DNA methylation contributes to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements. In this study, we use CRISPR-Cas9 technology to delete DNMT1, the DNA methyltransferase key for DNA methylation maintenance, in human neural progenitor cells (hNPCs). We observe that inactivation of DNMT1 in hNPCs results in viable, proliferating cells despi

Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and

Neuroanatomy suggests that adjacent neocortical neurons share a similar set of afferent synaptic inputs, as opposed to neurons localized to different areas of the neocortex. In the present study, we made simultaneous single-electrode patch clamp recordings from two or three adjacent neurons in the primary somatosensory cortex (S1) of the ketamine-xylazine anesthetized rat in vivo to study the corr

Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trai

This paper proposes a theory of gazelle growth in which gazelles can grow either organically or through acquisitions. The model includes three types of firms: incumbent, target, and gazelle. We show that the lower cost of organic growth can increase the incentives for acquisition growth because the incumbent understands that if it acquires the target firm, the gazelle will then invest organically

The need for energy in water provision and use is obvious, however the drivers are often complex, difficult to assess, and often inconsistently presented. Here we build a clearer definition and conceptual framework of “water-related energy”. We apply this framework to harmonise data and results across disparate studies so that regional estimates of water-related energy can be compared in a consist

Both numerical simulations and experiments were conducted in a heavy-duty DICI engine, with PRF81 as a gasoline surrogate, to investigate how the fuel stratification, auto-ignition and combustion are affected by the start of injection (SOI). The intake air temperature was adjusted to keep the combustion phasing constant when the SOI was swept from −100 to −20 oCA ATDC, covering different regimes o

In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPs). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of

Pathogens that invade the human host are confronted by a multitude of defence mechanisms aimed at preventing colonization, dissemination and proliferation. The most frequent outcome of this interaction is microbial elimination, in which the complement system plays a major role. Complement, an essential feature of the innate immune machinery, rapidly identifies and marks pathogens for efficient rem

Introduction: This study aimed to investigate the dose-response and pharmacology of a range of single doses of nebulised ensifentrine (RPL554), an inhaled dual phosphodiesterase (PDE) 3/4 inhibitor in patients with asthma. Methods: In this randomised, placebo-controlled, double-blind crossover study, patients received single nebulised doses of ensifentrine 0.4, 1.5, 6 and 24 mg, salbutamol 2.5 and

Super-Earths - planets with sizes between the Earth and Neptune - are found in tighter orbits than that of the Earth around more than one third of main sequence stars. It has been proposed that super-Earths are scaled-up terrestrial planets that also formed similarly, through mutual accretion of planetary embryos, but in discs much denser than the solar protoplanetary disc. We argue instead that t

We consider the problem of grid-forming control of power converters in low-inertia power systems. Starting from an average-switch three-phase power converter model, we draw parallels to a synchronous machine (SM) model and propose a novel converter control strategy which dwells upon the main characteristic of a SM: the presence of an internal rotating magnetic field. In particular, we augment the

We propose a novel control strategy for grid-forming converters in low-inertia power grids. Our strategy is inspired by identifying the structural similarities between the 3-phase DC/AC converter and the synchronous machine model. We explicitly match these models through modulation control so that they become structurally equivalent. Compared to standard emulation of virtual synchronous machines,

This paper formulates and addresses the problem of equivalence in terms of multistability properties between nonlinear models of gene regulatory systems of different dimensionality. Given a nonlinear dynamical model of a gene regulatory network and the structure of another higher-dimensional gene regulatory network, the aim is to find a dynamical model for the latter that has the same equilibria a

If experience is the guiding light in entrepreneurship education, then why is there so little mention of a philosophy of experience? This article aims to illuminate the philosophical foundations upon which entrepreneurship education rests by discussing learning through experience. In particular, we discuss the concept of experience used in educational research and learning activities for fostering

A search for high-mass dielectron and dimuon resonances in the mass range of 250 GeV to 6 TeV is presented. The data were recorded by the ATLAS experiment in proton–proton collisions at a centre-of-mass energy of s=13 TeV during Run 2 of the Large Hadron Collider and correspond to an integrated luminosity of 139 fb−1. A functional form is fitted to the dilepton invariant-mass distribution to model

The crystalline lens of the vertebrate eye grows throughout life. This growth may be enormous in fish, while the lens must be functional from larva to adult. During growth, the fiber cells of the lens must increase the concentration of specific proteins (crystallins) in the cytoplasm to increase refractive index. However, the bulk of the fiber cells in a vertebrate lens are denucleated and have no

Report for Tillväxtverket – the Swedish Agency for Economic and Regional Growth.