Predominantly Non-Solar Origin of Nitrogen in Lunar Soils

Simultaneous static-mode mass spectrometric measurements of nitrogen, carbon, helium, neon, and argon, extracted from the same aliquot of sample by high-resolution stepped combustion, have been made for a suite of five lunar soils. Noble gas isotope ratios show that the majority of noble gases are derived from a solar wind source; for example, at peak release temperatures of 500–600 °C,21Ne/22Ne = 0.0313 ± 0.0007 to 0.0333 ± 0.0007, and 20Ne/22Ne = 11.48 ± 0.05 to 12.43 ± 0.07, with values at the lowest temperature steps less fractionated during implantation from, and therefore even closer to, solar values (21Ne/22NeSW = 0.03361 ± 0.00018 and 20Ne/22NeSW = 14.001 ± 0.042 (Pepin et al., 2012)). Despite the co-release of nitrogen and solar wind argon, measured nitrogen isotopic signatures at each temperature step, whilst variable, are significantly more enriched in 15N compared to the measured solar wind nitrogen value from the Genesis mission. Therefore, mixing between a 15N-enriched non-solar planetary nitrogen source with solar wind nitrogen is required to explain the measured isotopic values from the stepped combustion analysis of lunar soils. Binary mixing calculations, made under different assumptions about the degree of loss of solar wind 36Ar, reveal that the majority (up to 98%) of the nitrogen released is derived from a non-solar source. The range of modelled non-solar end-member nitrogen compositions required to satisfy the measuredδ15N values varies between samples and temperature steps from +5‰ up to +300‰, or between +87‰ and +160‰ for bulk samples. This range of modelled isotopic compositions for the non-solar source of nitrogen encompasses measured values for several different groups of carbonaceous chondrite, as well as IDPs

An XMM-Newton observation of the galaxy group MKW 4

We present an X-ray study of the galaxy group or poor cluster MKW 4. Working with XMM data we examine the distribution and properties of the hot gas which makes up the group halo. The inner halo shows some signs of structure, with circular or elliptical beta models providing a poor fit to the surface brightness profile. This may be evidence of large scale motion in the inner halo, but we do not find evidence of sharp fronts or edges in the emission. The temperature of the halo declines in the core, with deprojected spectral fits showing a central temperature of ~1.3 keV compared to ~3 keV at 100 kpc. In the central ~30 kpc of the group multi-temperature spectral models are required to fit the data, but they indicate a lack of gas at low temperatures. Steady state cooling flow models provide poor fits to the inner regions of the group and the estimated cooling time of the gas is long except within the central dominant galaxy, NGC 4073. Abundance profiles show a sharp increase in the core of the group, with mean abundance rising by a factor of two in the centre of NGC 4073. Fitting individual elements shows the same trend, with high values of Fe, Si and S in the core. We estimate that ~50% of the Fe in the central 40 kpc was injected by SNIa, in agreement with previous ASCA studies. Using our best fitting surface brightness and temperature models, we calculate the mass, gas fraction, entropy and mass-to-light ratio of the group. At 100 kpc (~0.1 virial radii) the total mass and gas entropy of the system (~2x10^13 Msol and ~300 keV cm^2) are quite comparable to those of other systems of similar temperature, but the gas fraction is rather low (~1%). We conclude that MKW 4 is a fairly relaxed group, which has developed a strong central temperature gradient but not a large-scale cooling flow.Comment: 17 pages, 9 postscript figures, accepted for publication in MNRA

Internal mammary artery dilatation in a patient with aortic coarctation, aortic stenosis, and coronary disease. Case report

The ideal surgical approach is unclear in adult patients with coarctation of the aorta that is associated with other cardiovascular pathologies that require intervention. Standard median sternotomy allows simultaneous, coronary revascularization surgery, valve replacement and repair of aortic coarctation. However the collateral circulation and the anatomy of the mammary arteries must be determined, to avoid possible complications. We report a case of a 69 year-old man with aortic coarctation, aortic stenosis, coronary artery disease and internal mammary artery dilatation who underwent concomitant surgical procedures through a median sternotomy

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase III BEACON trial

Background: Health-related quality of life (HRQoL) enhances understanding of treatment effects that impact clinical decision-making. Although the primary end-point was not achieved, the BEACON (BrEAst Cancer Outcomes with NKTR-102) trial established etirinotecan pegol, a long-acting topoisomerase-1 (TOP1) inhibitor, as a promising therapeutic for patients with advanced/metastatic breast cancer (MBC) achieving clinically meaningful benefits in median overall survival (OS) for patients with stable brain metastases, with liver metastases or ≥ 2 sites of metastatic disease compared to treatment of physician’s choice (TPC). Reported herein are the findings from the preplanned secondary end-point of HRQoL. Patients and methods: HRQoL, assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (version 3.0) supplemented by the breast cancer-specific Quality of Life Questionnaire (QLQ-BR23), was evaluated post randomisation in 733 of 852 patients with either anthracycline-, taxane- and capecitabine-pretreated locally recurrent or MBC randomised to etirinotecan pegol (n = 378; 145 mg/m2 every 3 weeks (q3wk)) or single-agent TPC (n = 355). Patients completed assessments at screening, every 8 weeks (q8wk) during treatment, and end-of-treatment. Changes from baseline were analysed, and the proportions of patients achieving differences (≥5 points) in HRQoL scores were compared. Results: Differences were seen favouring etirinotecan pegol up to 32 weeks for global health status (GHS) and physical functioning scales (P < 0.02); numerical improvement was reported in other functional scales. The findings from HRQoL symptom scales were consistent with adverse event profiles; etirinotecan pegol was associated with worsening gastrointestinal symptoms whereas TPC was associated with worsened dyspnoea and other systemic side-effects. Analysis of GHS and physical functioning at disease progression showed a decline in HRQoL in both treatment arms, with a mean change from baseline of −9.4 and −10.8 points, respectively. Conclusion: There was evidence of benefit associated with etirinotecan pegol compared with current standard of care agents in multiple HRQoL measurements, including global health status and physical functioning, despite worse gastrointestinal symptoms (e.g. diarrhoea). Patients in both arms had a decline in HRQoL at disease progression. Study number: NCT01492101

Cell‐penetrating peptides: Achievements and challenges in application for cancer treatment

One of the major hurdles to cure cancer lies in the low potency of currently available drugs, which could eventually be solved by using more potent therapeutic macromolecules, such as proteins or genes. However, although these macromolecules possess greater potency inside the cancer cells, the barely permeable cell membrane remains a formidable barrier to exert their efficacy. A widely used strategy is to use cell penetrating peptides (CPPs) to improve their intracellular uptake. Since the discovery of the first CPP, numerous CPPs have been derived from natural or synthesized products. Both in vitro and in vivo studies have demonstrated that those CPPs are highly efficient in transducing cargoes into almost all cell types. Therefore, to date, CPPs have been widely used for intracellular delivery of various cargoes, including peptides, proteins, genes, and even nanoparticles. In addition, recently, based on the successes of CPPs in cellular studies, their applications in vivo have been actively pursued. This review will focus on the advanced applications of CPP‐based in vivo delivery of therapeutics (e.g., small molecule drugs, proteins, and genes). In addition, we will highlight certain updated applications of CPPs for intracellular delivery of nanoparticulate drug carriers, as well as several “smart” strategies for tumor targeted delivery of CPP‐cargoes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 575–587, 2014.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102051/1/jbma34859.pd

Record of forearc devolatilization in low-T, high-P/T metasedimentary suites: Significance for models of convergent margin chemical cycling

[1] The Franciscan Complex (Coast Ranges and Diablo Range, California) and the Western Baja Terrane (WBT; Baja California, Mexico) were metamorphosed along high-P/T paths like those experienced in many active subduction zones, recording peak conditions up to ∼1 GPa and 300°C. Franciscan and WBT metasedimentary rocks are similar in lithology and geochemistry to clastic sediments outboard of many subduction zones. These metamorphic suites provide evidence regarding devolatilization history experienced by subducting sediments, information that is needed to mass-balance the inputs of materials into subduction zones with their respective outputs. Analyzed samples have lower total volatile contents than their likely protoliths. Little variation in LOI among similar lithologies at differing metamorphic grades, suggests that loss of structurally bound water occurred during early clay-mineral transformations. Finely disseminated carbonate is present in the lowest-grade rocks, but absent in all higher-grade rocks. δ13CVPDB of reduced-C is uniform in the lower-grade Franciscan samples (mean = −25.1‰, 1σ = 0.4‰), but varies in higher-grade rocks (−28.8 to −21.9‰). This likely reflects a combination of devolatilization and C-isotope exchange, between organic and carbonate reservoirs. Nitrogen concentration ranges from 102 to 891 ppm, with δ15Nair of +0.1 to +3.0‰ (n = 35); this organic-like δ15N probably represents an efficient transfer of N from decaying organic matter to reacting clay minerals. The lowest-grade rocks in the Coastal Belt have elevated carbonate contents and correlated N-δ15N variations, and exhibit the most uniform δ13C and C/N, all consistent with these rocks having experienced less devolatilization. Most fluid-mobile trace elements are present at concentrations indistinguishable from protoliths. Suggesting that, despite apparent loss of much clay-bound H2O and CO2 from diagenetic cements (combined, <5–10 wt. %), most fluid-mobile trace elements are retained to depths of up to ∼40 km. Organic-like δ15N, lower than that of many seafloor sediments, is consistent with some loss of adsorbed N (perhaps as NO3−) during early stages of diagenesis. The efficient entrainment of fluid-mobile elements to depths of at least 40 km in these relatively cool subduction zone settings lends credence to models invoking transfer of these elements to the subarc mantle

Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina

Natural IgM antibodies in diverse species recognize conserved carbohydrates in fungal cell walls and influence early host defense against Pneumocystis in mice

Carbon release from submarine seeps at the Costa Rica fore arc: implications for the volatile cycle at the Central America convergent margin

We report total dissolved inorganic carbon (DIC) abundances and isotope ratios, as well as helium isotope ratios (3He/4He), of cold seep fluids sampled at the Costa Rica fore arc in order to evaluate the extent of carbon loss from the submarine segment of the Central America convergent margin. Seep fluids were collected over a 12 month period at Mound 11, Mound 12, and Jaco Scar using copper tubing attached to submarine flux meters operating in continuous pumping mode. The fluids show minimum 3He/4He ratios of 1.3 RA (where RA is air 3He/4He), consistent with a small but discernable contribution of mantle-derived helium. At Mound 11, δ13C∑CO2 values between −23.9‰ and −11.6‰ indicate that DIC is predominantly derived from deep methanogenesis and is carried to the surface by fluids derived from sediments of the subducting slab. In contrast, at Mound 12, most of the ascending dissolved methane is oxidized due to lower flow rates, giving extremely low δ13C∑CO2 values ranging from −68.2‰ to −60.3‰. We estimate that the carbon flux (CO2 plus methane) through submarine fluid venting at the outer fore arc is 8.0 × 105 g C km−1 yr−1, which is virtually negligible compared to the total sedimentary carbon input to the margin and the output at the volcanic front. Unless there is a significant but hitherto unidentified carbon flux at the inner fore arc, the implication is that most of the carbon being subducted in Costa Rica must be transferred to the (deeper) mantle, i.e., beyond the depth of arc magma generation

A framework to assess biogeochemical response to ecosystem disturbance using nutrient partitioning ratios

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecosystems 19 (2016): 387-395, doi:10.1007/s10021-015-9934-1.Disturbances affect almost all terrestrial ecosystems, but it has been difficult to identify general principles regarding these influences. To improve our understanding of the long-term consequences of disturbance on terrestrial ecosystems, we present a conceptual framework that analyzes disturbances by their biogeochemical impacts. We posit that the ratio of soil and plant nutrient stocks in mature ecosystems represents a characteristic site property. Focusing on nitrogen (N), we hypothesize that this partitioning ratio (soil N: plant N) will undergo a predictable trajectory after disturbance. We investigate the nature of this partitioning ratio with three approaches: (1) nutrient stock data from forested ecosystems in North America, (2) a process-based ecosystem model, and (3) conceptual shifts in site nutrient availability with altered disturbance frequency. Partitioning ratios could be applied to a variety of ecosystems and successional states, allowing for improved temporal scaling of disturbance events. The generally short-term empirical evidence for recovery trajectories of nutrient stocks and partitioning ratios suggests two areas for future research. First, we need to recognize and quantify how disturbance effects can be accreting or depleting, depending on whether their net effect is to increase or decrease ecosystem nutrient stocks. Second, we need to test how altered disturbance frequencies from the present state may be constructive or destructive in their effects on biogeochemical cycling and nutrient availability. Long-term studies, with repeated sampling of soils and vegetation, will be essential in further developing this framework of biogeochemical response to disturbance.This material is based upon work supported by the National Science Foundation under Grant No. DEB-1145815 and 0949420.2016-11-1