298 research outputs found

    TLR4 activation induces IL-1ss release via an IPAF dependent but caspase 1/11/8 independent pathway in the lung

    Get PDF
    Background: The IL-1 family of cytokines is known to play an important role in inflammation therefore understanding the mechanism by which they are produced is paramount. Despite the recent plethora of publications dedicated to the study of these cytokines, the mechanism by which they are produced in the airway following endotoxin, Lipopolysaccharide (LPS), exposure is currently unclear. The aim was to determine the mechanism by which the IL-1 cytokines are produced after LPS inhaled challenge. Methods:Mice were challenged with aerosolised LPS, and lung tissue and bronchiolar lavage fluid (BALF) collected. Targets were measured at the mRNA and protein level; caspase activity was determined using specific assays. Results: BALF IL-1b/IL-18, but not IL-1a, was dependent on Ice Protease-Activating Factor (IPAF), and to a lesser extent Apoptosis-associated Speck-like protein containing a CARD (ASC). Interestingly, although we measured an increase in mRNA expression for caspase 1 and 11, we could not detect an increase in lung enzyme activity or a role for them in IL-1a/b production. Further investigations showed that whilst we could detect an increase in caspase 8 activity at later points in the time course (during resolution of inflammation), it appeared to play no role in the production of IL-1 cytokines in this model system. Conclusions: TLR4 activation increases levels of BALF IL-1b/IL-18 via an IPAF dependent and caspase 1/11/8 independent pathway. Furthermore, it would appear that the presence of IL-1a in the BALF is independent of these pathways. This novel data sheds light on innate signalling pathways in the lung that control the production of these key inflammatory cytokines

    Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema

    Get PDF
    Hyperpolarized 83Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate to surface to volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method utilizes the nuclear electric properties of the spin I = 9/2 isotope 83Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase induced model of emphysema. A significant 83Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase treated lungs compared to the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface to volume ratio in the emphysema model that was validated by histology. The finding supports usage of 83Kr SQUARE as new biomarker for surface to volume ratio changes in emphysema

    Multiple Stellar Fly-Bys Sculpting the Circumstellar Architecture in RW Aurigae

    Get PDF
    We present high-resolution ALMA Band 6 and 7 observations of the tidally disrupted protoplanetary disks of the RW Aurigae binary. Our observations reveal the presence of additional tidal streams to the previously observed tidal arm around RW Aur A. The observed configuration of tidal streams surrounding RW Aur A and B is incompatible with a single star--disk tidal encounter, suggesting that the RW Aurigae system has undergone multiple fly-by interactions. We also resolve the circumstellar disks around RW Aur A and B, with CO radii of 58 au and 38 au consistent with tidal truncation, and 2.5 times smaller dust emission radii. The disks appear misaligned by 12^{\circ} or 57^{\circ}. Using new photometric observations from the American Association of Variable Star Observers (AAVSO) and All Sky Automated Survey for SuperNovae (ASAS-SN) archives, we have also identified an additional dimming event of the primary that began in late 2017 and is currently ongoing. With over a century of photometric observations, we are beginning to explore the same spatial scales as ALMA

    Monocoque structure for the SKITTER three-legged walker

    Get PDF
    The SKITTER 2 design is a monocoque version of the proposed lunar three-legged walker. By the definition of monocoque, the body and legs are a shell with no internal ribbing or supports added for absorbing stresses. The purpose of the monocoque is to encase the elements used for power transmission, power supply, and control of the motion. The material for the structure is a vinyl ester resin, Derakane 8084. This material is easily formable and locally obtainable. The body consists of a hexagonally shaped cylinder with truncated hexagonal pyramids on the top and botton. The legs are eight inch diameter cylinders. The legs are comprised of a tibia section and a femur section. The SKITTER 2 is powered by six actuators which provide linear forces that are transformed into rotary torques by a series of chains and sprockets. The joints connect the femur to the body and the tibia to the femur. Surrounding the joints are flexible rubber hoses that fully encase the chains and sprockets. The SKITTER 2 is capable of walking upside down, righting itself after being overturned, and has the ability to perform in many environments. Applications for this walker include lunar transport or drilling, undersea exploration, and operation in severe surroundings such as arctic temperatures or high radiation

    From Geometry to Numerics: interdisciplinary aspects in mathematical and numerical relativity

    Full text link
    This article reviews some aspects in the current relationship between mathematical and numerical General Relativity. Focus is placed on the description of isolated systems, with a particular emphasis on recent developments in the study of black holes. Ideas concerning asymptotic flatness, the initial value problem, the constraint equations, evolution formalisms, geometric inequalities and quasi-local black hole horizons are discussed on the light of the interaction between numerical and mathematical relativists.Comment: Topical review commissioned by Classical and Quantum Gravity. Discussion inspired by the workshop "From Geometry to Numerics" (Paris, 20-24 November, 2006), part of the "General Relativity Trimester" at the Institut Henri Poincare (Fall 2006). Comments and references added. Typos corrected. Submitted to Classical and Quantum Gravit

    Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America

    Get PDF
    Climate warming is projected to affect forest water yields but the effects are expected to vary. We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm periods. Using the theoretical framework of the Budyko curve, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation (d) was defined as a catchment’s change in actual ET divided by P [AET/P; evaporative index (EI)] coincident with a shift from a cool to a warm period – a positive d indicates an upward shift in EI and smaller than expected water yields, and a negative d indicates a downward shift in EI and larger than expected water yields. Elasticity was defined as the ratio of inter annual variation in potential ET divided by P (PET/P; dryness index) to inter annual variation in the EI – high elasticity indicates low d despite large range in drying index (i.e., resilient water yields), low elasticity indicates high d despite small range in drying index (i.e., non-resilient water yields). Although the data needed to fully evaluate ecosystems based on these metrics are limited, we were able to identify some characteristics of response among forest types. Alpine sites showed the greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer forests included catchments with lowest elasticity and stable to larger water yields. Deciduous forests included catchments with intermediate elasticity and stable to smaller water yields. Mixed coniferous/deciduous forests included catchments with highest elasticity and stable water yields. Forest type appeared to influence the resilience of catchment water yields to climate warming, with conifer and deciduous catchments more susceptible to climate warming than the more diverse mixed forest catchments

    The Effect of Adult Aggression on Habitat Selection by Settlers of Two Coral-Dwelling Damselfishes

    Get PDF
    Coral-reef fishes experience a major challenge when facing settlement in a multi-threat environment, within which, using settlement cues, they need to select a suitable site. Studies in laboratories and artificial setups have shown that the presence of conspecific adults often serves as a positive settlement cue, whose value is explained by the increased survival of juveniles in an already proven fit environment. However, settlement in already inhabited corals may expose the recruits to adult aggression. Daily observations and manipulation experiments were used in the present study, which was conducted in the natural reef. We revealed differential strategies of settlers, which do not necessarily join conspecific adults. Dascyllus aruanus prefer to settle near (not with) their aggressive adults, and to join them only after gaining in size; whereas Dascyllus marginatus settlers in densely populated reefs settle independently of their adult distribution. Our results present different solutions to the challenges faced by fish recruits while selecting their microhabitat, and emphasize the complexity of habitat selection by the naïve settlers. Although laboratory experiments are important to the understanding of fish habitat selection, further studies in natural habitats are essential in order to elucidate the actual patterns of settlement and habitat selection, which are crucial for the survival of coral-reef fish populations

    LSST: from Science Drivers to Reference Design and Anticipated Data Products

    Get PDF
    (Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2^2 field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5σ\sigma point-source depth in a single visit in rr will be 24.5\sim 24.5 (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg2^2 with δ<+34.5\delta<+34.5^\circ, and will be imaged multiple times in six bands, ugrizyugrizy, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg2^2 region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to r27.5r\sim27.5. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

    A Methodological Framework for the Reconstruction of Contiguous Regions of Ancestral Genomes and Its Application to Mammalian Genomes

    Get PDF
    The reconstruction of ancestral genome architectures and gene orders from homologies between extant species is a long-standing problem, considered by both cytogeneticists and bioinformaticians. A comparison of the two approaches was recently investigated and discussed in a series of papers, sometimes with diverging points of view regarding the performance of these two approaches. We describe a general methodological framework for reconstructing ancestral genome segments from conserved syntenies in extant genomes. We show that this problem, from a computational point of view, is naturally related to physical mapping of chromosomes and benefits from using combinatorial tools developed in this scope. We develop this framework into a new reconstruction method considering conserved gene clusters with similar gene content, mimicking principles used in most cytogenetic studies, although on a different kind of data. We implement and apply it to datasets of mammalian genomes. We perform intensive theoretical and experimental comparisons with other bioinformatics methods for ancestral genome segments reconstruction. We show that the method that we propose is stable and reliable: it gives convergent results using several kinds of data at different levels of resolution, and all predicted ancestral regions are well supported. The results come eventually very close to cytogenetics studies. It suggests that the comparison of methods for ancestral genome reconstruction should include the algorithmic aspects of the methods as well as the disciplinary differences in data aquisition

    Social Networking Technology, Social Network Composition, and Reductions in Substance Use Among Homeless Adolescents

    Get PDF
    Peer-based prevention programs for homeless youth are complicated by the potential for reinforcing high-risk behaviors among participants. The goal of this study is to understand how homeless youth could be linked to positive peers in prevention programming by understanding where in social and physical space positive peers for homeless youth are located, how these ties are associated with substance use, and the role of social networking technologies (e.g., internet and cell phones) in this process. Personal social network data were collected from 136 homeless adolescents in Los Angeles, CA. Respondents reported on composition of their social networks with respect to: home-based peers and parents (accessed via social networking technology; e.g., the internet, cell phone, texting), homeless peers and agency staff (accessed face-to-face) and whether or not network members were substance-using or non-substance-using. Associations between respondent’s lifetime cocaine, heroin, and methamphetamine use and recent (previous 30 days) alcohol and marijuana use were assessed by the number of non-substance-using versus substance-using ties in multivariate linear regression models. 43% of adolescents reported a non-substance-using home-based tie. More of these ties were associated with less recent alcohol use. 62% of adolescents reported a substance-using homeless tie. More of these ties were associated with more recent marijuana use as well as more lifetime heroin and methamphetamine use. For homeless youth, who are physically disconnected from positive peers, social networking technologies can be used to facilitate the sorts of positive social ties that effective peer-based prevention programs require
    corecore