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The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy. Significance Tumor cells are heterogeneous, and much variation occurs at the single-cell level, which may contribute to therapeutic response. Here, we studied drug resistance dynamics in a model of tolerance with a metastatic breast cancer cell line by leveraging the power of single-cell RNA-Seq technology. Drug-tolerant cells within a single clone rapidly express high cell-to-cell transcript variability, with a gene expression profile similar to untreated cells, and the population reacquires paclitaxel sensitivity. Our gene expression and single nucleotide variants analyses suggest that equivalent phenotypes are achieved without relying on a unique molecular event or fixed transcriptional programs. Thus, transcriptional heterogeneity might ensure survival of cancer cells with equivalent combinations of gene expression programs and/or single nucleotide variants.

We study how monetary policy affects the funding composition of the banking sector. When monetary tightening reduces the supply of retail deposits, banks attempt to substitute wholesale funding for deposit outflows to smooth their lending. Because of financial frictions, banks have varying degrees of access to wholesale funding. Therefore, large banks, or those with greater reliance on wholesale funding, increase their wholesale funding more. Consequently, monetary tightening increases both the reliance on and the concentration of wholesale funding within the banking sector. Our findings also suggest that liquidity requirements could bolster monetary policy transmission through the bank lending channel. This paper was accepted by Tyler Shumway, finance .

Mast cells are tissue-resident cells playing major roles in homeostasis and disease conditions. Lung mast cells are particularly important in airway inflammatory diseases such as asthma. Human mast cells are classically divided into the subsets MC T and MC TC , where MC T express the mast cell protease tryptase and MC TC in addition express chymase, carboxypeptidase A3 (CPA3) and cathepsin G. Apart from the disctintion of the MC T and MC TC subsets, little is known about the heterogeniety of human lung mast cells and a deep analysis of their heterogeniety has previously not been performed. We therefore performed single cell RNA sequencing on sorted human lung mast cells using SmartSeq2. The mast cells showed high expression of classical mast cell markers. The expression of several individual genes varied considerably among the cells, however, no subpopulations were detected by unbiased clustering. Variable genes included the protease-encoding transcripts CMA1 (chymase) and CTSG (cathepsin G). Human lung mast cells are predominantly of the MC T subset and consistent with this, the expression of CMA1 was only detectable in a small proportion of the cells, and correlated moderately to CTSG . However, in contrast to established data for the protein, CPA3 mRNA was high in all cells and the correlation of CPA3 to CMA1 was weak.

The purpose of this essay is to discuss key issues and research needs in deep hydrogeology. It is based on a workshop on the subject held at Uppsala University in Sweden, with participants from 11 countries, including the USA, Russia, Japan and a number of European countries (Tsang et al. 2012). The following discussion will be divided into sections on permeability structures, driving forces, coupled processes, borehole testing and data analysis, followed by a few concluding remarks.

We study how market structure within a product category varies across retail formats. Building on the literature on internal market structure, we estimate a joint store and brand choice model where the loading matrix of brand attributes are allowed to be retail format specific. The approach allows us to recover brand maps for different retail formats while controlling for the short-term marketing mix activities at these stores and the self-selection of households that frequent a particular format. The model is applied to consumer panel data from two product categories, where households are observed to make purchases across three store types: high-end grocery store, traditional supermarket, and large everyday low pricing (EDLP) formats. Our results show strong correlations between the marketing mix sensitivities, store format preference, and unobserved brand attributes. These correlations translate into significant differences in market structure across retail formats and in the direction and size of preference vectors for unobservable brand attributes. We find a tight clustering of brands at the EDLP format, whereas brands are found to compete in distinct subgroups at other stores. Results show that failure to account for retail format effects can substantially bias the understanding of underlying market structure and could lead to incorrect implications in applications such as new product entry.

Este trabajo evalúa el impacto del envío del anexo de proyección de pensiones personalizada (PPP), que muestra el retorno de postergar la jubilación 3 años después de la edad legal, sobre la decisión de jubilación de los afiliados al sistema de pensiones chileno. Se utiliza una metodología cuasiexperimental de evaluación de programas que busca corregir por la endogeneidad del tratamiento, usando como instrumentos información geográfica, demográfica y de número de oficinas de correos por región. Los resultados muestran que recibir la PPP en una ocasión no tiene efectos significativos sobre la decisión de jubilación. No obstante, cuando se toma en cuenta la intensidad del tratamiento, se encuentra que haber recibido la PPP en dos años consecutivos, 2005 y 2006, reduce significativamente la probabilidad de jubilar el año 2011. Por último, los resultados muestran que el efecto del tratamiento es mayor en individuos de mayor ahorro obligatorio.