C57BL/6 life span study: age-related declines in muscle power production and contractile velocity

Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measurement, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (P max), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power generation during concentric contractions in the extensor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P 0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, 50 % P 0). The shape of the force-velocity curve also changed with age (a/P 0 increased). In addition, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.R01 AG017768 - NIA NIH HHS; F31 AG044108 - NIA NIH HHS; T32 AG029796 - NIA NIH HHS; R01 EY15313 - NEI NIH HHS; R01 EY015313 - NEI NIH HH

GALEX: a UV telescope to map the star formation history of the universe

The NASA Small Mission EXplorer GALEX (PI: C.Martin, Caltech) is under development at JPL for launch late 2001. It has been designed to map the history of star formation in the Universe over the redshift range 0-2, a major era where galaxies and gas content evolved dramatically. The expected depth and imaging quality matches the Palomar Observatory Surveys, allowing GALEX to provide the astronomical community with a database of FUV photometric and spectroscopic observations of several million galaxies in the nearby and distant Universe. The 1.24 degree FOV, 50 cm aperture compact Ritchey-Chrétien telescope is equipped with two 65 mm photon-counting detectors. It will perform several surveys of different coverage and depths, that will take advantage of a high throughput UV-transmissive Grism newly developed in France to easily switch between imagery and field spectroscopy modes. A thin aspherized fused silica dichroic component provides simultaneous observations in two UV bands (135-185 nm and 185-300 nm) as well as correction for field aberrations. We shall briefly present the mission science goals, and will describe the optical concept, along with the guidelines and compromises used for its optimization in the context of the "Faster, Better, Cheaper" NASA philosophy, and give a brief development status report

FIREBALL: Instrument pointing and aspect reconstruction

The Faint Intergalactic Redshifted Emission Balloon (FIREBALL) had its first scientific flight in June 2009. The instrument is a 1 meter class balloon-borne telescope equipped with a vacuum-ultraviolet integral field spectrograph intended to detect emission from the inter-galactic medium at redshifts 0.3 < z < 1.0. The scientific goals and the challenging environment place strict constraints on the pointing and tracking systems of the gondola. In this manuscript we briefly review our pointing requirements, discuss the methods and solutions used to meet those requirements, and present the aspect reconstruction results from the first successful scientific flight

Discharge suppression system for a double focusing, atmospheric pressure ionization mass spectrometer

An electrical discharge suppression system for a medium throughput (∼2 l/s) pumping line has been devised that works up to potentials of ±15 kV. This device permits atmospheric pressure ionization sources to be interfaced to high-resolution, magnetic sector mass spectrometers with source potentials of 6-10 k

Targeting multidrug resistance proteins and C-type natriuretic peptide to optimise cyclic GMP signalling in cardiovascular disease

PhDCyclic-3’,5’-guanosine monophosphate (cGMP) is a fundamental intracellular signalling molecule that regulates vascular homeostasis through the tight control of vascular smooth muscle cell (VSMC) reactivity (i.e. vasoconstriction/relaxation) and proliferation. Aberrant VSMC growth and sustained vasoconstriction are hallmarks of cardiovascular disease, exemplified by pulmonary hypertension (PH). Multidrug resistance proteins (MRPs) are membrane bound transporters that facilitate cGMP cellular export thereby representing a potential mechanism that regulates intracellular cGMP-driven signalling. C-type natriuretic peptide (CNP) is an important vasoactive peptide released from the endothelium that maintains vascular homeostasis. CNP binds to natriuretic peptide receptor-B (NPR-B), generating cGMP, and NPR-C, which acts as a clearance receptor removing CNP from the circulation and a signalling pathway regulating vascular function via a cGMP-independent mechanism. Herein, I investigated two separate hypotheses: that MRPs play an important role in maintaining vascular homeostasis, and that endothelium-derived CNP and its cognate receptor, NPR-C, protects against the development of PH. The role of MRPs in regulating vascular homeostasis was investigated using organ bath pharmacology, human VSMC (hVSMC) proliferation and measuring mean arterial blood pressure (MABP) in conscious and anaesthetised mice. To investigate the role of endothelium-derived CNP and NPR-C in PH, male and female CNP and NPR-C knockout (KO) mice were used in two experimental models of PH: hypoxia plus Sugen5416 (SU5416) and bleomycin-induced. The severity of PH was measured using right ventricular systolic pressure (RVSP), MABP, right ventricular hypertrophy (RVH) and pulmonary vascular remodelling. MRP inhibition resulted in concentration-dependent vasorelaxation of mouse aorta per se and increased the potency of cGMP-dependent vessel relaxation in response to activation of both particulate and soluble guanylate cyclases (pGC and sGC). MRP inhibition alone also caused concentration-dependent attenuation of hVSMC proliferation, and enhanced cGMP-mediated attenuation of hVSMC growth via pGC and sGC activation. MRP inhibition per se did not decrease MABP in either anaesthetised or telemeterised mice. However, MRP inhibition did dose-dependently enhance reductions in MABP due to pGC activation in anaesthetised mice. Deletion of endothelial cell-derived CNP (ecCNP KO) in male and female mice did not result in any significant differences in RVSP, RVH or pulmonary vascular remodelling between WT and KO in the hypoxia plus SU5416 model of PH. However, global deletion of NPR-C in both male and female mice caused a significant increase in RVH but not RVSP or vascular remodelling when compared to WT. Both male and female NPR-C KO mice developed significantly increased RVSP compared to WT in the bleomycin-induced model of PH. However, only females exhibited a significant increase in RVH and lung weight in addition to RVSP. In conclusion, MRP inhibition demonstrates potential therapeutic utility to treat cardiovascular diseases by potentiating the vasodilatory and VSMC antiproliferative actions of natriuretic peptides and nitric oxide. Endothelial cellderived CNP is not essential to host protection against PH, whereas its cognate receptor NPR-C demonstrates a cardioprotective capacity. NPR-C attenuates bleomycin-induced PH in both males and females, with a greater effect observed in females. Overall, NPR-C agonism could potentially be used to ameliorate the cardiac and vascular pathology associated with PH.Medical Research Counci

‘I’d best take out life insurance, then.’ Conceptualisations of risk and uncertainty in primary care consultations, and implications for shared decision-making

The main objective of this study is to gain knowledge about interactional factors that support and obstruct mutual risk-assessments and shared decision-making (SDM) in clinical consultations. Through a narrative analysis of verbatim tran- scripts of 28 naturally occurring consultations performed in English National Health Service practices, we explore the ways in which patients and general practitioners conceptualise, construct and negotiate risks related to diagnostic tests and medical treatments. Consultations were sampled from a corpus of 212 consultation transcripts from the One in a Million: Primary care consultations archive on the basis that they contained the word ‘risk(s)’. Most sampled cases relate to cardiovascular conditions and cancer. Drawing on a social constructionist perspective and the relational theory of risk, we found that while GPs talked about mathematical-probabilistic population risk, patients expressed their own experiences of possible future dangers, conceptualised through words like ‘worried’, ‘scared’ and ‘concerned’. Risk objects, defined here as entities to which harmful consequences are conceptually attached, were constructed differently by patients and GPs, especially in relation to cardiovascular risks. Their different rationalities sometimes obstructed any form of mutual risk-assessments. The relational theory of risk proved to be a useful theoretical frame for exploring layers and configurations of risk constructions among patients and clinicians, and for capturing interactional factors that support and obstruct mutual risk-assessments and SDM. For patients to be able to engage in genuine dialogues and make informed decisions about their care, it is paramount for patients and doctors to co-construct patients’ health-risks during clinical encounters

Interpreting U–Pb data from primary and secondary features in lunar zircon

In this paper, we describe primary and secondary microstructures and textural characteristics found in lunar zircon and discuss the relationships between these features and the zircon U–Pb isotopic systems and the significance of these features for understanding lunar processes. Lunar zircons can be classified according to: (i) textural relationships between zircon and surrounding minerals in the host breccias, (ii) the internal microstructures of the zircon grains as identified by optical microscopy, cathodoluminescence (CL) imaging and electron backscattered diffraction (EBSD) mapping and (iii) results of in situ ion microprobe analyses of the Th–U–Pb isotopic systems. Primary zircon can occur as part of a cogenetic mineral assemblage (lithic clast) or as an individual mineral clast and is unzoned, or has sector and/or oscillatory zoning. The age of primary zircon is obtained when multiple ion microprobe analyses across the polished surface of the grain give reproducible and essentially concordant data. A secondary set of microstructures, superimposed on primary zircon, include localised recrystallised domains, localised amorphous domains, crystal–plastic deformation, planar deformation features and fractures, and are associated with impact processes. The first two secondary microstructures often yield internally consistent and close to concordant U–Pb ages that we interpret as dating impact events. Others secondary microstructures such as planar deformation features, crystal–plastic deformation and micro-fractures can provide channels for Pb diffusion and result in partial resetting of the U–Pb isotopic systems

Three-dimensional spectroscopy with a fiber-fed NUV spectrograph

In the context of the NASA balloon borne experiment named Fireball (Faint Intergalactic Redshifted Emission BALLoon) dedicated to map the Intergalactic Medium, we designed a fiber-fed near ultraviolet spectrograph to work in the 200 nm atmospheric transmission window. We first describe the system level optimization leading to the atypical use in UV of a fiber Integral Field Unit at the focus of a one meter diameter parabolic mirror. For the qualification of the design we measured the absolute transmission of an UV polyimide 100 microns core fiber. The fiber bundle made of 400 fibers rearranged in a 50 mm slit feeds an F/2.5 spectrograph based on an Offner Littrow mount. We present the optical performances of this design with a high throughput and a well matched aperture ratio

Thermal history recorded by the Apollo 17 impact melt breccia 73217

Lunar breccia 73217 is composed of plagioclase and pyroxene clasts originating from a single gabbronorite intrusion, mixed with a silica-rich glass interpreted to represent an impact melt. A study of accessory minerals in a thin section from this breccia (73217,52) identified three different types of zircon and anhedral grains of apatite which represent distinct generations of accessory phases and provide a unique opportunity to investigate the thermal history of the sample. Equant, anhedral zircon grains that probably formed in the gabbronorite, referred to as type-1, have consistent U?Pb ages of 4332 7 Ma. A similar age of 4335 5 Ma was obtained from acicular zircon (type-2) grains interpreted to have formed from impact melt. A polycrystalline zircon aggregate (type-3) occurs as a rim around a baddeleyite grain and has a much younger age of 3929 10 Ma, similar to the 3936 17 Ma age of apatite grains found in the thin section. A combined apatite-type-3 zircon age of 3934 12 Ma is proposed as the age of the Serenitatis impact event and associated thermal pulse. X-ray mapping andelectron probe analyses showed that Ti is inhomogeneous in the zircon grains on the sub-micrometer scale. However, model temperatures estimated from SHRIMP analyses of Ti-concentration in the 10 lm diameter spots on the polished surfaces of type-1 and type-2 zircons range between about 1300 and 900 C respectively, whereas Ti-concentrations determined for the type-3 zircon are higher at about 1400?1500 C. A combination of U?Pb ages, Ti-concentration data and detailed imaging and petrographic studies of the zircon grains shows that the gabbronorite parent of the zircon clasts formed shortly before the 4335 5 Ma impact, which mixed the clasts and the felsic melt and projected the sample closer to the surface where fast cooling resulted in the crystallization of acicular zircon (type-2). The 3934 12 Ma Serenitatis event resulted in partial remelting of the glass and formation of polycrystalline zircon (type-3). This event also reset the U?Pb system of apatite, formed merrillite coronas around some apatite grains, and probably re-equilibrated some pyroxenes in the clasts. Although there have been arguments for pre-3.9 Ga impacts based on other types of samples, the age of the acicular zircon at 4335 5 Ma provides the first evidence of impact melt significantly predating the lunar cataclysm. Our data, combined with other chronological results, demonstrate the occurrence of pre-3.9 Ga impacts on the Moon and suggest that the lunar impact history consisted of a series of intense bombardment episodes interspersed with relatively calm periods of low impact flux

The comparative behaviour of apatite-zircon U-Pb systems in Apollo 14 breccias: implications for the thermal history of the Fra Mauro Formation

We report secondary ion mass spectrometry (SIMS) U-Pb analyses of zircon and apatite from four breccia samples from the Apollo 14 landing site. The zircon and apatite grains occur as cogenetic minerals in lithic clasts in two of the breccias and as unrelated mineral clasts in the matrices of the other two. SIMS U-Pb analyses show that the ages of zircon grains range from 4023 ± 24 Ma to 4342 ± 5 Ma, whereas all apatite grains define an isochron corresponding to an age of 3926 ± 3 Ma. The disparity in the ages of cogenetic apatite and zircon demonstrates that the apatite U-Pb systems have been completely reset at 3926 ± 3 Ma, whereas the U-Pb system of zircon has not been noticeably disturbed at this time. The apatite U-Pb age is slightly older than the ages determined by other methods on Apollo 14 materials highlighting need to reconcile decay constants used for the U-Pb, Ar-Ar and Rb-Sr systems. We interpret the apatite age as a time of formation of the Fra Mauro Formation. If the interpretation of this Formation as an Imbrium ejecta is correct, apatite also determines the timing of Imbrium impact. The contrast in the Pb loss behavior of apatite and zircon places constraints on the temperature history of the Apollo 14 breccias and we estimate, from the experimentally determined Pb diffusion constants and an approximation of the original depth of the excavated samples in the Fra Mauro Formation, that the breccias experienced an initial temperature of about 1300-1100 C, but cooled within the first five to ten years