Fast-ignition design transport studies: realistic electron source, integrated PIC-hydrodynamics, imposed magnetic fields

Transport modeling of idealized, cone-guided fast ignition targets indicates the severe challenge posed by fast-electron source divergence. The hybrid particle-in-cell [PIC] code Zuma is run in tandem with the radiation-hydrodynamics code Hydra to model fast-electron propagation, fuel heating, and thermonuclear burn. The fast electron source is based on a 3D explicit-PIC laser-plasma simulation with the PSC code. This shows a quasi two-temperature energy spectrum, and a divergent angle spectrum (average velocity-space polar angle of 52 degrees). Transport simulations with the PIC-based divergence do not ignite for > 1 MJ of fast-electron energy, for a modest 70 micron standoff distance from fast-electron injection to the dense fuel. However, artificially collimating the source gives an ignition energy of 132 kJ. To mitigate the divergence, we consider imposed axial magnetic fields. Uniform fields ~50 MG are sufficient to recover the artificially collimated ignition energy. Experiments at the Omega laser facility have generated fields of this magnitude by imploding a capsule in seed fields of 50-100 kG. Such imploded fields are however more compressed in the transport region than in the laser absorption region. When fast electrons encounter increasing field strength, magnetic mirroring can reflect a substantial fraction of them and reduce coupling to the fuel. A hollow magnetic pipe, which peaks at a finite radius, is presented as one field configuration which circumvents mirroring.Comment: 16 pages, 17 figures, submitted to Phys. Plasma

Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS)

Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in endâ stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 à  108 renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cellâ treated sheep retained neutrophil oxidative activity better than shamâ treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140038/1/term2206.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140038/2/term2206_am.pd

Planets in Stellar Clusters Extensive Search. II. Discovery of 57 Variables in the Cluster NGC 2158 with Millimagnitude Image Subtraction Photometry

We have undertaken a long-term project, Planets in Stellar Clusters Extensive Search (PISCES), to search for transiting planets in open clusters. NGC 2158 is one of the targets we have chosen -- an intermediate age, populous, rather metal poor cluster. In this paper we present the results of a search for variable stars in the data from the first season of monitoring at the FLWO 1.2 m telescope. This is the first variability search ever conducted in this cluster. We present a catalog of 57 variable stars, most with low amplitude variability. Among the variables is a cataclysmic variable (CV) which underwent a 2.5 mag outburst. If it is a member of NGC 2158, this would be the fourth CV known in an open cluster. We have also found five delta Scuti stars, three of which we have two or more detectable modes of pulsation. Of the 57 variables discovered, 28 have R-band amplitudes of 5% or below. Six of those vary at or below the 2% level, including one with 0.08% variability.Comment: 13 pages LaTeX, including 8 figures and 4 tables, submitted to Astronomical Journal. Version with full resolution figures available through ftp at ftp://cfa-ftp.harvard.edu/pub/bmochejs/PISCES/papers/2_N2158

Translation of immunomodulatory therapy to treat chronic heart failure: Preclinical studies to first in human

BACKGROUND: Inflammation has been associated with progression and complications of chronic heart failure (HF) but no effective therapy has yet been identified to treat this dysregulated immunologic state. The selective cytopheretic device (SCD) provides extracorporeal autologous cell processing to lessen the burden of inflammatory activity of circulating leukocytes of the innate immunologic system. AIM: The objective of this study was to evaluate the effects of the SCD as an extracorporeal immunomodulatory device on the immune dysregulated state of HF. HF. METHODS AND RESULTS: SCD treatment in a canine model of systolic HF or HF with reduced ejection fraction (HFrEF) diminished leukocyte inflammatory activity and enhanced cardiac performance as measured by left ventricular (LV) ejection fraction and stroke volume (SV) up to 4 weeks after treatment initiation. Translation of these observations in first in human, proof of concept clinical study was evaluated in a patient with severe HFrEFHFrEF ineligible for cardiac transplantation or LV LV assist device (LVAD) due to renal insufficiency and right ventricular dysfunction. Six hour SCD treatments over 6 consecutive days resulted in selective removal of inflammatory neutrophils and monocytes and reduction in key plasma cytokines, including tumor necrosis factor-alpha (TNF-α),), interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1. These immunologic changes were associated with significant improvements in cardiac power output, right ventricular stroke work index, cardiac index and LVSV index…. Stabilization of renal function with progressive volume removal permitted successful LVAD implantation. CONCLUSION: This translational research study demonstrates a promising immunomodulatory approach to improve cardiac performance in HFrEFHFrEF and supports the important role of inflammation in the progression of HFHF

Common Genetic Variants Found in HLA and KIR Immune Genes in Autism Spectrum Disorder

The “common variant—common disease” hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased vs. matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the “common variant—common disease” hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics. Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14 bp-indel) frequencies are significantly increased by more than 5% over control populations (Table 2). The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2). Three activating KIR genes: 3DS1, 2DS1, and 2DS2 have increased frequencies of 15, 22, and 14% in autism populations, respectively. There is a 6% increase in total activating KIR genes in autism over control subjects. And, more importantly there is a 12% increase in activating KIR genes and their cognate HLA alleles over control populations (Torres et al., 2012a). These data suggest the interaction of HLA ligand/KIR receptor pairs encoded on two different chromosomes is more significant as a ligand/receptor complex than separately in autism

Exploring the influence of ancient and historic megaherbivore extirpations on the global methane budget

Globally, large-bodied wild mammals are in peril. Because “megamammals” have a disproportionate influence on vegetation, trophic interactions, and ecosystem function, declining populations are of considerable conservation concern. However, this is not new; trophic downgrading occurred in the past, including the African rinderpest epizootic of the 1890s, the massive Great Plains bison kill-off in the 1860s, and the terminal Pleistocene extinction of megafauna. Examining the consequences of these earlier events yields insights into contemporary ecosystem function. Here, we focus on changes inmethane emissions, produced as a byproduct of enteric fermentation by herbivores. Although methane is ∼200 times less abundant than carbon dioxide in the atmosphere, the greater efficiency of methane in trapping radiation leads to a significant role in radiative forcing of climate. Using global datasets of late Quaternary mammals, domestic livestock, and human population from the United Nations as well as literature sources, we develop a series of allometric regressions relating mammal body mass to population density and CH4 production, which allows estimation of methane production by wild and domestic herbivores for each historic or ancient time period. We find the extirpation ofmegaherbivores reduced global enteric emissions between 2.2–69.6 Tg CH4 y−1 during the various time periods, representing a decrease of 0.8–34.8% of the overall inputs to tropospheric input. Our analyses suggest that large-bodied mammals have a greater influence on methane emissions than previously appreciated and, further, that changes in the source pool from herbivores can influence global biogeochemical cycles and, potentially, climate

A Biomimetic Membrane Device That Modulates the Excessive Inflammatory Response to Sepsis

OBJECTIVE: Septic shock has a clinical mortality rate approaching fifty percent. The major clinical manifestations of sepsis are due to the dysregulation of the host's response to infection rather than the direct consequences of the invading pathogen. Central to this initial immunologic response is the activation of leukocytes and microvascular endothelium resulting in cardiovascular instability, lung injury and renal dysfunction. Due to the primary role of leukocyte activation in the sepsis syndrome, a synthetic biomimetic membrane, called a selective cytopheretic device (SCD), was developed to bind activated leukocytes. The incorporation of the SCD along an extracorporeal blood circuit coupled with regional anticoagulation with citrate to lower blood ionized calcium was devised to modulate leukocyte activation in sepsis. DESIGN: Laboratory investigation. SETTING: University of Michigan Medical School. SUBJECTS: Pigs weighing 30-35 kg. INTERVENTIONS: To assess the effect of the SCD in septic shock, pigs were administered 30×10(10) bacteria/kg body weight of Escherichia coli into the peritoneal cavity and within 1 hr were immediately placed in an extracorporeal circuit containing SCD. MEASUREMENTS AND MAIN RESULTS: In this animal model, the SCD with citrate compared to control groups without the SCD or with heparin anticoagulation ameliorated the cardiovascular instability and lung sequestration of activated leukocytes, reduced renal dysfunction and improved survival time compared to various control groups. This effect was associated with minimal elevations of systemic circulating neutrophil activation. CONCLUSIONS: These preclinical studies along with two favorable exploratory clinical trials form the basis of an FDA-approved investigational device exemption for a pivotal multicenter, randomized control trial currently underway

Effect of Thermoelectric Cooling in Nanoscale Junctions

We propose a thermoelectric cooling device based on an atomic-sized junction. Using first-principles approaches, we investigate the working conditions and the coefficient of performance (COP) of an atomic-scale electronic refrigerator where the effects of phonon's thermal current and local heating are included. It is observed that the functioning of the thermoelectric nano-refrigerator is restricted to a narrow range of driving voltages. Compared with the bulk thermoelectric system with the overwhelmingly irreversible Joule heating, the 4-Al atomic refrigerator has a higher efficiency than a bulk thermoelectric refrigerator with the same $ZT$ due to suppressed local heating via the quasi-ballistic electron transport and small driving voltages. Quantum nature due to the size minimization offered by atomic-level control of properties facilitates electron cooling beyond the expectation of the conventional thermoelectric device theory.Comment: 8 figure

Physiological consequences of abnormal connectivity in a developmental epilepsy

Objective Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods We employed transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recording in 8 patients with epilepsy from periventricular nodular heterotopia and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in 1 subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions