Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1

Time series aggregation, disaggregation and long memory

We study the aggregation/disaggregation problem of random parameter AR(1) processes and its relation to the long memory phenomenon. We give a characterization of a subclass of aggregated processes which can be obtained from simpler, "elementary", cases. In particular cases of the mixture densities, the structure (moving average representation) of the aggregated process is investigated

Feedback-Optimized Operations with Linear Ion Crystals

We report on transport operations with linear crystals of 40Ca+ ions by applying complex electric time-dependent potentials. For their control we use the information obtained from the ions' fluorescence. We demonstrate that by means of this feedback technique, we can transport a predefined number of ions and also split and unify ion crystals. The feedback control allows for a robust scheme, compensating for experimental errors as it does not rely on a precisely known electrical modeling of the electric potentials in the ion trap beforehand. Our method allows us to generate a self-learning voltage ramp for the required process. With an experimental demonstration of a transport with more than 99.8 % success probability, this technique may facilitate the operation of a future ion based quantum processor

Advancing atomic nanolithography: cold atomic Cs beam exposure of alkanethiol self-assembled monolayers

We report the results of a study into the quality of functionalized surfaces for nanolithographic imaging. Self-assembled monolayer (SAM) coverage, subsequent post-etch pattern definition and minimum feature size all depend on the quality of the Au substrate used in atomic nanolithographic experiments. We find sputtered Au substrates yield much smoother surfaces and a higher density of {111} oriented grains than evaporated Au surfaces. A detailed study of the self-assembly mechanism using molecular resolution AFM and STM has shown that the monolayer is composed of domains with sizes typically of 5-25 nm, and multiple molecular domains can exist within one Au grain. Exposure of the SAM to an optically-cooled atomic Cs beam traversing a two-dimensional array of submicron material masks ans also standing wave optical masks allowed determination of the minimum average Cs dose (2 Cs atoms per SAM molecule) and the realization of < 50 nm structures. The SAM monolayer contains many non-uniformities such as pin-holes, domain boundaries and monoatomic depressions which are present in the Au surface prior to SAM adsorption. These imperfections limit the use of alkanethiols as a resist in atomic nanolithography experiments. These studies have allowed us to realize an Atom Pencil suitable for deposition of precision quantities of material at the microand nanoscale to an active surface

Coherent coupling of two quantum dots embedded in an Aharonov-Bohm ring

We define two laterally gated small quantum dots (~ 15 electrons) in an Aharonov-Bohm geometry in which the coupling between the two dots can be broadly changed. For weakly coupled quantum dots we find Aharonov-Bohm oscillations. In an intermediate coupling regime we concentrate on the molecular states of the double dot and extract the magnetic field dependence of the coherent coupling.Comment: 6 pages, 4 figure

Effect of Influenza Vaccination on Viral Replication and Immune Response in Persons Infected with Human Immunodeficiency Virus Receiving Potent Antiretroviral Therapy

Nineteen patients infected with human immunodeficiency virus (HIV) with varying levels of viral suppression achieved with antiretroviral therapy were evaluated to determine whether trivalent influenza vaccine activated HIV replication. Humoral immune responses and CD4+ lymphocyte subsets were compared in 5 HIV-uninfected vaccinated subjects. Transient elevations of plasma HIV RNA levels (76-89 copies/mL) appeared within 2 weeks in 3 of 11 patients with 50 copies/mL. HIV DNA decreased in patients with <400 RNA copies/mL at baseline and showed an HIV RNA increase after vaccination (n = 8) when compared with 8 patients with <50 copies/mL at baseline who lacked viral response to vaccination. Concurrent decreases in proviral DNA and memory phenotype CD4+ cells in association with increased plasma HIV RNA after vaccination in patients with <400 RNA copies/mL at baseline suggest that in vivo mobilization of the latently infected cell reservoir may occur during potent antiretroviral therap

The atom pencil: serial writing in the sub-micrometre domain

The atom pencil we describe here is a versatile tool that writes arbitrary structures by atomic deposition in a serial lithographic process. This device consists of a transversely laser-cooled and collimated cesium atomic beam that passes through a 4-pole atom-flux concentrator and impinges on to micron- and sub-micron-sized apertures. The aperture translates above a fixed substrate and enables the writing of sharp features with sizes down to 280 nm. We have investigated the writing and clogging properties of an atom pencil tip fabricated from silicon oxide pyramids perforated at the tip apex with a sub-micron aperture

Widely tunable laser frequency offset lock with 30 GHz range and 5 THz offset

We demonstrate a simple and versatile method to greatly extend the tuning range of optical frequency shifting devices, such as acousto-optic modulators (AOMs). We use this method to stabilize the frequency of a tunable narrow-band continuous-wave (CW) laser to a transmission maximum of an external Fabry-Perot interferometer (FPI) with a tunable frequency offset. This is achieved through a servo loop which contains an in-loop AOM for simple radiofrequency (RF) tuning of the optical frequency over the full 30 GHz mode-hop-free tuning range of the CW laser. By stabilizing the length of the FPI to a stabilized helium-neon (HeNe) laser (at 5 THz offset from the tunable laser) we simultaneously transfer the similar to 1 MHz absolute frequency stability of the HeNe laser to the entire 30 GHz range of the tunable laser. Thus, our method allows simple, wide-range, fast and reproducible optical frequency tuning and absolute optical frequency measurements through RF electronics, which is here demonstrated by repeatedly recording a 27-GHz-wide molecular iodine spectrum at scan rates up to 500 MHz/s. General technical aspects that determine the performance of the method are discussed in detail. (C) 2013 Optical Society of Americ

An assessment of subsurface residual stresses analysis in SLM Ti 6Al 4V

Ti-6Al-4V bridges were additively fabricated by selective laser melting (SLM) under different scanning speed conditions, to compare the effect of process energy density on the residual stress state. Subsurface lattice strain characterization was conducted by means of synchrotron diffraction in energy dispersive mode. High tensile strain gradients were found at the frontal surface for samples in an as-built condition. The geometry of the samples promotes increasing strains towards the pillar of the bridges. We observed that the higher the laser energy density during fabrication, the lower the lattice strains. A relief of lattice strains takes place after heat treatment

Mid-ocean microseisms

Author Posting. © American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 6 (2005): Q04009, doi:10.1029/2004GC000768.The Hawaii-2 Observatory (H2O) is an excellent site for studying the source regions and propagation of microseisms since it is located far from shorelines and shallow water. During Leg 200 of the Ocean Drilling Program, the officers of the JOIDES Resolution took wind and wave measurements for comparison with double-frequency (DF) microseism data collected at nearby H2O. The DF microseism band can be divided into short period and long period bands, SPDF and LPDF, respectively. Comparison of the ship’s weather log with the seismic data in the SPDF band from about 0.20 to 0.45 Hz shows a strong correlation of seismic amplitude with wind speed and direction, implying that the energy reaching the ocean floor is generated locally by ocean gravity waves. Near-shore land seismic stations see similar SPDF spectra, also generated locally by wind seas. At H2O, SPDF microseism amplitudes lag sustained changes in wind speed and direction by several hours, with the lag increasing with wave period. This lag may be associated with the time necessary for the development of opposing seas for DF microseism generation. Correlation of swell height above H2O with the LPDF band from 0.085 to 0.20 Hz is often poor, implying that a significant portion of this energy originates at distant locations. Correlation of the H2O seismic data with NOAA buoy data, with hindcast wave height data from the North Pacific, and with seismic data from mainland and island stations, defines likely source areas of the LPDF signals. Most of the LPDF energy at H2O appears to be generated by high amplitude storm waves impacting long stretches of coastline nearly simultaneously, and the Hawaiian Islands appear to be a significant source of LPDF energy in the North Pacific when waves arrive from particular directions. The highest DF levels observed at mid-ocean site H2O occur in the SPDF band when two coincident nearby storm systems develop. Mid-ocean generated DF microseisms are not observed at interior continental sites, indicating high attenuation of these signals. At near-coastal seismic stations, both SPDF and LPDF microseism levels are generally dominated by local generation at nearby shorelines.This work was supported by the U.S. Science Support Program (User Reference: 418920-BA372; Task Order F001602) associated with the Ocean Drilling Program and is sponsored by the National Science Foundation and the Joint Oceanographic Institutions, Inc. Additional support was provided by the California Energy Commission and the California Department of Boating and Waterways as part of their program to improve boating facilities, access, safety, and education. Support for Ralph Stephen was also provided by the National Science Foundation under Grant #OCE-0424633