Brain natriuretic peptide and NT-proBNP levels reflect pulmonary artery systolic pressure in trekkers at high altitude.

Our objective was to evaluate the utility of the natriuretic peptides BNP (brain natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had BNP and NT-proBNP assayed and simultaneous echocardiographic assessment of PASP performed during a trek to 5150 m. PASP increased significantly (p=0.006) with ascent from 24+/-4 to 39+/-11 mm Hg at 5150 m. At 5150 m those with a PASP>/=40 mm Hg (n=8) (versus those with PASP/=400 pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9+/-7.5 vs. 32.2+/-6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP, a central feature of high altitude pulmonary oedema, at HA

Metallurgical Mechanisms Controlling Mechanical Properties of Aluminum Alloy 2219 Produced By Electron Beam Freeform Fabrication

The electron beam freeform fabrication (EBF3) layer-additive manufacturing process has been developed to directly fabricate complex geometry components. EBF3 introduces metal wire into a molten pool created on the surface of a substrate by a focused electron beam. Part geometry is achieved by translating the substrate with respect to the beam to build the part one layer at a time. Tensile properties have been demonstrated for electron beam deposited aluminum and titanium alloys that are comparable to wrought products, although the microstructures of the deposits exhibit features more typical of cast material. Understanding the metallurgical mechanisms controlling mechanical properties is essential to maximizing application of the EBF3 process. In the current study, mechanical properties and resulting microstructures were examined for aluminum alloy 2219 fabricated over a range of EBF3 process variables. Material performance was evaluated based on tensile properties and results were compared with properties of Al 2219 wrought products. Unique microstructures were observed within the deposited layers and at interlayer boundaries, which varied within the deposit height due to microstructural evolution associated with the complex thermal history experienced during subsequent layer deposition. Microstructures exhibited irregularly shaped grains, typically with interior dendritic structures, which were described based on overall grain size, morphology, distribution, and dendrite spacing, and were correlated with deposition parameters. Fracture features were compared with microstructural elements to define fracture paths and aid in definition of basic processing-microstructure-property correlations

Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness.

Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS

Human AlkB Homolog ABH8 Is a tRNA Methyltransferase Required for Wobble Uridine Modification and DNA Damage Survival

tRNA nucleosides are extensively modified to ensure their proper function in translation. However, many of the enzymes responsible for tRNA modifications in mammals await identification. Here, we show that human AlkB homolog 8 (ABH8) catalyzes tRNA methylation to generate 5-methylcarboxymethyl uridine (mcm[superscript 5]U) at the wobble position of certain tRNAs, a critical anticodon loop modification linked to DNA damage survival. We find that ABH8 interacts specifically with tRNAs containing mcm5U and that purified ABH8 complexes methylate RNA in vitro. Significantly, ABH8 depletion in human cells reduces endogenous levels of mcm[superscript 5]U in RNA and increases cellular sensitivity to DNA-damaging agents. Moreover, DNA-damaging agents induce ABH8 expression in an ATM-dependent manner. These results expand the role of mammalian AlkB proteins beyond that of direct DNA repair and support a regulatory mechanism in the DNA damage response pathway involving modulation of tRNA modification.United States. National Institutes of Health (grant CA055042)United States. National Institutes of Health (grant ES002109)United States. National Institutes of Health (grant ES01701)National Institutes of Health (U.S.). Intramural Research ProgramWestaway Research FundNational Center for Research Resources (U.S.) (grant S10-RR023783

Structural and Magnetic Properties of Trigonal Iron

First principles calculations of the electronic structure of trigonal iron were performed using density function theory. The results are used to predict lattice spacings, magnetic moments and elastic properties; these are in good agreement with experiment for both the bcc and fcc structures. We find however, that in extracting these quantities great care must be taken in interpreting numerical fits to the calculated total energies. In addition, the results for bulk iron give insight into the properties of thin iron films. Thin films grown on substrates with mismatched lattice constants often have non-cubic symmetry. If they are thicker than a few monolayers their electronic structure is similar to a bulk material with an appropriately distorted geometry, as in our trigonal calculations. We recast our bulk results in terms of an iron film grown on the (111) surface of an fcc substrate, and find the predicted strain energies and moments accurately reflect the trends for iron growth on a variety of substrates.Comment: 11 pages, RevTeX,4 tar'd,compressed, uuencoded Postscript figure

Charitable Food Systems' Capacity to Address Food Insecurity: An Australian Capital City Audit.

Australian efforts to address food insecurity are delivered by a charitable food system (CFS) which fails to meet demand. The scope and nature of the CFS is unknown. This study audits the organisational capacity of the CFS within the 10.9 square kilometres of inner-city Perth, Western Australia. A desktop analysis of services and 12 face-to-face interviews with representatives from CFS organisations was conducted. All CFS organisations were not-for⁻profit and guided by humanitarian or faith-based values. The CFS comprised three indirect services (IS) sourcing, banking and/or distributing food to 15 direct services (DS) providing food to recipients. DS offered 30 different food services at 34 locations feeding over 5670 people/week via 16 models including mobile and seated meals, food parcels, supermarket vouchers, and food pantries. Volunteer to paid staff ratios were 33:1 (DS) and 19:1 (IS). System-wide, food was mainly donated and most funding was philanthropic. Only three organisations received government funds. No organisation had a nutrition policy. The organisational capacity of the CFS was precarious due to unreliable, insufficient and inappropriate financial, human and food resources and structures. System-wide reforms are needed to ensure adequate and appropriate food relief for Australians experiencing food insecurity

A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress

Decades of study have revealed more than 100 ribonucleoside structures incorporated as post-transcriptional modifications mainly in tRNA and rRNA, yet the larger functional dynamics of this conserved system are unclear. To this end, we developed a highly precise mass spectrometric method to quantify tRNA modifications in Saccharomyces cerevisiae. Our approach revealed several novel biosynthetic pathways for RNA modifications and led to the discovery of signature changes in the spectrum of tRNA modifications in the damage response to mechanistically different toxicants. This is illustrated with the RNA modifications Cm, m[superscript 5]C, and m[superscript 2][subscript 2]G, which increase following hydrogen peroxide exposure but decrease or are unaffected by exposure to methylmethane sulfonate, arsenite, and hypochlorite. Cytotoxic hypersensitivity to hydrogen peroxide is conferred by loss of enzymes catalyzing the formation of Cm, m[superscript 5]C, and m[superscript 2][subscript 2]G, which demonstrates that tRNA modifications are critical features of the cellular stress response. The results of our study support a general model of dynamic control of tRNA modifications in cellular response pathways and add to the growing repertoire of mechanisms controlling translational responses in cells.National Institute of Environmental Health Sciences (ES002109)National Institute of Environmental Health Sciences (ES017010)National Institute of Environmental Health Sciences (ES015037)National Cancer Institute (U.S.) (CA026731)National Center for Research Resources (U.S.) (RR023783)Singapore-MIT Alliance for Research and Technolog

Strained tetragonal states and Bain paths in metals

Paths of tetragonal states between two phases of a material, such as bcc and fcc, are called Bain paths. Two simple Bain paths can be defined in terms of special imposed stresses, one of which applies directly to strained epitaxial films. Each path goes far into the range of nonlinear elasticity and reaches a range of structural parameters in which the structure is inherently unstable. In this paper we identify and analyze the general properties of these paths by density functional theory. Special examples include vanadium, cobalt and copper, and the epitaxial path is used to identify an epitaxial film as related uniquely to a bulk phase.Comment: RevTeX, 4 pages, 4 figures, submitted to Phys. Rev. Let

Surface relaxation and ferromagnetism of Rh(001)

The significant discrepancy between first-principles calculations and experimental analyses for the relaxation of the (001) surface of rhodium has been a puzzle for some years. In this paper we present density functional theory calculations using the local-density approximation and the generalized gradient approximation of the exchange-correlation functional. We investigate the thermal expansion of the surface and the possibility of surface magnetism. The results throw light on several, hitherto overlooked, aspects of metal surfaces. We find, that, when the free energy is considered, density-functional theory provides results in good agreement with experiments.Comment: 6 pages, 4 figures, submitted to Phys. Rev. Lett. (April 28, 1996

Structure and dynamics of Rh surfaces

Lattice relaxations, surface phonon spectra, surface energies, and work functions are calculated for Rh(100) and Rh(110) surfaces using density-functional theory and the full-potential linearized augmented plane wave method. Both, the local-density approximation and the generalized gradient approximation to the exchange-correlation functional are considered. The force constants are obtained from the directly calculated atomic forces, and the temperature dependence of the surface relaxation is evaluated by minimizing the free energy of the system. The anharmonicity of the atomic vibrations is taken into account within the quasiharmonic approximation. The importance of contributions from different phonons to the surface relaxation is analyzed.Comment: 9 pages, 7 figures, scheduled to appear in Phys. Rev. B, Feb. 15 (1998). Other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm