High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a nonpolar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard ­reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto ester derived and an α-phenyl cyclohexanone-­derived enol carbonate

A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B

A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B

Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides

Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing aryl bromides with electron-deficient secondary phosphine oxides is reported. The resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX ligands. The presented strategy is a useful alternative to known methods for constructing PHOX derivatives

DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity.

An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple ([Formula: see text]40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples

The wealth (disadvantage) of single-parent households

Wealth is a buffer against economic shocks and the intergenerational transmission of disadvantage. We investigate the wealth of single-parent households in six high-income countries that span a variety of institutional contexts and welfare regimes. Using household survey data, we show that single-parent households in all these countries are disadvantaged in the wealth they hold, compared to dual-parent households—more so in Great Britain, France, Germany, and the United States; and less so in Italy and, especially, Spain. We tease out major differences in types of wealth holdings in single- and dual-parent households. We find that the single-parent wealth deficit is not explained by differences in age or number of children but that it is influenced by education, income, homeownership, and receipt of intergenerational transfers. We discuss the policy implications of our findings, both in terms of how single parents are treated in social protection and taxation systems and, more broadly, in the supports they require if they are to overcome barriers to accumulating wealth

Intergenerational wealth transfers in Great Britain from the Wealth and Assets Survey in comparative perspective

Wealth surveys that collect information on intergenerational transfers provide new scope for comparative study of those transfers and their relationship with wealth across rich countries. However, this is problematic in the case of Great Britain, due to specific features of the Wealth and Assets Survey (WAS), the central source of survey-based household wealth data, in particular the extent of missing information in its first wave. This has severely constrained efforts to investigate patterns of wealth transfer in Great Britain in comparative perspective. In this paper, we set out these issues and present ways of dealing with them. On this basis, we then examine the main similarities and differences in patterns of intergenerational transmission of wealth between Great Britain, France, Germany, Italy, Spain and the United States. Our findings reveal common features across these countries as well as some important respects in which Great Britain was distinctive, though less of an outlier than the US. About 35 per cent of British households reported receiving an intergenerational wealth transfer at some point, similar to most of the comparator countries but much higher than the US. We conclude by setting out how WAS can be enhanced to address these issues at source, proposals with which the Office for National Statistics is seriously engaged