Smoothened adopts multiple active and inactive conformations capable of trafficking to the primary cilium.

Activation of Hedgehog (Hh) signaling requires the transmembrane protein Smoothened (Smo), a member of the G-protein coupled receptor superfamily. In mammals, Smo translocates to the primary cilium upon binding of Hh ligands to their receptor, Patched (Ptch1), but it is unclear if ciliary trafficking of Smo is sufficient for pathway activation. Here, we demonstrate that cyclopamine and jervine, two structurally related inhibitors of Smo, force ciliary translocation of Smo. Treatment with SANT-1, an unrelated Smo antagonist, abrogates cyclopamine- and jervine-mediated Smo translocation. Further, activation of protein kinase A, either directly or through activation of Galphas, causes Smo to translocate to a proximal region of the primary cilium. We propose that Smo adopts multiple inactive and active conformations, which influence its localization and trafficking on the primary cilium

Equilibrium vortex formation in ultrarapidly rotating two-component Bose-Einstein condensates

Equilibrium vortex formation in rotating binary Bose gases with a rotating frequency higher than the harmonic trapping frequency is investigated theoretically. We consider the system being evaporatively cooled to form condensates and a combined numerical scheme is applied to ensure the binary system being in an authentic equilibrium state. To keep the system stable against the large centrifugal force of ultrafast rotation, a quartic trapping potential is added to the existing harmonic part. Using the Thomas-Fermi approximation, a critical rotating frequency \Omega_c is derived, which characterizes the structure with or without a central density hole. Vortex structures are studied in detail with rotation frequency both above and below ?\Omega_c and with respect to the miscible, symmetrically separated, and asymmetrically separated phases in their nonrotating ground-state counterparts.Comment: 7 pages, 7 figure

Systematic errors in strong gravitational lensing reconstructions, a numerical simulation perspective

We present the analysis of a sample of twenty-four SLACS-like galaxy-galaxy strong gravitational lens systems with a background source and deflectors from the Illustris-1 simulation. We study the degeneracy between the complex mass distribution of the lenses, substructures, the surface brightness distribution of the sources, and the time delays. Using a novel inference framework based on Approximate Bayesian Computation, we find that for all the considered lens systems, an elliptical and cored power-law mass density distribution provides a good fit to the data. However, the presence of cores in the simulated lenses affects most reconstructions in the form of a Source Position Transformation. The latter leads to a systematic underestimation of the source sizes by 50 per cent on average, and a fractional error in $H_{0}$ of around $25_{-19}^{+37}$ per cent. The analysis of a control sample of twenty-four lens systems, for which we have perfect knowledge about the shape of the lensing potential, leads to a fractional error on $H_{0}$ of $12_{-3}^{+6}$ per cent. We find no degeneracy between complexity in the lensing potential and the inferred amount of substructures. We recover an average total projected mass fraction in substructures of $f_{\rm sub}<1.7-2.0\times10^{-3}$ at the 68 per cent confidence level in agreement with zero and the fact that all substructures had been removed from the simulation. Our work highlights the need for higher-resolution simulations to quantify the lensing effect of more realistic galactic potentials better, and that additional observational constraint may be required to break existing degeneracies.Comment: Accepted by MNRA

Spontaneous Crystallization of Skyrmions and Fractional Vortices in the Fast-rotating and Rapidly-quenched Spin-1 Bose-Einstein Condensates

We investigate the spontaneous generation of crystallized topological defects via the combining effects of fast rotation and rapid thermal quench on the spin-1 Bose-Einstein condensates. By solving the stochastic projected Gross-Pitaevskii equation, we show that, when the system reaches equilibrium, a hexagonal lattice of skyrmions, and a square lattice of half-quantized vortices can be formed in a ferromagnetic and antiferromagnetic spinor BEC, respetively, which can be imaged by using the polarization-dependent phase-contrast method

The Pharmacological Effects and Pharmacokinetics of Active Compounds of Artemisia capillaris.

Artemisia capillaris Thunb. (A.capillaris, Yin-Chen in Chinese) is a traditional medicinal herb with a wide spectrum of pharmacological properties ranging from effects against liver dysfunction to treatments of severe cirrhosis and cancer. We used relevant keywords to search electronic databases, including PubMed, Medline, and Google Scholar, for scientific contributions related to this medicinal herb and the pharmacokinetics of its components. The pharmaceutical effects of A.capillaris contribute to the treatment not only of viral hepatitis, cirrhosis, and hepatocellular hepatoma, but also metabolic syndrome, psoriasis, and enterovirus in the clinic. The bioactive compounds, including scoparone, capillarisin, scopoletin, and chlorogenic acid, exhibit antioxidant, anti-inflammatory, antisteatotic, antiviral, and antitumor properties, reflecting the pharmacological effects of A.capillaris. The pharmacokinetics of the main bioactive compounds in A. capillaris can achieve a maximum concentration within 1 hour, but only chlorogenic acid has a relatively long half-life. Regarding the use of the A. capillaris herb by health professionals to treat various diseases, the dosing schedule of this herb should be carefully considered to maximize therapeutic outcomes while lessening possible side effects

Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report

We report a 49-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen. He underwent esophagogastroduodenoscopy in September 2009, which revealed a 2-cm gastric ulcer on the lesser curvature proximal to angularis. Biopsy of gastric ulcer showed moderately differentiated adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and fluorescence in situ hybridization. Further workups with endoscopic ultrasound, computed tomography and positron emission tomography staged his cancer as T3N1M0. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, docetaxel and capecitabine without severe toxicities except grade 2 diarrhea near the completion of cycle 3 requiring discontinuation of capecitabine. Afterwards, he received total gastrectomy with extended D2 lymph node dissections showing pathological complete response. He went on to receive 3 more cycles of chemotherapy postoperatively. The role of trastuzumab as a part of perioperative therapy in gastric cancer overexpressing HER2 is worth further investigation