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Advanced Exercise Concepts for Exploration

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Liver-specific knockout of arginase-1 leads to a profound phenotype similar to inducible whole body arginase-1 deficiency

Arginase-1 (Arg1) converts arginine to urea and ornithine in the distal step of the urea cycle in liver. We previously generated a tamoxifen-inducible Arg1 deficient mouse model (Arg1-Cre) that disrupts Arg1 expression throughout the whole body and leads to lethality ≈ 2 weeks after gene disruption. Here, we evaluate if liver-selective Arg1 loss is sufficient to recapitulate the phenotype observed in global Arg1 knockout mice, as well as to gauge the effectiveness of gene delivery or hepatocyte transplantation to rescue the phenotype. Liver-selective Arg1 deletion was induced by using an adeno-associated viral (AAV)-thyroxine binding globulin (TBG) promoter-Cre recombinase vector administered to Arg1 "floxed" mice; Arg1(fl/fl) ). An AAV vector expressing an Arg1-enhanced green fluorescent protein (Arg1-eGFP) transgene was used for gene delivery, while intrasplenic injection of wild-type (WT) C57BL/6 hepatocytes after partial hepatectomy was used for cell delivery to "rescue" tamoxifen-treated Arg1-Cre mice. The results indicate that liver-selective loss of Arg1 (> 90% deficient) leads to a phenotype resembling the whole body knockout of Arg1 with lethality ≈ 3 weeks after Cre-induced gene disruption. Delivery of Arg1-eGFP AAV rescues more than half of Arg1 global knockout male mice (survival > 4 months) but a significant proportion still succumb to the enzyme deficiency even though liver expression and enzyme activity of the fusion protein reach levels observed in WT animals. Significant Arg1 enzyme activity from engrafted WT hepatocytes into knockout livers can be achieved but not sufficient for rescuing the lethal phenotype. This raises a conundrum relating to liver-specific expression of Arg1. On the one hand, loss of expression in this organ appears to be both necessary and sufficient to explain the lethal phenotype of the genetic disorder in mice. On the other hand, gene and cell-directed therapies suggest that rescue of extra-hepatic Arg1 expression may also be necessary for disease correction. Further studies are needed in order to illuminate the detailed mechanisms for pathogenesis of Arg1-deficiency

On the Analysis of Phylogenetically Paired Designs

As phylogenetically controlled experimental designs become increasingly common in ecology, the need arises for a standardized statistical treatment of these datasets. Phylogenetically paired designs circumvent the need for resolved phylogenies and have been used to compare species groups, particularly in the areas of invasion biology and adaptation. Despite the widespread use of this approach, the statistical analysis of paired designs has not been critically evaluated. We propose a mixed model approach that includes random effects for pair and species. These random effects introduce a “two-layer” compound symmetry variance structure that captures both the correlations between observations on related species within a pair as well as the correlations between the repeated measurements within species. We conducted a simulation study to assess the effect of model misspecification on Type I and II error rates. We also provide an illustrative example with data containing taxonomically similar species and several outcome variables of interest. We found that a mixed model with species and pair as random effects performed better in these phylogenetically explicit simulations than two commonly used reference models (no or single random effect) by optimizing Type I error rates and power. The proposed mixed model produces acceptable Type I and II error rates despite the absence of a phylogenetic tree. This design can be generalized to a variety of datasets to analyze repeated measurements in clusters of related subjects/species

Isotope effect in quasi-two-dimensional metal-organic antiferromagnets

Although the isotope effect in superconducting materials is well-documented, changes in the magnetic properties of antiferromagnets due to isotopic substitution are seldom discussed and remain poorly understood. This is perhaps surprising given the possible link between the quasi-two-dimensional (Q2D) antiferromagnetic and superconducting phases of the layered cuprates. Here we report the experimental observation of shifts in the N\'{e}el temperature and critical magnetic fields ($\Delta T_{\rm N}/T_{\rm N}\approx 4$; $\Delta B_{\rm c}/B_{\rm c}\approx 4$) in a Q2D organic molecular antiferromagnets on substitution of hydrogen for deuterium. These compounds are characterized by strong hydrogen bonds through which the dominant superexchange is mediated. We evaluate how the in-plane and inter-plane exchange energies evolve as the hydrogens on different ligands are substituted, and suggest a possible mechanism for this effect in terms of the relative exchange efficiency of hydrogen and deuterium bonds

Can Resource-Use Traits Predict Native vs. Exotic Plant Success in Carbon Amended Soils?

Productivity in desert ecosystems is primarily limited by water followed by nitrogen availability. In the deserts of southern California, nitrogen additions have increased invasive annual plant abundance. Similar findings from other ecosystems have led to a general acceptance that invasive plants, especially annual grasses, are nitrophilous. Consequently, reductions of soil nitrogen via carbon amendments have been conducted by many researchers in a variety of ecosystems in order to disproportionately lower invasive species abundance, but with mixed success. Recent studies suggest that resource-use traits may predict the efficacy of such resource manipulations; however, this theory remains largely untested. We report findings from a carbon amendment experiment that utilized two levels of sucrose additions that were aimed at achieving soil carbon to nitrogen ratios of 50:1 and 100:1 in labile sources. Carbon amendments were applied once each year, for three years, corresponding with the first large precipitation event of each wet season. Plant functional traits measured on the three invasive and 11 native herbaceous species that were most common at the study site showed that exotic and native species did not differ in traits associated with nitrogen use. In fact, plant abundance measures such as density, cover, and biomass showed that carbon amendments were capable of decreasing both native and invasive species. We found that early-germinating species were the most impacted by decreased soil nitrogen resulting from amendments. Because invasive annuals typically germinate earlier and exhibit a rapid phenology compared to most natives, these species are expected to be more competitive than native annuals yet more susceptible to early-season carbon amendments. However, desert annual communities can exhibit high interannual variability in species composition and abundance. Therefore, the relative abundance of native and invasive species at the time of application is critical to the success of carbon amendments at our study site. For land management purposes, carbon amendments remain relatively impractical and may only be useful at small scales or in conjunction with other invasive species removal techniques

Fermi-LAT Detection of a Break in the Gamma-Ray Spectrum of the Supernova Remnant Cassiopeia A

We report on observations of the supernova remnant Cassiopeia A in the energy range from 100 MeV to 100 GeV using 44 months of observations from the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. We perform a detailed spectral analysis of this source and report on a low-energy break in the spectrum at $1.72^{+1.35}_{-0.89}$ GeV. By comparing the results with models for the gamma-ray emission, we find that hadronic emission is preferred for the GeV energy range.Comment: 18 pages, 5 figures, 2 tables, to be published in Ap

TARGET: toward a solution for the readout electronics of the Cherenkov Telescope Array

TARGET is an application specific integrated circuit (ASIC) designed to read out signals recorded by the photosensors in cameras of very-high-energy gamma-ray telescopes exploiting the imaging of Cherenkov radiation from atmospheric showers. TARGET capabilities include sampling at a high rate (typically 1 GSample/s), digitization, and triggering on the sum of four adjacent pixels. The small size, large number of channels read out per ASIC (16), low cost per channel, and deep buffer for trigger latency (~16 $\mu$s at 1 GSample/s) make TARGET ideally suited for the readout in systems with a large number of telescopes instrumented with compact photosensors like multi-anode or silicon photomultipliers combined with dual-mirror optics. The possible advantages of such systems are better sensitivity, a larger field of view, and improved angular resolution. The two latest generations of TARGET ASICs, TARGET 5 and TARGET 7, are soon to be used for the first time in two prototypes of small-sized and medium-sized dual-mirror telescopes proposed in the framework of the Cherenkov Telescope Array (CTA) project. In this contribution we report on the performance of the TARGET ASICs and discuss future developments.Comment: 8 pages, 3 figures. In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

TARGET: A Digitizing And Trigger ASIC For The Cherenkov Telescope Array

The future ground-based gamma-ray observatory Cherenkov Telescope Array (CTA) will feature multiple types of imaging atmospheric Cherenkov telescopes, each with thousands of pixels. To be affordable, camera concepts for these telescopes have to feature low cost per channel and at the same time meet the requirements for CTA in order to achieve the desired scientific goals. We present the concept of the TeV Array Readout Electronics with GSa/s sampling and Event Trigger (TARGET) Application Specific Circuit (ASIC), envisaged to be used in the cameras of various CTA telescopes, e.g. the Gamma-ray Cherenkov Telescope (GCT), a proposed 2-Mirror Small-Sized Telescope, and the Schwarzschild-Couder Telescope (SCT), a proposed Medium-Sized Telescope. In the latest version of this readout concept the sampling and trigger parts are split into dedicated ASICs, TARGET C and T5TEA, both providing 16 parallel input channels. TARGET C features a tunable sampling rate (usually 1 GSa/s), a 16k sample deep buffer for each channel and on-demand digitization and transmission of waveforms with typical spans of ~100 ns. The trigger ASIC, T5TEA, provides 4 low voltage differential signal (LVDS) trigger outputs and can generate a pedestal voltage independently for each channel. Trigger signals are generated by T5TEA based on the analog sum of the input in four independent groups of four adjacent channels and compared to a threshold set by the user. Thus, T5TEA generates four LVDS trigger outputs, as well as 16 pedestal voltages fed to TARGET C independently for each channel. We show preliminary results of the characterization and testing of TARGET C and T5TEA.Comment: 6 pages, 8 figures, Proceedings of the 6th International Symposium on High-Energy Gamma-Ray Astronomy (Gamma2016