Spin-dependent THz oscillator based on hybrid graphene superlattices

We theoretically study the occurrence of Bloch oscillations in biased hybrid graphene systems with spin-dependent superlattices. The spin-dependent potential is realized by a set of ferromagnetic insulator strips deposited on top of a gapped graphene nanoribbon, which induce a proximity exchange splitting of the electronic states in the graphene monolayer. We numerically solve the Dirac equation and study Bloch oscillations in the lowest conduction band of the spin-dependent superlattice. While the Bloch frequency is the same for both spins, we find the Bloch amplitude to be spin dependent. This difference results in a spin-polarized ac electric current in the THz range.Comment: 4 pages, 6 figure

Anisotropic thermal emission from magnetized neutron stars

The thermal emission from isolated neutron stars is not well understood. The X-ray spectrum is very close to a blackbody but there is a systematic optical excess flux with respect to the extrapolation to low energy of the best blackbody fit. This fact, in combination with the observed pulsations in the X-ray flux, can be explained by anisotropies in the surface temperature distribution.We study the thermal emission from neutron stars with strong magnetic fields in order to explain the origin of the anisotropy. We find (numerically) stationary solutions in axial symmetry of the heat transportequations in the neutron star crust and the condensed envelope. The anisotropy in the conductivity tensor is included consistently. The presence of magnetic fields of the expected strength leads to anisotropy in the surface temperature. Models with toroidal components similar to or larger than the poloidal field reproduce qualitatively the observed spectral properties and variability of isolated neutron stars. Our models also predict spectral features at energies between 0.2 and 0.6 keV.Comment: 18 pages, 19 figures, version accepted for publication in A&

Inhibiting CDK4/6 in pancreatic ductal adenocarcinoma via microRNA-21

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a 5-year survival rate of 5–10 %. The high mortality rate is due to the asymptomatic progression of clinical features in metastatic stages of the disease, which renders standard therapeutic options futile. PDAC is characterised by alterations in several genes that drive carcinogenesis and limit therapeutic response. The two most common genetic aberrations in PDAC are the mutational activation of KRAS and loss of the tumour suppressor CDK inhibitor 2A (CDKN2A), which culminate the activation of the cyclin-dependent kinase 4 and 6 (CDK4/6), that promote G1 cell cycle progression. Therapeutic strategies focusing on the CDK4/6 inhibitors such as palbociclib (PD-0332991) may potentially improve outcomes in this malignancy. MicroRNAs (miRs/miRNAs) are small endogenous non-coding RNA molecules associated with cellular proliferation, invasion, apoptosis, and cell cycle. Primarily, miR-21 promotes cell proliferation and a higher proportion of PDAC cells in the S phase, while knockdown of miR-21 has been linked to cell cycle arrest at the G2/M phase and inhibition of cell proliferation. In this study, using a CRISPR/Cas9 loss-of-function screen, we individually silenced the expression of miR-21 in two PDAC cell lines and in combination with PD-0332991 treatment, we examined the synergetic mechanisms of CDK4/6 inhibitors and miR-21 knockouts (KOs) on cell survival and death. This combination reduced cell proliferation, cell viability, increased apoptosis and G1 arrest in vitro. We further analysed the mitochondrial respiration and glycolysis of PDAC cells; then assessed the protein content of these cells and revealed numerous Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with PD-0332991 treatment and miR-21 knocking out. Our results demonstrate that combined targeting of CDK4/6 and silencing of miR-21 represents a novel therapeutic strategy in PDAC

Store-operated interactions between plasmalemmal STIM1 and TRPC1 proteins stimulate PLCβ1 to induce TRPC1 channel activation in vascular smooth muscle cells.

KEY POINTS: Depletion of Ca(2+) stores activates store-operated channels (SOCs), which mediate Ca(2+) entry pathways that regulate cellular processes such as contraction, proliferation and gene expression. In vascular smooth muscle cells (VSMCs), stimulation of SOCs composed of canonical transient receptor potential channel 1 (TRPC1) proteins requires G protein α q subunit (Gαq)/phospholipase C (PLC)β1/protein kinase C (PKC) activity. We studied the role of stromal interaction molecule 1 (STIM1) in coupling store depletion to this activation pathway using patch clamp recording, GFP-PLCδ1-PH imaging and co-localization techniques. Store-operated TRPC1 channel and PLCβ1 activities were inhibited by STIM1 short hairpin RNA (shRNA) and absent in TRPC1(-/-) cells, and store-operated PKC phosphorylation of TRPC1 was inhibited by STIM1 shRNA. Store depletion induced interactions between STIM1 and TRPC1, Gαq and PLCβ1, which required STIM1 and TRPC1. Similar effects were produced with noradrenaline. These findings identify a new activation mechanism of TRPC1-based SOCs in VSMCs, and a novel role for STIM1, where store-operated STIM1-TRPC1 interactions stimulate Gαq/PLCβ1/PKC activity to induce channel gating. ABSTRACT: In vascular smooth muscle cells (VSMCs), stimulation of canonical transient receptor potential channel 1 (TRPC1) protein-based store-operated channels (SOCs) mediates Ca(2+) entry pathways that regulate contractility, proliferation and migration. It is therefore important to understand how these channels are activated. Studies have shown that stimulation of TRPC1-based SOCs requires G protein α q subunit (Gαq)/phospholipase C (PLC)β1 activities and protein kinase C (PKC) phosphorylation, although it is unclear how store depletion stimulates this gating pathway. The present study examines this issue by focusing on the role of stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum Ca(2+) sensor. Store-operated TRPC1 channel activity was inhibited by TRPC1 and STIM1 antibodies and STIM1 short hairpin RNA (shRNA) in wild-type VSMCs, and was absent in TRPC1(-/-) VSMCs. Store-operated PKC phosphorylation of TRPC1 was reduced by knockdown of STIM1. Moreover, store-operated PLCβ1 activity measured with the fluorescent phosphatidylinositol 4,5-bisphosphate/inositol 1,4,5-trisphosphate biosensor GFP-PLCδ1-PH was reduced by STIM1 shRNA and absent in TRPC1(-/-) cells. Immunocytochemistry, co-immunoprecipitation and proximity ligation assays revealed that store depletion activated STIM1 translocation from within the cell to the plasma membrane (PM) where it formed STIM1-TRPC1 complexes, which then associated with Gαq and PLCβ1. Noradrenaline also evoked TRPC1 channel activity and associations between TRPC1, STIM1, Gαq and PLCβ1, which were inhibited by STIM1 knockdown. Effects of N-terminal and C-terminal STIM1 antibodies on TRPC1-based SOCs and STIM1 staining suggest that channel activation may involve insertion of STIM1 into the PM. The findings of the present study identify a new activation mechanism of TRPC1-based SOCs in VSMCs, and a novel role for STIM1, in which store-operated STIM1-TRPC1 interactions stimulate PLCβ1 activity to induce PKC phosphorylation of TRPC1 and channel gating

Z_2-gradings of Clifford algebras and multivector structures

Let Cl(V,g) be the real Clifford algebra associated to the real vector space V, endowed with a nondegenerate metric g. In this paper, we study the class of Z_2-gradings of Cl(V,g) which are somehow compatible with the multivector structure of the Grassmann algebra over V. A complete characterization for such Z_2-gradings is obtained by classifying all the even subalgebras coming from them. An expression relating such subalgebras to the usual even part of Cl(V,g) is also obtained. Finally, we employ this framework to define spinor spaces, and to parametrize all the possible signature changes on Cl(V,g) by Z_2-gradings of this algebra.Comment: 10 pages, LaTeX; v2 accepted for publication in J. Phys.