Serum Tumor Necrosis Factor-Alpha Associates with Myocardial Oxygen Demand and Exercise Tolerance in Postmenopausal Women

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest and during two submaximal workloads (i.e., ≈55% and ≈75% VO2max). RPP was calculated by dividing the product of heart rate and systolic blood pressure (via auscultation) by 100. Exercise tolerance corresponded with the cessation of the graded exercise test. During higher-intensity exertion, ≈75% VO2max, multiple linear regression revealed a positive association (r = 0.43; p = 0.015) between TNF-α and RPP while adjusting for maximal heart rate, VO2max, large artery compliance, and percent body fat. Path analyses revealed a significant indirect effect of large artery compliance on exercise tolerance through TNF-α, β = 0.13, CI [0.03, 0.35], indicating greater levels of TNF-α associated with poorer exercise tolerance. These data suggest TNF-α independently associates with myocardial oxygen demand during physical exertion, thus highlighting the utility of higher-intensity efforts to expose important phenomena not apparent at rest. TNF-α also appears to be indirectly associated with the link between large artery compliance and exercise tolerance

Earth-Abundant Metal Catalysis Enabled by Counterion Activation

A precatalyst activation strategy has been developed for earth-abundant metal catalysis enabled by counterion dissociation and demonstrated through alkene hydroboration. Commercially available iron and cobalt tetrafluoroborate salts were found to catalyze the hydroboration of aryl and alkyl alkenes with good functional group tolerance (Fe, 12 substrates; Co, 13 substrates) with three structurally distinct ligands. Key to this endogenous activation was counterion dissociation to generate fluoride which indirectly activates the precatalyst by reaction with pinacol borane

Light and electron microscopical observations of the effects of high-density lipoprotein on growth of Plasmodium falciparum in vitro

Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Parasitology 128 (2004): 577-584, doi:10.1017/S0031182004005025.Human serum high-density lipoprotein (HDL) is necessary and sufficient for the short-term maintenance of Plasmodium falciparum in in vitro culture. However, at high concentrations it is toxic to the parasite. A heat-labile component is apparently responsible for the stage-specific toxicity to parasites within infected erythrocytes 12–42 h after invasion, i.e. during trophozoite maturation. The effects of HDL on parasite metabolism (as determined by nucleic acid synthesis) are evident at about 30 h after invasion. Parasites treated with HDL show gross abnormalities by light and electron microscopy.Professor Hajduk was supported by NIH. Professor Day was supported by a Research Leave Fellowship from The Wellcome Trust. Dr Imrie and Ms Carter were supported by Programme Grant funding awarded to Professor Day from The Wellcome Trust. Dr Ferguson was supported by an equipment grant from The Wellcome Trust

The M-Machine Multicomputer

The M-Machine is an experimental multicomputer being developed to test architectural concepts motivated by the constraints of modern semiconductor technology and the demands of programming systems. The M- Machine computing nodes are connected with a 3-D mesh network; each node is a multithreaded processor incorporating 12 function units, on-chip cache, and local memory. The multiple function units are used to exploit both instruction-level and thread-level parallelism. A user accessible message passing system yields fast communication and synchronization between nodes. Rapid access to remote memory is provided transparently to the user with a combination of hardware and software mechanisms. This paper presents the architecture of the M-Machine and describes how its mechanisms maximize both single thread performance and overall system throughput

Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3)

We describe a family with autosomal dominant inheritance of increased body iron stores characterized by raised serum ferritin concentration and normal transferrin saturation. Liver biopsy showed iron deposition in Kupffer cells without fibrosis. The clinical features of HFE-related hemochromatosis were absent, as were the Cys282Tyr and His63Asp mutations. Venesection therapy was poorly tolerated, suggesting a defect in iron release from reticuloendothelial stores. A 3-base pair deletion in exon 5 of the ferroportin 1 gene (SLC11A3) predicting Val162 deletion was found in affected members, but not in unaffected individuals or in 100 control subjects. Consensus structural predictions of the transmembrane helices showed that the deletion is in the extracellular loop between the third and fourth predicted transmembrane helices and lies within a spatial cluster of other known ferroportin 1 mutations. These results indicate that this extracellular cluster is functionally important for iron transport, and its disruption leads to iron overload

Repetitive sequence variation and dynamics in the ribosomal DNA array of Saccharomyces cerevisiae as revealed by whole-genome resequencing

Ribosomal DNA (rDNA) plays a key role in ribosome biogenesis, encoding genes for the structural RNA components of this important cellular organelle. These genes are vital for efficient functioning of the cellular protein synthesis machinery and as such are highly conserved and normally present in high copy numbers. In the baker's yeast Saccharomyces cerevisiae, there are more than 100 rDNA repeats located at a single locus on chromosome XII. Stability and sequence homogeneity of the rDNA array is essential for function, and this is achieved primarily by the mechanism of gene conversion. Detecting variation within these arrays is extremely problematic due to their large size and repetitive structure. In an attempt to address this, we have analyzed over 35 Mbp of rDNA sequence obtained from whole-genome shotgun sequencing (WGSS) of 34 strains of S. cerevisiae. Contrary to expectation, we find significant rDNA sequence variation exists within individual genomes. Many of the detected polymorphisms are not fully resolved. For this type of sequence variation, we introduce the term partial single nucleotide polymorphism, or pSNP. Comparative analysis of the complete data set reveals that different S. cerevisiae genomes possess different patterns of rDNA polymorphism, with much of the variation located within the rapidly evolving nontranscribed intergenic spacer (IGS) region. Furthermore, we find that strains known to have either structured or mosaic/hybrid genomes can be distinguished from one another based on rDNA pSNP number, indicating that pSNP dynamics may provide a reliable new measure of genome origin and stability

The intrinsic and interstellar broad-band linear polarization of nearby FGK dwarfs

We present linear polarization measurements of nearby FGK dwarfs to parts-per-million (ppm) precision. Before making any allowance for interstellar polarization, we found that the active stars within the sample have a mean polarization of 28.5 ± 2.2 ppm, while the inactive stars have a mean of 9.6 ± 1.5 ppm. Amongst inactive stars, we initially found no difference between debris disc host stars (9.1 ± 2.5 ppm) and the other FGK dwarfs (9.9 ± 1.9 ppm). We develop a model for the magnitude and direction of interstellar polarization for nearby stars. When we correct the observations for the estimated interstellar polarization, we obtain 23.0 ± 2.2 ppm for the active stars, 7.8 ± 2.9 ppm for the inactive debris disc host stars and 2.9 ± 1.9 ppm for the other inactive stars. The data indicate that whilst some debris disc host stars are intrinsically polarized most inactive FGK dwarfs have negligible intrinsic polarization, but that active dwarfs have intrinsic polarization at levels ranging up to ∼45 ppm. We briefly consider a number of mechanisms, and suggest that differential saturation of spectral lines in the presence of magnetic fields is best able to explain the polarization seen in active dwarfs. The results have implications for current attempts to detect polarized reflected light from hot Jupiters by looking at the combined light of the star and planet

Modeling 5 Years of Subglacial Lake Activity in the MacAyeal Ice Stream (Antarctica) Catchment Through Assimilation of ICESat Laser Altimetry

Subglacial lakes beneath Antarctica’s fast-moving ice streams are known to undergo ~1km3 volume changes on annual timescales. Focusing on the MacAyeal Ice Stream (MacIS) lake system, we create a simple model for the response of subglacial water distribution to lake discharge events through assimilation of lake volume changes estimated from Ice, Cloud and land Elevation Satellite (ICESat) laser altimetry. We construct a steady-state water transport model in which known subglacial lakes are treated as either sinks or sources depending on the ICESat-derived filling or drainingrates. The modeled volume change rates of five large subglacial lakes in the downstream portion of MacIS are shown to be consistent with observed filling rates if the dynamics of all upstream lakes are considered. However, the variable filling rate of the northernmost lake suggests the presence of an undetected lake of similar size upstream. Overall, we show that, for this fast-flowing ice stream, most subglacial lakes receive \u3e90% of their water from distant distributed sources throughout the catchment, and we confirm that water is transported from regions of net basal melt to regions of net basal freezing. Our study provides a geophysically based means of validating subglacial water models in Antarctica and is a potential way to parameterize subglacial lake discharge events in large-scale ice-sheet models where adequate data are available

Stochastic Model for Surface Erosion Via Ion-Sputtering: Dynamical Evolution from Ripple Morphology to Rough Morphology

Surfaces eroded by ion-sputtering are sometimes observed to develop morphologies which are either ripple (periodic), or rough (non-periodic). We introduce a discrete stochastic model that allows us to interpret these experimental observations within a unified framework. We find that a periodic ripple morphology characterizes the initial stages of the evolution, whereas the surface displays self-affine scaling in the later time regime. Further, we argue that the stochastic continuum equation describing the surface height is a noisy version of the Kuramoto-Sivashinsky equation.Comment: 4 pages, 7 postscript figs., Revtex, to appear in Phys. Rev. Let

Detection of Planetary and Stellar Companions to Neighboring Stars via a Combination of Radial Velocity and Direct Imaging Techniques

13 pages, 6 figures, 4 tables, accepted for publication in the Astronomical Journal (submitted 25 Feb 2019; accepted 28 April 2019). Machine readable tables and Posteriors from the RadVel fits are available here: http://stephenkane.net/rvfits.tarThe sensitivities of radial velocity (RV) surveys for exoplanet detection are extending to increasingly longer orbital periods, where companions with periods of several years are now being regularly discovered. Companions with orbital periods that exceed the duration of the survey manifest in the data as an incomplete orbit or linear trend, a feature that can either present as the sole detectable companion to the host star, or as an additional signal overlain on the signatures of previously discovered companion(s). A diagnostic that can confirm or constrain scenarios in which the trend is caused by an unseen stellar rather than planetary companion is the use of high-contrast imaging observations. Here, we present RV data from the Anglo-Australian Planet Search (AAPS) for 20 stars that show evidence of orbiting companions. Of these, six companions have resolved orbits, with three that lie in the planetary regime. Two of these (HD 92987b and HD 221420b) are new discoveries. Follow-up observations using the Differential Speckle Survey Instrument (DSSI) on the Gemini South telescope revealed that 5 of the 20 monitored companions are likely stellar in nature. We use the sensitivity of the AAPS and DSSI data to place constraints on the mass of the companions for the remaining systems. Our analysis shows that a planetary-mass companion provides the most likely self-consistent explanation of the data for many of the remaining systems.Peer reviewedFinal Accepted Versio