Atomic inner-shell X-ray laser at 1.46 nanometres pumped by an X-ray free-electron laser

Since the invention of the laser more than 50 years ago, scientists have striven to achieve amplification on atomic transitions of increasingly shorter wavelength. The introduction of X-ray free-electron lasers makes it possible to pump new atomic X-ray lasers with ultrashort pulse duration, extreme spectral brightness and full temporal coherence. Here we describe the implementation of an X-ray laser in the kiloelectronvolt energy regime, based on atomic population inversion and driven by rapid K-shell photo-ionization using pulses from an X-ray free-electron laser. We established a population inversion of the Kα transition in singly ionized neon at 1.46 nanometres (corresponding to a photon energy of 849 electronvolts) in an elongated plasma column created by irradiation of a gas medium. We observed strong amplified spontaneous emission from the end of the excited plasma. This resulted in femtosecond-duration, high-intensity X-ray pulses of much shorter wavelength and greater brilliance than achieved with previous atomic X-ray lasers. Moreover, this scheme provides greatly increased wavelength stability, monochromaticity and improved temporal coherence by comparison with present-day X-ray free-electron lasers. The atomic X-ray lasers realized here may be useful for high-resolution spectroscopy and nonlinear X-ray studies.     

Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5+ stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5+ stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.     

Heterogeneous pathways and timing of factor departure during translation initiation

The initiation of translation establishes the reading frame for protein synthesis and is a key point of regulation. Initiation involves factor-driven assembly at a start codon of a messenger RNA of an elongation-competent 70S ribosomal particle (in bacteria) from separated 30S and 50S subunits and initiator transfer RNA. Here we establish in Escherichia coli, using direct single-molecule tracking, the timing of initiator tRNA, initiation factor 2 (IF2; encoded by infB) and 50S subunit joining during initiation. Our results show multiple pathways to initiation, with orders of arrival of tRNA and IF2 dependent on factor concentration and composition. IF2 accelerates 50S subunit joining and stabilizes the assembled 70S complex. Transition to elongation is gated by the departure of IF2 after GTP hydrolysis, allowing efficient arrival of elongator tRNAs to the second codon presented in the aminoacyl-tRNA binding site (A site). These experiments highlight the power of single-molecule approaches to delineate mechanisms in complex multicomponent systems.     

Design of Magnetic RF Inductor in CMOS

Traditional planar inductors in Radio Frequency (RF) Integrated Circuits (ICs) are plagued by large areas, low quality, and low frequencies. This paper describes a magnetic-based CMOS-compatible RF in-ductor. Magnetic-core inductors with various ferrite-filled structures, spiral structures, and magnetic material permeabilities were simulated to show that this inductor greatly improves the inductance by up to 97% and quality factor by 18.6% over a multi-GHz frequency range. The results indicate that the inductor is a very promising and viable solution to realize miniature, high quality, and high frequency on-chip inductors for high-end RF ICs.     

A history of the axiomatic formulation of probability from Borel to Kolmogorov: Part I

This paper, the first of two, traces the origins of the modern axiomatic formulation of Probability Theory, which was first given in definitive form by Kolmogorov in 1933. Even before that time, however, a sequence of developments, initiated by a landmark paper of E. Borel, were giving rise to problems, theorems, and reformulations that increasingly related probability to measure theory and, in particular, clarified the key role of countable additivity in Probability Theory.This paper describes the developments from Borel's work through F. Hausdorff's. The major accomplishments of the period were Borel's Zero-One Law (also known as the Borel-Cantelli Lemmas), his Strong Law of Large Numbers, and his Continued Fraction Theorem. What is new is a detailed analysis of Borel's original proofs, from which we try to account for the roots (psychological as well as mathematical) of the many flaws and inadequacies in Borel's reasoning. We also document the increasing realization of the link between the theories of measure and of probability in the period from G. Faber to F. Hausdorff. We indicate the misleading emphasis given to independence as a basic concept by Borel and his equally unfortunate association of a Heine-Borel lemma with countable additivity. Also original is the (possible) genesis we propose for each of the two examples chosen by Borel to exhibit his new theory; in each case we cite a now neglected precursor of Borel, one of them surely known to Borel, the other, probably so. The brief sketch of instances of the Cantelli lemma before Cantelli's publication is also original.We describe the interesting polemic between F. Bernstein and Borel concerning the Continued Fraction Theorem, which serves as a rare instance of a contemporary criticism of Borel's reasoning. We also discuss Hausdorff's proof of Borel's Strong Law (which seems to be the first valid proof of the theorem along the lines sketched by Borel).In retrospect, one may ask why problems of geometric (or continuous) probability did not give rise to the (Kolmogorov) view of probability as a form of measure, rather than the study of repeated independent trials, which was Borel's approach. This paper shows that questions of geometric probability were always the essential guide to the early development of the theory, despite the contrary viewpoint exhibited by Borel's preferred interpretation of his own results.     

The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus)

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties.     

NLRX1 is a regulator of mitochondrial antiviral immunity

The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus-induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen-associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.