What should we do about China?

Former US Director of National Intelligence, Admiral Dennis C. Blair examines the changing role of China in the international system and the challenge it poses for policy makers. He highlights in this Centre of Gravity paper how China\u27s concerns about Taiwan are reducing, while its regional assertiveness and economic slowdown provide some caution. This paper presents policy recommendations for Australia and the US to better evaluate and engage China to help secure the Asia-Pacific Region.Executive summary5 years after a major report on US-China relations it’s worth revisiting our assessments. Most judgements remain valid, but some have changed significantly. Taiwan has moved from a primary issue to second order, though not forgotten. China’s regional assertiveness is concerning and should be examined closely. China’s economic development model has run its course; Beijing needs to provide leadership to usher in reform.Policy recommendationsAustralia and the USA should focus on a blended policy of cooperation with China, along with an insistence on international norms, and maintenance of alliance and military strength. Regular evaluations of China’s shifting capacity and interests, to identify what issues are of rising or declining significance for Beijing will be needed to be effective in engaging China and building a better future for the region

What Should We do About China?

Former US Director of National Intelligence, Admiral Dennis C. Blair examines the changing role of China in the international system and the challenge it poses for policy makers. He highlights in this Centre of Gravity paper how China's concerns about Taiwan are reducing, while its regional assertiveness and economic slowdown provide some caution. This paper presents policy recommendations for Australia and the US to better evaluate and engage China to help secure the Asia-Pacific Regio

Bonded Cumomer Analysis of Human Melanoma Metabolism Monitored by 13C NMR Spectroscopy of Perfused Tumor Cells.

A network model for the determination of tumor metabolic fluxes from (13)C NMR kinetic isotopomer data has been developed and validated with perfused human DB-1 melanoma cells carrying the BRAF V600E mutation, which promotes oxidative metabolism. The model generated in the bonded cumomer formalism describes key pathways of tumor intermediary metabolism and yields dynamic curves for positional isotopic enrichment and spin-spin multiplets. Cells attached to microcarrier beads were perfused with 26 mm [1,6-(13)C2]glucose under normoxic conditions at 37 °C and monitored by (13)C NMR spectroscopy. Excellent agreement between model-predicted and experimentally measured values of the rates of oxygen and glucose consumption, lactate production, and glutamate pool size validated the model. ATP production by glycolytic and oxidative metabolism were compared under hyperglycemic normoxic conditions; 51% of the energy came from oxidative phosphorylation and 49% came from glycolysis. Even though the rate of glutamine uptake was ∼50% of the tricarboxylic acid cycle flux, the rate of ATP production from glutamine was essentially zero (no glutaminolysis). De novo fatty acid production was ∼6% of the tricarboxylic acid cycle flux. The oxidative pentose phosphate pathway flux was 3.6% of glycolysis, and three non-oxidative pentose phosphate pathway exchange fluxes were calculated. Mass spectrometry was then used to compare fluxes through various pathways under hyperglycemic (26 mm) and euglycemic (5 mm) conditions. Under euglycemic conditions glutamine uptake doubled, but ATP production from glutamine did not significantly change. A new parameter measuring the Warburg effect (the ratio of lactate production flux to pyruvate influx through the mitochondrial pyruvate carrier) was calculated to be 21, close to upper limit of oxidative metabolism

Agricultural Pesticide Use and Risk of t(14;18)-Defined Subtypes of Non-Hodgkin Lymphoma

Pesticides have been specifically associated with the t(14;18)(q32;q21) chromosomal translocation. To investigate whether the association between pesticides and risk of non-Hodgkin lymphoma (NHL) differs for molecular subtypes of NHL defined by t(14; 18) status, we obtained 175 tumor blocks from case subjects in a population-based case-control study conducted in Nebraska between 1983 and 1986. The t(14;18) was determined by interphase fluorescence in situ hybridization in 172 of 175 tumor blocks. We compared exposures to insecticides, herbicides, fungicides, and fumigants in 65 t(14;18)-positive and 107 t(14;18)-negative case subjects with those among 1432 control subjects. Multivariate polytomous logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared with farmers who never used pesticides, the risk of t(14;18)-positive NHL was significantly elevated among farmers who used animal insecticides (OR = 2.6; 95%CI, 1.0-6.9), crop insecticides (OR = 3.0; 95% CI, 1.1-8.2), herbicides (OR = 2.9; 95% CI, 1.1-7.9), and fumigants (OR = 5.0; 95% CI, 1.7-14.5). None of these pesticides were associated with t(14;18)-negative NHL. The risk of t(14;18)-positive NHL associated with insecticides and herbicides increased with longer duration of use. We conclude that insecticides, herbicides, and fumigants were associated with risk of t(14;18)-positive NHL but not t(14;18)-negative NHL. These results suggest that defining subsets of NHL according to t(14;18) status is a useful approach for etiologic research. (Blood. 2006; 108:1363-1369

Optical Structure and Proper-Motion Age of the Oxygen-rich Supernova Remnant 1E 0102-7219 in the Small Magellanic Cloud

We present new optical emission-line images of the young SNR 1E 0102-7219 (E0102) in the SMC obtained with the HST Advanced Camera for Surveys (ACS). E0102 is a member of the oxygen-rich class of SNRs showing strong oxygen, neon , and other metal-line emissions in its optical and X-ray spectra, and an absence of H and He. The progenitor of E0102 may have been a Wolf-Rayet star that underwent considerable mass loss prior to exploding as a Type Ib/c or IIL/b SN. The ejecta in this SNR are fast-moving (V > 1000 km/s) and emit as they are compressed and heated in the reverse shock. In 2003, we obtained optical [O III], H-alpha, and continuum images with the ACS Wide Field Camera. The [O III] image captures the full velocity range of the ejecta, and shows considerable high-velocity emission projected in the middle of the SNR that was Doppler-shifted out of the narrow F502N bandpass of a previous Wide Field and Planetary Camera 2 image from 1995. Using these two epochs separated by ~8.5 years, we measure the transverse expansion of the ejecta around the outer rim in this SNR for the first time at visible wavelengths. From proper-motion measurements of 12 ejecta filaments, we estimate a mean expansion velocity for the bright ejecta of ~2000 km/s and an inferred kinematic age for the SNR of \~2050 +/- 600 years. The age we derive from HST data is about twice that inferred by Hughes et al.(2000) from X-ray data, though our 1-sigma error bars overlap. Our proper-motion age is consistent with an independent optical kinematic age derived by Eriksen et al.(2003) using spatially resolved [O III] radial-velocity data. We derive an expansion center that lies very close to X-ray and radio hotspots, which could indicate the presence of a compact remnant (neutron star or black hole).Comment: 28 pages, 8 figures. Accepted to the Astrophysical Journal, to appear in 20 April 2006 issue. Full resolution figures are posted at: http://stevenf.asu.edu/figure

(13)C MRS and LC-MS Flux Analysis of Tumor Intermediary Metabolism.

We present the first validated metabolic network model for analysis of flux through key pathways of tumor intermediary metabolism, including glycolysis, the oxidative and non-oxidative arms of the pentose pyrophosphate shunt, the TCA cycle as well as its anaplerotic pathways, pyruvate-malate shuttling, glutaminolysis, and fatty acid biosynthesis and oxidation. The model that is called Bonded Cumomer Analysis for application to (13)C magnetic resonance spectroscopy ((13)C MRS) data and Fragmented Cumomer Analysis for mass spectrometric data is a refined and efficient form of isotopomer analysis that can readily be expanded to incorporate glycogen, phospholipid, and other pathways thereby encompassing all the key pathways of tumor intermediary metabolism. Validation was achieved by demonstrating agreement of experimental measurements of the metabolic rates of oxygen consumption, glucose consumption, lactate production, and glutamate pool size with independent measurements of these parameters in cultured human DB-1 melanoma cells. These cumomer models have been applied to studies of DB-1 melanoma and DLCL2 human diffuse large B-cell lymphoma cells in culture and as xenografts in nude mice at 9.4 T. The latter studies demonstrate the potential translation of these methods to in situ studies of human tumor metabolism by MRS with stable (13)C isotopically labeled substrates on instruments operating at high magnetic fields (≥7 T). The melanoma studies indicate that this tumor line obtains 51% of its ATP by mitochondrial metabolism and 49% by glycolytic metabolism under both euglycemic (5 mM glucose) and hyperglycemic conditions (26 mM glucose). While a high level of glutamine uptake is detected corresponding to ~50% of TCA cycle flux under hyperglycemic conditions, and ~100% of TCA cycle flux under euglycemic conditions, glutaminolysis flux and its contributions to ATP synthesis were very small. Studies of human lymphoma cells demonstrated that inhibition of mammalian target of rapamycin (mTOR) signaling produced changes in flux through the glycolytic, pentose shunt, and TCA cycle pathways that were evident within 8 h of treatment and increased at 24 and 48 h. Lactate was demonstrated to be a suitable biomarker of mTOR inhibition that could readily be monitored by (1)H MRS and perhaps also by FDG-PET and hyperpolarized (13)C MRS methods

SMASHing the LMC: A Tidally-induced Warp in the Outer LMC and a Large-scale Reddening Map

We present a study of the three-dimensional (3D) structure of the Large Magellanic Cloud (LMC) using ~2.2 million red clump (RC) stars selected from the Survey of the MAgellanic Stellar History. To correct for line-of-sight dust extinction, the intrinsic RC color and magnitude and their radial dependence are carefully measured by using internal nearly dust-free regions. These are then used to construct an accurate 2D reddening map (165 square degrees with ~10 arcmin resolution) of the LMC disk and the 3D spatial distribution of RC stars. An inclined disk model is fit to the 2D distance map yielding a best-fit inclination angle i = 25.86(+0.73,-1.39) degrees with random errors of +\-0.19 degrees and line-of-nodes position angle theta = 149.23(+6.43,-8.35) degrees with random errors of +/-0.49 degrees. These angles vary with galactic radius, indicating that the LMC disk is warped and twisted likely due to the repeated tidal interactions with the Small Magellanic Cloud (SMC). For the first time, our data reveal a significant warp in the southwestern part of the outer disk starting at rho ~ 7 degrees that departs from the defined LMC plane up to ~4 kpc toward the SMC, suggesting that it originated from a strong interaction with the SMC. In addition, the inner disk encompassing the off-centered bar appears to be tilted up to 5-15 degrees relative to the rest of the LMC disk. These findings on the outer warp and the tilted bar are consistent with the predictions from the Besla et al. simulation of a recent direct collision with the SMC.Comment: 25 pages, 15 figures, published in Ap

Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

The Cosmic Origins Spectrograph

The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F(sub lambda) approximates 1.0 X 10(exp -14) ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy