1,096 research outputs found
Stabilized high-power laser system for the gravitational wave detector advanced LIGO
An ultra-stable, high-power cw Nd:YAG laser system, developed for the ground-based gravitational wave detector Advanced LIGO (Laser Interferometer Gravitational-Wave Observatory), was comprehensively characterized. Laser power, frequency, beam pointing and beam quality were simultaneously stabilized using different active and passive schemes. The output beam, the performance of the stabilization, and the cross-coupling between different stabilization feedback control loops were characterized and found to fulfill most design requirements. The employed stabilization schemes and the achieved performance are of relevance to many high-precision optical experiments
Cryptotomography: reconstructing 3D Fourier intensities from randomly oriented single-shot diffraction patterns
We reconstructed the 3D Fourier intensity distribution of mono-disperse
prolate nano-particles using single-shot 2D coherent diffraction patterns
collected at DESY's FLASH facility when a bright, coherent, ultrafast X-ray
pulse intercepted individual particles of random, unmeasured orientations. This
first experimental demonstration of cryptotomography extended the
Expansion-Maximization-Compression (EMC) framework to accommodate unmeasured
fluctuations in photon fluence and loss of data due to saturation or background
scatter. This work is an important step towards realizing single-shot
diffraction imaging of single biomolecules.Comment: 4 pages, 4 figure
GEO 600 and the GEO-HF upgrade program: successes and challenges
The German-British laser-interferometric gravitational wave detector GEO 600
is in its 14th year of operation since its first lock in 2001. After GEO 600
participated in science runs with other first-generation detectors, a program
known as GEO-HF began in 2009. The goal was to improve the detector sensitivity
at high frequencies, around 1 kHz and above, with technologically advanced yet
minimally invasive upgrades. Simultaneously, the detector would record science
quality data in between commissioning activities. As of early 2014, all of the
planned upgrades have been carried out and sensitivity improvements of up to a
factor of four at the high-frequency end of the observation band have been
achieved. Besides science data collection, an experimental program is ongoing
with the goal to further improve the sensitivity and evaluate future detector
technologies. We summarize the results of the GEO-HF program to date and
discuss its successes and challenges
Virtual screening for inhibitors of the human TSLP:TSLPR interaction
The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation
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Aerosol sample preparation methods for X-ray diffractive imaging: Size-selected spherical nanoparticles on silicon nitride foils
Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production
NAD+ is both a co-enzyme for hydride transfer enzymes and a
substrate of sirtuins and other NAD+ consuming enzymes.
NAD+ biosynthesis is required for two different regimens
that extend lifespan in yeast. NAD+ is synthesized from
tryptophan and the three vitamin precursors of NAD+: nicotinic
acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells
with NAD+ precursors increases intracellular
NAD+ levels and extends replicative lifespan. Here we show
that both nicotinamide riboside and nicotinic acid are not only vitamins but are
also exported metabolites. We found that the deletion of the nicotinamide
riboside transporter, Nrt1, leads to increased export of nicotinamide riboside.
This discovery was exploited to engineer a strain to produce high levels of
extracellular nicotinamide riboside, which was recovered in purified form. We
further demonstrate that extracellular nicotinamide is readily converted to
extracellular nicotinic acid in a manner that requires intracellular
nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is
elevated by the deletion of the nicotinic acid transporter, Tna1. The data
indicate that NAD+ metabolism has a critical extracellular
element in the yeast system and suggest that cells regulate intracellular
NAD+ metabolism by balancing import and export of
NAD+ precursor vitamins
Microcondylaea bonellii as a new host for the European bitterling Rhodeus amarus
We report for the first time that the freshwater mussel Microcondylaea bonellii (Ferussac, 1827) functions as a suitable host for the European bitterling Rhodeus amarus (Bloch, 1782). Given the recent expansion of R. amarus in Europe, the possible physiological cost (e.g. competition for oxygen, reduction in water circulation, and consequent impairment of filter-feeding) of this interaction may further affect the already poor conservation status of M. bonellii populations.We acknowledge the two anonymous referees for the helpful suggestions that improve the clarity of our manuscript. This research was funded by FCT under project ConBiomics No NORTE-01-0145-FEDER-030286, cofinanced by COMPETE 2020, Portugal 2020 and the European Union through the ERDF
Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows
We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.Fil: Goncearenco, Alexander. National Institutes of Health; Estados UnidosFil: Li, Minghui. Soochow University; China. National Institutes of Health; Estados UnidosFil: Simonetti, Franco Lucio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones BioquĂmicas de Buenos Aires. FundaciĂłn Instituto Leloir. Instituto de Investigaciones BioquĂmicas de Buenos Aires; ArgentinaFil: Shoemaker, Benjamin A. National Institutes of Health; Estados UnidosFil: Panchenko, Anna R. National Institutes of Health; Estados Unido
In-situ observation of the formation of laser-induced periodic surface structures with extreme spatial and temporal resolution
Irradiation of solid surfaces with intense ultrashort laser pulses represents a unique way of depositing energy into materials. It allows to realize states of extreme electronic excitation and/or very high temperature and pressure, and to drive materials close to and beyond fundamental stability limits. As a consequence, structural changes and phase transitions often occur along unusual pathways and under strongly non-equilibrium conditions. Due to the inherent multiscale nature - both temporally and spatially - of these irreversible processes their direct experimental observation requires techniques that combine high temporal resolution with the appropriate spatial resolution and the capability to obtain good quality data on a single pulse/event basis. In this respect fourth generation light sources, namely short wavelength, short pulse free electron lasers (FELs) are offering new and fascinating possibilities. As an example, this chapter will discuss the results of scattering experiments carried at the FLASH free electron laser at DESY (Hamburg, Germany), which allowed us to resolve laser-induced structure formation at surfaces on the nanometer to sub-micron length scale and in temporal regimes ranging from picoseconds to several nanoseconds with sub-picosecond resolution
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