We develop a theoretical definition of operational capabilities, based on the strategic management and operations management literature, and differentiate this construct from the related constructs of resources and operational practices, drawing upon the resourcebased view of the firm as our foundation. We illustrate the key features of operational capabilities using the illustration of a restaurant kitchen. Because the traits of operational capabilities are distinct, they create a barrier to imitation, making them a potential source of competitive advantage. However, operational capabilities are particularly challenging to measure, because they emerge gradually and are tacit, embedded, and manifested differently across firms. In solving this measurement conundrum, we draw upon similar situations experienced by Schein (2004) and Eisenhardt and Martin (2000) in operationalizing organizational culture and dynamic capabilities. A taxonomy of six emergent operational capabilities is developed: operational improvement, operational innovation, operational customization, operational cooperation, operational responsiveness, and operational reconfiguration. A set of measurement scales is developed, in order to measure each of the operational capabilities, and validated using two different datasets. This allows replication of the psychometric properties of the multi-item scales and helps to ensure the validity of the resulting measures.

Large-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biological systems. However, no current techniques enable optical imaging of uniquely-tagged individual cells. Fluorescence-based approaches can only distinguish a small number of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we investigate large-scale cell tracking using intracellular laser particles as imaging probes that emit coherent laser light with a characteristic wavelength. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1170 to 1580 nm with sub-nm linewidths, enabling massive spectral Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Super-enhancers are large clusters of enhancers that activate gene expression. Broad trimethyl histone H3 lysine 4 (H3K4me3) often defines active tumor suppressor genes. However, how these epigenomic signatures are regulated for tumor suppression is little understood. Here we show that brain-specific knockout of the H3K4 methyltransferase MLL4 (a COMPASS-like enzyme, also known as KMT2D) in mice spontaneously induces medulloblastoma. Mll4 loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. MLL4 enhances DNMT3A-catalyzed DNA methylation and SIRT1/BCL6-mediated H4K16 deacetylation, which antagonize expression of Ras activators and Notch pathway components, respectively. Notably, Mll4 loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6) by diminishing broad H3K4me3 and super-enhancers and also causes widespread impairment of these epigenomic signatures during medulloblastoma genesis. These findings suggest an anti-tumor role for super-enhancers and provide a unique tumor-suppressive mechanism in which MLL4 is necessary to maintain broad H3K4me3 and super-enhancers at tumor suppressor genes.

The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug–polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.