Simulations of MHD Instabilities in Intracluster Medium Including Anisotropic Thermal Conduction

We perform a suite of simulations of cooling cores in clusters of galaxies in order to investigate the effect of the recently discovered heat flux buoyancy instability (HBI) on the evolution of cores. Our models follow the 3-dimensional magnetohydrodynamics (MHD) of cooling cluster cores and capture the effects of anisotropic heat conduction along the lines of magnetic field, but do not account for the cosmological setting of clusters or the presence of AGN. Our model clusters can be divided into three groups according to their final thermodynamical state: catastrophically collapsing cores, isothermal cores, and an intermediate group whose final state is determined by the initial configuration of magnetic field. Modeled cores that are reminiscent of real cluster cores show evolution towards thermal collapse on a time scale which is prolonged by a factor of ~2-10 compared with the zero-conduction cases. The principal effect of the HBI is to re-orient field lines to be perpendicular to the temperature gradient. Once the field has been wrapped up onto spherical surfaces surrounding the core, the core is insulated from further conductive heating (with the effective thermal conduction suppressed to less than 1/100th of the Spitzer value) and proceeds to collapse. We speculate that, in real clusters, the central AGN and possibly mergers play the role of "stirrers," periodically disrupting the azimuthal field structure and allowing thermal conduction to sporadically heat the core.Comment: 16 pages, 3 tables, 17 figures, accepted to ApJ with minor revisions, to appear in Volume 704, Oct 20, 2009 issu

Summary Data for Cross-Shore Transects (Winter 2016-Summer 2020) - Humboldt Coastal Resiliency Project and Climate Ready Project

Sea level rise and/or extreme events are capable of causing excessive erosion on the beaches and foredunes that line the outer edges of the barriers enclosing Humboldt Bay and the Eel River delta within the Eureka littoral cell. Erosion of these protective barriers threatens the natural and cultural resources and infrastructure behind them in two significant estuaries. A major goal of the Climate Ready Project and the Humboldt Coastal Resilience Project was to quantify present day beach-dune morphodynamics, which could then be used to model the impacts of sea level rise and extreme events. For this purpose, a total of 73 cross-shore transects were established along the littoral cell. Elevation and vegetation data collected on transects will be used in a quantitative model to predict beach, dune and barrier responses to sea level rise and extreme events. The purpose of this report is to present raw data in the form of graphs of elevation change along transects as the basis of qualitative observations of response during the period of data collection, 2016-2020. The primary audience is property owners within the study site. Conclusions of this report are based on qualitative analysis and may change when modeling is complete

The Impact of Local Power Balance and Link Reliability on Blackout Risk in Heterogeneous Power Transmission Grids

Many critical infrastructures such as the power transmission grid are heterogeneous both in their basic structure and in some of their underlying characteristics, This heterogeneity can be good for system robustness if it reduces the spread of failures or bad if it adds risk or vulnerability to the system. In this paper we investigate the effect of heterogeneity in the strength of the links between parts of the system network structures, as well as the balance of local generation and demand, on the robustness of the power transmission grid using the OPA complex system model of the power transmission system. It is found that increasing or decreasing the reliability of the links between parts of the grid changes the likelihood of different size failures with neither being optimal for all sizes. Furthermore, imbalances between load and generation in the local regions further degrades the system reliability

Association of N-terminal pro-brain natriuretic peptide with cognitive function and depression in elderly people with type 2 diabetes

<p>Background: Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).</p> <p>Methodology and Principal Findings: Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).</p> <p>Conclusion: Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.</p&gt

The Intermediate Luminosity Optical Transient SN 2010da: The Progenitor, Eruption and Aftermath of a Peculiar Supergiant High-mass X-ray Binary

We present optical spectroscopy, ultraviolet to infrared imaging and X-ray observations of the intermediate luminosity optical transient (ILOT) SN 2010da in NGC 300 (d=1.86 Mpc) spanning from -6 to +6 years relative to the time of outburst in 2010. Based on the light curve and multi-epoch SEDs of SN 2010da, we conclude that the progenitor of SN 2010da is a ~10-12 Msol yellow supergiant possibly transitioning into a blue loop phase. During outburst, SN 2010da had a peak absolute magnitude of M<-10.4 mag, dimmer than other ILOTs and supernova impostors. We detect multi-component hydrogen Balmer, Paschen, and Ca II emission lines in our high-resolution spectra, which indicate a dusty and complex circumstellar environment. Since the 2010 eruption, the star has brightened by a factor of ~5 and remains highly variable in the optical. Furthermore, we detect SN 2010da in archival Swift and Chandra observations as an ultraluminous X-ray source (L~6x10^{39} erg/s). We additionally attribute He II 4686 Angstrom and coronal Fe emission lines in addition to a steady X-ray luminosity of ~10^{37} erg/s to the presence of a compact companion.Comment: published; updated citations and other minor edit

Differential effects of oilseed supplements on methane production and milk fatty acid concentrations in dairy cows

It is known that supplementing dairy cow diets with full-fat oilseeds can be used as a strategy to mitigate methane emissions, through their action on rumen fermentation. However, direct comparisons of the effect of different oil sources are very few, as are studies implementing supplementation levels that reflect what is commonly fed on commercial farms. The objective was to investigate the effect of feeding different forms of supplemental plant oils on both methane emissions and milk fatty acid (FA) profile. Four multiparous, Holstein-Friesian cows in mid-lactation were randomly allocated to one of four treatment diets in a 4 x 4 Latin square design with 28-day periods. Diets were fed as a TMR with a 50:50 forage:concentrate ratio (dry matter, DM basis) with the forage consisting of 75:25 maize silage:grass silage (DM). Dietary treatments were a control diet containing no supplemental fat, and three treatment diets containing extruded linseed (EL), calcium salts of palm and linseed oil (CPLO) or milled rapeseed (MR) formulated to provide each cow with an estimated 500 g additional oil/d (22 g oil/kg diet DM). Dry matter intake (DMI), milk yield, milk composition and methane production were measured at the end of each experimental period when cows were housed in respiration chambers for 4 days. There was no effect of treatment diet on DMI or milk protein or lactose concentration, but oilseed-based supplements increased milk yield compared with the control diet and milk fat concentration relative to control was reduced by 4 g/kg by supplemental EL. Feeding CPLO reduced methane production, and both linseed-based supplements decreased methane yield (by 1.8 L/kg DMI) and intensity (by 2.7 L/kg milk yield) compared with the control diet, but feeding MR had no effect on methane emission. All the fat supplements decreased milk total saturated fatty acid (SFA) concentration compared with the control, and SFA were replaced with mainly cis-9 18:1 but also trans FA (and in the case of EL and CPLO there were increases in polyunsaturated FA concentration). Supplementing dairy cow diets with these oilseed-based preparations affected milk FA profile and increased milk yield. However, only the linseed-based supplements reduced methane production, yield, or intensity, whilst feeding MR had no effect

HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer.

BackgroundHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab - however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody-liposomal doxorubicin conjugate that specifically targets HER2-overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations.Methods/designHERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab.DiscussionThe HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage.Trial registrationClinicaltrials.gov identifier: NCT02213744 . Registration date: 06AUG2014

FINITE H-DIMENSION DOES NOT IMPLY EXPRESSIVE COMPLETENESS

Accepted versio

Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death.

Glutamate is the dominant excitatory neurotransmitter in the brain, but under conditions of metabolic stress it can accumulate to excitotoxic levels. Although pharmacologic modulation of excitatory amino acid receptors is well studied, minimal consideration has been given to targeting mitochondrial glutamate metabolism to control neurotransmitter levels. Here we demonstrate that chemical inhibition of the mitochondrial pyruvate carrier (MPC) protects primary cortical neurons from excitotoxic death. Reductions in mitochondrial pyruvate uptake do not compromise cellular energy metabolism, suggesting neuronal metabolic flexibility. Rather, MPC inhibition rewires mitochondrial substrate metabolism to preferentially increase reliance on glutamate to fuel energetics and anaplerosis. Mobilizing the neuronal glutamate pool for oxidation decreases the quantity of glutamate released upon depolarization and, in turn, limits the positive-feedback cascade of excitotoxic neuronal injury. The finding links mitochondrial pyruvate metabolism to glutamatergic neurotransmission and establishes the MPC as a therapeutic target to treat neurodegenerative diseases characterized by excitotoxicity

An integrated carbon and oxygen isotope approach to reconstructing past environmental variability in the northeast Atlantic Ocean

The combined influence of temperature and the isotopic composition of the seawater (δ18Ow) often precludes the use of oxygen isotope (δ18O) records, derived from marine carbonates, to reconstruct absolute seawater temperatures, without the application of an independent δ18Ow proxy. Here we investigate the application of carbon isotope records (δ13Cshell), derived from the long-lived marine bivalve Glycymeris glycymeris, as a proxy for δ18Ow variability. Our analyses indicate G. glycymeris δ13Cshell data derived from growth increments >20 years of age contain strong ontogenetic trends (−0.013‰ yr−1, R = 0.98, P < 0.001, N = 51). These analyses demonstrate that, coupled with the ontogenetic trends, 54% of the variability in G. glycymeris δ13Cshell records can be explained by a combination of the marine Suess effect and physical (salinity and riverine input) and biological processes (primary production). The application of these δ13Cshell data in conjunction with co-registered δ18Oshell and growth increment width series, each of which have been shown to be sensitive to seawater temperature and primary productivity respectively, can therefore provide new insights into past environmental variability and help constrain uncertainties on reconstructions of past seawater temperature variability