Concise Synthesis of a Pateamine A Analogue with In Vivo Anticancer Activity Based on an Iron-Catalyzed Pyrone Ring Opening/Cross-Coupling

The marine macrolide pateamine A and its non-natural sibling DMDA-Pat A are potent translation inhibitors targeting the eukaryotic initiation factor 4A (eIF4A), an enzyme with RNA helicase activity. Although essential for every living cell, this protein target seems “drugable” since DMDA-Pat A has previously been shown to exhibit remarkable in vivo activity against two different melanoma mouse models. The novel entry into this promising compound presented herein is shorter and significantly more productive than the literature route. Key to success was the masking of the signature Z,E-configured dienoate subunit of DMDA-Pat A in the form of a 2-pyrone ring, which was best crafted by a gold-catalyzed cyclization. While the robustness of the heterocycle facilitated the entire assembly stage, the highly isomerization-prone seco-Z,E-dienoic acid could be unlocked in due time for macrolactonization by an unconventional iron-catalyzed ring opening/cross coupling. Moreover, the crystal structure analysis of an advanced intermediate gave first insights into the conformation of the macrodilactone framework of the pateamine family, which is thought to be critical for eliciting the desired biological response

Forecasting Housing Prices under Different Submarket Assumptions

This research evaluated forecasting accuracy of hedonic price models based on a number of different submarket assumptions. Using home sale data for the City of Knoxville and vicinities merged with geographic information, we found that forecasting housing prices with submarkets defined using expert knowledge and by school district and combining information conveyed in different modeling strategies are more accurate and efficient than models that are spatially aggregated, or with submarkets defined by statistical clustering techniques. This finding provided useful implications for housing price prediction in an urban setting and surrounding areas in that forecasting models based on expert knowledge of market structure or public school quality and simple model combining techniques may outperform the models using more sophisticated statistical techniques.Clustering, Forecasting, Hedonic price, Housing Submarket, Demand and Price Analysis, C53, R21,

Generation of 3-Dimensional graph state with Josephson charge qubits

On the basis of generations of 1-dimensional and 2-dimensional graph states, we generate a 3-dimensional N3-qubit graph state based on the Josephson charge qubits. Since any two charge qubits can be selectively and effectively coupled by a common inductance, the controlled phase transform between any two-qubit can be performed. Accordingly, we can generate arbitrary multi-qubit graph states corresponding to arbitrary shape graph, which meet the expectations of various quantum information processing schemes. All the devices in the scheme are well within the current technology. It is a simple, scalable and feasible scheme for the generation of various graph states based on the Josephson charge qubits.Comment: 4 pages, 4 figure

Comparison of Proxy and Multimodel Ensemble Means

Proxy‐model comparisons show large discrepancies in the impact of volcanic aerosols on the hydrology of the Asian monsoon region (AMR). This was mostly imputed to uncertainties arising from the use of a single model in previous studies. Here we compare two groups of CMIP5 multimodel ensemble mean (MMEM) with the tree‐ring‐based reconstruction Monsoon Asia Drought Atlas (MADA PDSI), to examine their reliability in reproducing the hydrological effects of the volcanic eruptions in 1300–1850 CE. Time series plots indicate that the MADA PDSI and the MMEMs agree on the significant drying effect of volcanic perturbation over the monsoon‐dominated subregion, while disparities exist over the westerlies‐dominated subregion. Comparisons of the spatial patterns suggest that the MADA PDSI and the MMEMs show better agreement 1 year after the volcanic eruption than in the eruption year and in subregions where more tree‐ring chronologies are available. The MADA PDSI and the CMIP5 MMEMs agree on the drying effect of volcanic eruptions in western‐East Asia, South Asian summer monsoon, and northern East Asian summer monsoon (EASM) regions. Model results suggest significant wetting effect in southern EASM and western‐South Asia, which agrees with the observed hydrological response to the 1991 Mount Pinatubo eruption. Analysis on model output from the Last Millennium Ensemble project shows similar hydrological responses. These results suggest that the CMIP5 MMEM is able to reproduce the impact of volcanic eruptions on the hydrology of the southern AMR