Interference effects in the photorecombination of argonlike Sc3+ ions: Storage-ring experiment and theory

Absolute total electron-ion recombination rate coefficients of argonlike Sc3+(3s2 3p6) ions have been measured for relative energies between electrons and ions ranging from 0 to 45 eV. This energy range comprises all dielectronic recombination resonances attached to 3p -> 3d and 3p -> 4s excitations. A broad resonance with an experimental width of 0.89 +- 0.07 eV due to the 3p5 3d2 2F intermediate state is found at 12.31 +- 0.03 eV with a small experimental evidence for an asymmetric line shape. From R-Matrix and perturbative calculations we infer that the asymmetric line shape may not only be due to quantum mechanical interference between direct and resonant recombination channels as predicted by Gorczyca et al. [Phys. Rev. A 56, 4742 (1997)], but may partly also be due to the interaction with an adjacent overlapping DR resonance of the same symmetry. The overall agreement between theory and experiment is poor. Differences between our experimental and our theoretical resonance positions are as large as 1.4 eV. This illustrates the difficulty to accurately describe the structure of an atomic system with an open 3d-shell with state-of-the-art theoretical methods. Furthermore, we find that a relativistic theoretical treatment of the system under study is mandatory since the existence of experimentally observed strong 3p5 3d2 2D and 3p5 3d 4s 2D resonances can only be explained when calculations beyond LS-coupling are carried out.Comment: 11 pages, 7 figures, 3 tables, Phys. Rev. A (in print), see also: http://www.strz.uni-giessen.de/~k

Targeting cholesterol-rich microdomains to circumvent tamoxifen-resistant breast cancer

Adjuvant treatment with tamoxifen substantially improves survival of women with estrogen-receptor positive (ER+) tumors. Tamoxifen resistance (TAMR) limits clinical benefit. RRR alpha tocopherol ether-linked acetic acid analogue (alpha-TEA) is a small bioactive lipid with potent anticancer activity. We evaluated the ability of alpha-TEA in the presence of tamoxifen to circumvent TAMR in human breast cancer cell lines. Methods: Two genotypically matched sets of TAM-sensitive (TAMS) and TAM-resistant (TAMR) human breast cancer cell lines were assessed for signal-transduction events with Western blotting, apoptosis induction with Annexin V-FITC/PI assays, and characterization of cholesterol-rich microdomains with fluorescence staining. Critical involvement of selected mediators was determined by using RNA interference and chemical inhibitors. Results: Growth-factor receptors (total and phosphorylated forms of HER-1 and HER-2), their downstream prosurvival mediators pAkt, pmTOR, and pERK1/2, phosphorylated form of estrogen receptor-alpha (pER-alpha at Ser-167 and Ser-118, and cholesterol-rich lipid microdomains were highly amplified in TAMR cell lines and enhanced by treatment with TAM. alpha-TEA disrupted cholesterol-rich microdomains, acted cooperatively with TAM to reduce prosurvival mediators, and induced DR5-mediated mitochondria-dependent apoptosis via an endoplasmic reticulum stress-triggered pro-death pJNK/CHOP/DR5 amplification loop. Furthermore, methyl-beta-cyclodextrin (M beta CD), a chemical disruptor of cholesterol rich microdomains, acted cooperatively with TAM to reduce prosurvival mediators and to induce apoptosis. Conclusions: Data for the first time document that targeting cholesterol-rich lipid microdomains is a potential strategy to circumvent TAMR, and the combination of alpha-TEA + TAM can circumvent TAMR by suppression of prosurvival signaling via disruption of cholesterol-rich lipid microdomains and activation of apoptotic pathways via induction of endoplasmic reticulum stress.Clayton Foundation for ResearchCenter for Molecular and Cellular Toxicology at the University of TexasNIEHS/NIH T32 ES07247Nutritional Science

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7–9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Analyzing and Biasing Simulations with PLUMED

This chapter discusses how the PLUMED plugin for molecular dynamics can be used to analyze and bias molecular dynamics trajectories. The chapter begins by introducing the notion of a collective variable and by then explaining how the free energy can be computed as a function of one or more collective variables. A number of practical issues mostly around periodic boundary conditions that arise when these types of calculations are performed using PLUMED are then discussed. Later parts of the chapter discuss how PLUMED can be used to perform enhanced sampling simulations that introduce simulation biases or multiple replicas of the system and Monte Carlo exchanges between these replicas. This section is then followed by a discussion on how free-energy surfaces and associated error bars can be extracted from such simulations by using weighted histogram and block averaging techniques

First measurement of the Michel parameter ξ′\xi^\prime in the τ−→μ−νˉμντ\tau^-\to\mu^-\bar{\nu}_\mu\nu_\tau decay at Belle

We report the first measurement of the Michel parameter $\xi^\prime$ in the $\tau^-\to\mu^-\bar{\nu}_\mu\nu_\tau$ decay with a new method proposed just recently. The measurement is based on the reconstruction of the $\tau^-\to\mu^-\bar{\nu}_\mu\nu_\tau$ events with subsequent muon decay-in-flight in the Belle central drift chamber. The analyzed data sample of $988\,\text{fb}^{-1}$ collected by the Belle detector corresponds to approximately $912\times10^6$ $\tau^+ \tau^-$ pairs. We measure $\xi^\prime=0.22\pm0.94(\text{stat})\pm0.42(\text{syst})$, which is in agreement with the Standard Model prediction of $\xi^\prime=1$. Statistical uncertainty dominates in this study, being a limiting factor, while systematic uncertainty is well under control. Our analysis proved the practicability of this promising method and its prospects for further precise measurement in future experiments.Comment: 6 pages, 4 figures, submitted to Phys. Rev. Let

Large Scale Benchmark of Materials Design Methods

Lack of rigorous reproducibility and validation are major hurdles for scientific development across many fields. Materials science in particular encompasses a variety of experimental and theoretical approaches that require careful benchmarking. Leaderboard efforts have been developed previously to mitigate these issues. However, a comprehensive comparison and benchmarking on an integrated platform with multiple data modalities with both perfect and defect materials data is still lacking. This work introduces JARVIS-Leaderboard, an open-source and community-driven platform that facilitates benchmarking and enhances reproducibility. The platform allows users to set up benchmarks with custom tasks and enables contributions in the form of dataset, code, and meta-data submissions. We cover the following materials design categories: Artificial Intelligence (AI), Electronic Structure (ES), Force-fields (FF), Quantum Computation (QC) and Experiments (EXP). For AI, we cover several types of input data, including atomic structures, atomistic images, spectra, and text. For ES, we consider multiple ES approaches, software packages, pseudopotentials, materials, and properties, comparing results to experiment. For FF, we compare multiple approaches for material property predictions. For QC, we benchmark Hamiltonian simulations using various quantum algorithms and circuits. Finally, for experiments, we use the inter-laboratory approach to establish benchmarks. There are 1281 contributions to 274 benchmarks using 152 methods with more than 8 million data-points, and the leaderboard is continuously expanding. The JARVIS-Leaderboard is available at the website: https://pages.nist.gov/jarvis_leaderboar

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain