[Abstract unavailable

Making use of the osmotic pressure difference between fresh water and seawater is an attractive, renewable and clean way to generate power and is known as 'blue energy' 1-3 . Another electrokinetic phenomenon, called the streaming potential, occurs when an electrolyte is driven through narrow pores either by a pressure gradient 4 or by an osmotic potential resulting from a salt concentration gradient 5 . For this task, membranes made of two-dimensional materials are expected to be the most efficient, because water transport through a membrane scales inversely with membrane thickness 5-7 . Here we demonstrate the use of single-layer molybdenum disulfide (MoS 2 ) nanopores as osmotic nanopower generators. We observe a large, osmotically induced current produced from a salt gradient with an estimated power density of up to 10 6 watts per square metre-a current that can be attributed mainly to the atomically thin membrane of MoS 2 . Low power requirements for nanoelectronic and optoelectric devices can be provided by a neighbouring nanogenerator that harvests energy from the local environment 8-11 -for example, a piezoelectric zinc oxide nanowire array 8 or single-layer MoS 2 (ref. 12). We use our MoS 2 nanopore generator to power a MoS 2 transistor, thus demonstrating a self-powered nanosystem.MoS 2 nanopores have already demonstrated better water-transport behaviour than graphene 13,14 owing to the enriched hydrophilic surface sites (provided by the molybdenum) that are produced following either irradiation with transmission electron microscopy (TEM) 15 or electrochemical oxidation 16 . The osmotic power is generated by separating two reservoirs containing potassium chloride (KCl) solutions of different concentrations with a freestanding MoS 2 membrane, into which a single nanopore has been introduced 13 . A chemical potential gradient arises at the interface of these two liquids at a nanopore in a 0.65-nm-thick, single-layer MoS 2 membrane, and drives ions spontaneously across the nanopore, forming an osmotic ion flux towards the equilibrium state (Fig. 1a). The presence of surface charges on the pore screens the passing ions according to their charge polarity, and thus results in a net measurable osmotic current, known as reverse electrodialysis 1 . This cation selectivity can be better understood by analysing the concentration of each ion type (potassium and chloride) as a function of the radial distance from the centre of the pore, as we show here through molecular-dynamics simulations (Fig. 1b).We fabricated MoS 2 nanopores either by TEM 13 (Fig. 1c) Distance from the centre of the pore (Å)C max /C min = 1,000C max /C min = 500C max /C min = 100 LETTER RESEARCHosmotic current can be expected, owing to the long time required for the system to reach equilibrium. We measured the osmotic current and voltage across the pore by using a pair of Ag/AgCl electrodes to characterize the current-voltage (I-V) response of the nanopore.To gain a better insight into the performance of the MoS 2 nanopore power generator, ...

Summary The high rate of clinical response to protein kinase-targeting drugs matched to cancer patients with specific genomic alterations has prompted efforts to use cancer cell-line (CCL) profiling to identify additional biomarkers of small-molecule sensitivities. We have quantitatively measured the sensitivity of 242 genomically characterized CCLs to an Informer Set of 354 small molecules that target many nodes in cell circuitry, uncovering protein dependencies that: 1) associate with specific cancer-genomic alterations and 2) can be targeted by small molecules. We have created the Cancer Therapeutics Response Portal (www.broadinstitute.org/ctrp) to enable users to correlate genetic features to sensitivity in individual lineages and control for confounding factors of CCL profiling. We report a candidate dependency, associating activating mutations in the oncogene β-catenin with sensitivity to the Bcl2-family antagonist, navitoclax. The resource can be used to develop novel therapeutic hypotheses and accelerate discovery of drugs matched to patients by their cancer genotype and lineage.

N(6)-methyladenosine (m(6)A) is the most abundant internal modification of nearly all eukaryotic mRNAs and has recently been reported to be recognized by the YTH domain family proteins. Here we present the crystal structures of the YTH domain of YTHDC1, a member of the YTH domain family, and its complex with an m(6)A-containing RNA. Our structural studies, together with transcriptome-wide identification of YTHDC1-binding sites and biochemical experiments, not only reveal the specific mode of m(6)A-YTH binding but also explain the preferential recognition of the GG(m(6)A)C sequences by YTHDC1.