8-Chloroadenosine induces apoptosis in human coronary artery endothelial cells through the activation of the unfolded protein response

© 2019 The Authors Infiltration of leukocytes within the vessel at sites of inflammation and the subsequent generation of myeloperoxidase-derived oxidants, including hypochlorous acid, are key characteristics of atherosclerosis. Hypochlorous acid is a potent oxidant that reacts readily with most biological molecules, including DNA and RNA. This results in nucleic acid modification and the formation of different chlorinated products. These products have been used as biomarkers of inflammation, owing to their presence in elevated amounts in different inflammatory fluids and diseased tissue, including atherosclerotic lesions. However, it is not clear whether these materials are simply biomarkers, or could also play a role in the development of chronic inflammatory pathologies. In this study, we examined the reactivity of different chlorinated nucleosides with human coronary artery endothelial cells (HCAEC). Evidence was obtained for the incorporation of each chlorinated nucleoside into the cellular RNA or DNA. However, only 8-chloro-adenosine (8ClA) had a significant effect on the cell viability and metabolic activity. Exposure of HCAEC to 8ClA decreased glycolysis, and resulted in a reduction in ATP, with a corresponding increase in the chlorinated analogue, 8Cl-ATP in the nucleotide pool. 8ClA also induced sustained endoplasmic reticulum stress within the HCAEC, which resulted in activation of the unfolded protein response, the altered expression of antioxidant genes and culminated in the release of calcium into the cytosol and cell death by apoptosis. Taken together, these data provide new insight into pathways by which myeloperoxidase activity and resultant hypochlorous acid generation could promote endothelial cell damage during chronic inflammation, which could be relevant to the progression of atherosclerosis

Time transfer between the Goddard Optical Research Facility and the U.S. Naval Observatory using 100 picosecond laser pulses

A horizontal two-way time comparison link in air between the University of Maryland laser ranging and time transfer equipment at the Goddard Optical Research Facility (GORF) 1.2 m telescope and the Time Services Division of the U.S. Naval Observatory (USNO) was established. Flat mirrors of 25 cm and 30 cm diameter respectively were placed on top of the Washington Cathedral and on a water tower at the Beltsville Agricultural Research Center. Two optical corner reflectors at the USNO reflect the laser pulses back to the GORF. Light pulses of 100 ps duration and an energy of several hundred microjoules are sent at the rate of 10 pulses per second. The detection at the USNO is by means of an RCA C30902E avalanche photodiode and the timing is accomplished by an HP 5370A computing counter and an HP 1000 computer with respect to a 10 pps pulse train from the Master Clock

How strongly do word reading times and lexical decision times correlate? Combining data from eye movement corpora and megastudies

We assess the amount of shared variance between three measures of visual word recognition latencies: eye movement latencies, lexical decision times and naming times. After partialling out the effects of word frequency and word length, two well-documented predictors of word recognition latencies, we see that 7-44% of the variance is uniquely shared between lexical decision times and naming times, depending on the frequency range of the words used. A similar analysis of eye movement latencies shows that the percentage of variance they uniquely share either with lexical decision times or with naming times is much lower. It is 5 – 17% for gaze durations and lexical decision times in studies with target words presented in neutral sentences, but drops to .2% for corpus studies in which eye movements to all words are analysed. Correlations between gaze durations and naming latencies are lower still. These findings suggest that processing times in isolated word processing and continuous text reading are affected by specific task demands and presentation format, and that lexical decision times and naming times are not very informative in predicting eye movement latencies in text reading once the effect of word frequency and word length are taken into account. The difference between controlled experiments and natural reading suggests that reading strategies and stimulus materials may determine the degree to which the immediacy-of-processing assumption and the eye-mind assumption apply. Fixation times are more likely to exclusively reflect the lexical processing of the currently fixated word in controlled studies with unpredictable target words rather than in natural reading of sentences or texts

Effects of exoplanetary gravity on human locomotor ability

At some point in the future, if mankind hopes to settle planets outside the Solar System, it will be crucial to determine the range of planetary conditions under which human beings could survive and function. In this article, we apply physical considerations to future exoplanetary biology to determine the limitations which gravity imposes on several systems governing the human body. Initially, we examine the ultimate limits at which the human skeleton breaks and muscles become unable to lift the body from the ground. We also produce a new model for the energetic expenditure of walking, by modelling the leg as an inverted pendulum. Both approaches conclude that, with rigorous training, humans could perform normal locomotion at gravity no higher than 4 $g_{\textrm{Earth}}$.Comment: 12 pages, 4 figures, to be published in The Physics Teache

Far-Infrared Observations Of A Massive Cluster Forming In The Monoceros R2 Filament Hub

We present far-infrared observations of Monoceros R2 (a giant molecular cloud at approximately 830 pc distance, containing several sites of active star formation), as observed at 70 μm, 160 μm, 250 μm, 350 μm, and 500 μm by the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) instruments on the Herschel Space Observatory as part of the Herschel imaging survey of OB young stellar objects (HOBYS) Key programme. The Herschel data are complemented by SCUBA-2 data in the submillimetre range, and WISE and Spitzer data in the mid-infrared. In addition, C18O data from the IRAM 30-m Telescope are presented, and used for kinematic information. Sources were extracted from the maps with getsources, and from the fluxes measured, spectral energy distributions were constructed, allowing measurements of source mass and dust temperature. Of177 Herschel sources robustly detected in the region (a detection with high signal-to-noise and low axis ratio at multiple wavelengths), including protostars and starless cores, 29 are found in a filamentary hub at the centre of the region (a little over 1% of the observed area). These objects are on average smaller, more massive, and more luminous than those in the surrounding regions (which together suggest that they are at a later stage of evolution), a result that cannot be explained entirely by selection effects. These results suggest a picture in which the hub may have begun star formation at a point significantly earlier than the outer regions, possibly forming as a result of feedback from earlier star formation. Furthermore, the hub may be sustaining its star formation by accreting material from the surrounding filaments

The design and commissioning of the MICE upstream time-of-flight system

In the MICE experiment at RAL the upstream time-of-flight detectors are used for particle identification in the incoming muon beam, for the experiment trigger and for a precise timing (sigma_t ~ 50 ps) with respect to the accelerating RF cavities working at 201 MHz. The construction of the upstream section of the MICE time-of-flight system and the tests done to characterize its individual components are shown. Detector timing resolutions ~50-60 ps were achieved. Test beam performance and preliminary results obtained with beam at RAL are reported.Comment: accepted on Nuclear Instruments and Methods

Exploring the measurement of markedness and its relationship with other linguistic variables

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse

MageComet—web application for harmonizing existing large-scale experiment descriptions

Motivation: Meta-analysis of large gene expression datasets obtained from public repositories requires consistently annotated data. Curation of such experiments, however, is an expert activity which involves repetitive manipulation of text. Existing tools for automated curation are few, which bottleneck the analysis pipeline

Completing the bedrock mapping of southern Baffin Island, Nunavut; plutonic suites and regional stratigraphy

This paper summarizes the field observations and initial interpretations following eight weeks of regional and targeted bed- rock mapping on south-central Baffin Island, Nunavut. The 2015 field campaign completes a two-decade mission to update the geoscience knowledge for the whole of Baffin Island south of latitude 70°N. The bedrock in the area is dominated by a Paleoproterozoic metaplutonic suite, ranging in composition from gabbro to syenogranite, with crosscutting relations indi- cating a progression from mafic to silicic magmatism. Phase-equilibria modelling reveals that the prevailing upper-amphi- bolite– to lower-granulite–facies metamorphic conditions overlap the stability limits of magnetite and orthopyroxene for a typical granitoid bulk composition, which is consistent with field observations of the discontinuous presence of both phases throughout the map area. This result is also consistent with regional aeromagnetic data that show complex structures within relatively homogeneous map units, which are primarily attributed to variations in the abundance of magnetite. The granitoid rocks are interpreted as part of the middle Paleoproterozoic Cumberland Batholith. Metasedimentary rocks, including quartzite, pelite, marble and metagreywacke, are present as enclaves and screens within and between plutonic bodies. An examination of the ‘ghost’stratigraphy suggests that the metasedimentary rocks through- out most of the map area can be correlated with the middle Paleoproterozoic Lake Harbour Group, except in the northeast, where the unique presence of greywacke suggests a middle Paleoproterozoic Piling Group affinity. This transition in strata is consistent with the proposal that a middle Paleoproterozoic tectonic suture (the Baffin suture) associated with the Trans- Hudson Orogen runs through Cumberland Sound. Completion of the bedrock mapping in southern Baffin Island indicates that the region offers a world-class exposure of a reworked Paleoproterozoic convergent margin, which affords valuable in- sight into a variety of magmatic and tectonic processes that can be applied to younger collisional belt

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization’s products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention