene 2 showed strong inhibition on both IL-6 and TNF-α

The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions

The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members in human, several of which are distinctly expressed and functionally involved in polymorphonuclear cells (PMNs). As former work indicated the possible presence of the aGPCR GPR97 in granulocytes, we studied its cellular distribution, molecular structure, signal transduction, and biological function in PMNs. RNA sequencing and mass-spectrometry revealed abundant RNA and protein expression of ADGRG3/GPR97 in granulocyte precursors and terminally differentiated neutrophilic, eosinophilic, and basophilic granulocytes. Using a newly generated GPR97-specific monoclonal antibody, we confirmed that endogenous GPR97 is a proteolytically processed, dichotomous, N-glycosylated receptor. GPR97 was detected in tissue-infiltrating PMNs and upregulated during systemic inflammation. Antibody ligation of GPR97 increased neutrophil reactive oxygen species production and proteolytic enzyme activity, which is accompanied by an increase in mitogen-activated protein kinases and IκBα phosphorylation. In-depth analysis of the GPR97 signaling cascade revealed a possible switch from basal Gαs/cAMP-mediated signal transduction to a Gαi-induced reduction in cAMP levels upon mutation-induced activation of the receptor, in combination with an increase in downstream effectors of Gβγ, such as SRE and NF-κB. Finally, ligation of GPR97 increased the bacteria uptake and killing activity of neutrophils. We conclude that the specific presence of GPR97 regulates antimicrobial activity in human granulocytes

Host-dependent Lewis (Le) antigen expression in Helicobacter pylori cells recovered from Leb-transgenic mice

Variation of surface antigen expression is a mechanism used by microbes to adapt to and persist within their host habitats. Helicobacter pylori, a persistent bacterial colonizer of the human stomach, can alter its surface Lewis (Le) antigen expression. We examined H. pylori colonization in mice to test the hypothesis that host phenotype selects for H. pylori (Le) phenotypes. When wild-type and Leb-expressing transgenic FVB/N mice were challenged with H. pylori strain HP1, expressing Lex and Ley, we found that bacterial populations recovered after 8 mo from Leb-transgenic, but not wild-type, mice expressed Leb. Changes in Le phenotype were linked to variation of a putative galactosyltransferase gene (β-(1,3)galT); mutagenesis and complementation revealed its essential role in type I antigen expression. These studies indicate that H. pylori evolves to resemble the host's gastric Le phenotype, and reveal a bacterial genetic locus that is subject to host-driven selection pressure