The growth of bilateralism

One of the most notable international economic events over the past 20 years has been the proliferation of bilateral free trade agreements (FTAs). Bilateral agreements account for 80 percent of all agreements notified to the WTO, 94 percent of those signed or under negotiation, and currently 100 percent of those at the proposal stage. Some have argued that the growth of bilateralism is attributable to governments having pursued a policy of “competitive liberalization" - implementing bilateral FTAs to offset potential trade diversion caused by FTAs of “third-country-pairs" - but the growth of bilateralism can also be attributed potentially to “tariff complementarity" - the incentive for FTA members to reduce their external tariffs on nonmembers. Guided by new comparative statics from the numerical general equilibrium monopolistic competition model of FTA economic determinants in Baier and Bergstrand (2004), we augment their parsimonious logit (and probit) model of the economic determinants of bilateral FTAs to incorporate theory-motivated indexes to examine the influence of existing memberships on subsequent FTA formations. The model can predict correctly 90 percent of the bilateral FTAs within five years of their formation, while still predicting “No-FTA" correctly in 90 percent of the observations when no FTA exists, using a sample of over 350,000 observations for pairings of 146 countries from 1960-2005. Even imposing the higher correct prediction rate of “No-FTA" of 97 percent in Baier and Bergstrand (2004), the parsimonious model still predicts correctly 75 percent of these rare FTA events; only 3 percent of the observations reflect a country-pair having an FTA in any year. The results suggest that - while evidence supports that “competitive liberalization" is a force for bilateralism - the effect on the likelihood a pair of countries forming an FTA of the pair's own FTAs with other countries (i.e., tariff complementarity) is likely just as important as the effect of third-country-pairs' FTAs (i.e., competitive liberalization) for the growth of bilateralism

Novel BRAF Alteration in a Sporadic Pilocytic Astrocytoma

Pilocytic astrocytoma (PA) is the most frequently encountered glial tumor (glioma or astrocytoma) in children. Recent studies have identified alterations in the BRAF serine/threonine kinase gene as the likely causative mutation in these childhood brain tumors. The majority of these genetic changes involve chromosome 7q34 tandem duplication, resulting in aberrant BRAF fusion transcripts. In this paper, we describe a novel KIAA1549:BRAF fusion transcript in a sporadic PA tumor associated with increased ERK activation and review the spectrum of BRAF genetic alterations in this common pediatric low-grade central nervous system neoplasm

Necrotizing pancreatitis: A review for the acute care surgeon

BACKGROUND: Necrotizing pancreatitis is a common condition with high mortality; the acute care surgeon is frequently consulted for management recommendations. Furthermore, there has been substantial change in the timing, approach, and frequency of surgical intervention for this group of patients. METHODS: In this article we summarize key clinical and research developments regarding necrotizing pancreatitis, including current recommendations for treatment of patients requiring intensive care and those with common complications. Articles from all years were considered to provide proper historical context, and most recent management recommendations are identified. RESULTS: Epidemiology, diagnosis, treatment in the acute phase, and complications (both short-term and long-term) are discussed. Images of surgical interventions are included from our institutional experience. CONCLUSION: Necrotizing pancreatitis management remains heavily based on clinical judgement, although technological advances and clinical trials have made decision making more straightforward

Ecological condition of coastal ocean waters along the U.S. Mid-Atlantic Bight: 2006

In May 2006, the NOAA National Ocean Service (NOS), in conjunction with the EPA National Health and Environmental Effects Laboratory (NHEERL), conducted an assessment of the status of ecological condition of soft-bottom habitat and overlying waters throughout the mid-Atlantic Bight (MAB) portion of the eastern U.S. continental shelf. The study area encompassed the region from Cape Cod, MA and Nantucket Shoals in the northeast to Cape Hatteras in the south, and was defined using a one nautical mile buffer of the shoreline extended seaward to the shelf break (~100-m depth contour). A total of 50 stations were targeted for sampling using standard methods and indicators applied in prior NOAA coastal studies and EPA’s Environmental Monitoring and Assessment Program (EMAP) and National Coastal Assessment (NCA). A key feature adopted from these studies was the incorporation of a random probabilistic sampling design. Such a design provides a basis for making unbiased statistical estimates of the spatial extent of ecological condition relative to various measured indicators and corresponding thresholds of concern. Indicators included multiple measures of water quality, sediment quality, and biological condition (benthic fauna). Through coordination with the NOAA Fisheries Service/Northeast Fisheries Science Center (NFS/NEFSC), samples of summer flounder (Paralichthys dentatus) also were obtained from 30 winter 2007 bottom-trawl survey stations in overlapping portions of the study area and used for analysis of chemical-contaminant body burdens

Linked Autonomous Interplanetary Satellite Orbit Navigation

A navigation technology known as LiAISON (Linked Autonomous Interplanetary Satellite Orbit Navigation) has been known to produce very impressive navigation results for scenarios involving two or more cooperative satellites near the Moon, such that at least one satellite must be in an orbit significantly perturbed by the Earth, such as a lunar halo orbit. The two (or more) satellites track each other using satellite-to-satellite range and/or range-rate measurements. These relative measurements yield absolute orbit navigation when one of the satellites is in a lunar halo orbit, or the like. The geometry between a lunar halo orbiter and a GEO satellite continuously changes, which dramatically improves the information content of a satellite-to-satellite tracking signal. The geometrical variations include significant out-of-plane shifts, as well as inplane shifts. Further, the GEO satellite is almost continuously in view of a lunar halo orbiter. High-fidelity simulations demonstrate that LiAISON technology improves the navigation of GEO orbiters by an order of magnitude, relative to standard ground tracking. If a GEO satellite is navigated using LiAISON- only tracking measurements, its position is typically known to better than 10 meters. If LiAISON measurements are combined with simple radiometric ground observations, then the satellite s position is typically known to better than 3 meters, which is substantially better than the current state of GEO navigation. There are two features of LiAISON that are novel and advantageous compared with conventional satellite navigation. First, ordinary satellite-to-satellite tracking data only provides relative navigation of each satellite. The novelty is the placement of one navigation satellite in an orbit that is significantly perturbed by both the Earth and the Moon. A navigation satellite can track other satellites elsewhere in the Earth-Moon system and acquire knowledge about both satellites absolute positions and velocities, as well as relative positions and velocities in space. The second novelty is that ordinarily one requires many satellites in order to achieve full navigation of any given customer s position and velocity over time. With LiAISON navigation, only a single navigation satellite is needed, provided that the satellite is significantly affected by the gravity of the Earth and the Moon. That single satellite can track another satellite elsewhere in the Earth- Moon system and obtain absolute knowledge of both satellites states

Novel chemical library screen identifies naturally occurring plant products that specifically disrupt glioblastoma-endothelial cell interactions

Tumor growth is not solely a consequence of autonomous tumor cell properties. Rather, tumor cells act upon and are acted upon by their microenvironment. It is tumor tissue biology that ultimately determines tumor growth. Thus, we developed a compound library screen for agents that could block essential tumor-promoting effects of the glioblastoma (GBM) perivascular stem cell niche (PVN). We modeled the PVN with three-dimensional primary cultures of human brain microvascular endothelial cells in Matrigel. We previously demonstrated stimulated growth of GBM cells in this PVN model and used this to assay PVN function. We screened the Microsource Spectrum Collection library for drugs that specifically blocked PVN function, without any direct effect on GBM cells themselves. Three candidate PVN-disrupting agents, Iridin, Tigogenin and Triacetylresveratrol (TAR), were identified and evaluated in secondary in vitro screens against a panel of primary GBM isolates as well as in two different in vivo intracranial models. Iridin and TAR significantly inhibited intracranial tumor growth and prolonged survival in these mouse models. Together these data identify Iridin and TAR as drugs with novel GBM tissue disrupting effects and validate the importance of preclinical screens designed to address tumor tissue function rather than the mechanisms of autonomous tumor cell growth

SN2012ab: A Peculiar Type IIn Supernova with Aspherical Circumstellar Material

We present photometry, spectra, and spectropolarimetry of supernova (SN) 2012ab, mostly obtained over the course of $\sim 300$ days after discovery. SN 2012ab was a Type IIn (SN IIn) event discovered near the nucleus of spiral galaxy 2MASXJ12224762+0536247. While its light curve resembles that of SN 1998S, its spectral evolution does not. We see indications of CSM interaction in the strong intermediate-width emission features, the high luminosity (peak at absolute magnitude $M=-19.5$), and the lack of broad absorption features in the spectrum. The H$\alpha$ emission undergoes a peculiar transition. At early times it shows a broad blue emission wing out to $-14{,}000$ km $\mathrm{s^{-1}}$ and a truncated red wing. Then at late times ($>$ 100$\,$days) it shows a truncated blue wing and a very broad red emission wing out to roughly $+20{,}000$ km $\mathrm{s^{-1}}$. This late-time broad red wing probably arises in the reverse shock. Spectra also show an asymmetric intermediate-width H$\alpha$ component with stronger emission on the red side at late times. The evolution of the asymmetric profiles requires a density structure in the distant CSM that is highly aspherical. Our spectropolarimetric data also suggest asphericity with a strong continuum polarization of $\sim 1-3$% and depolarization in the H$\alpha$ line, indicating asphericity in the CSM at a level comparable to that in other SNe IIn. We estimate a mass-loss rate of $\dot{M} = 0.050\, {\rm M}_{\odot}\,\mathrm{yr^{-1}}$ for $v_{\rm pre} = 100$$\,$km$\,$$\mathrm{s^{-1}}$ extending back at least 75$\,$yr prior to the SN. The strong departure from axisymmetry in the CSM of SN 2012ab may suggest that the progenitor was an eccentric binary system undergoing eruptive mass loss.Comment: 18 pages, 12 figure

Deciphering Amyotrophic Lateral Sclerosis: What Phenotype, Neuropathology and Genetics Are Telling Us about Pathogenesis

Amyotrophic lateral sclerosis (ALS) is characterized phenotypically by progressive weakness and neuropathologically by loss of motor neurons. Phenotypically, there is marked heterogeneity. Typical ALS has mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Primary lateral sclerosis has predominant UMN involvement. Progressive muscular atrophy has predominant LMN involvement. Bulbar and limb ALS have predominant regional involvement. Frontotemporal dementia has significant cognitive and behavioral involvement. These phenotypes can be so distinctive that they would seem to have differing biology. But they cannot be distinguished, at least neuropathologically or genetically. In sporadic ALS (SALS), they all are characterized by ubiquitinated cytoplasmic inclusions of TDP-43. In familial ALS (FALS), where phenotypes are indistinguishable from SALS and similarly heterogeneous, each mutated gene has its own genetic and molecular signature. Putting this together, since the same phenotypes can have multiple causes including different gene mutations, there must be multiple molecular mechanisms causing ALS and ALS is a syndrome. But since multiple phenotypes can be caused by one single gene mutation, a single molecular mechanism can cause heterogeneity. What the mechanisms are remain unknown, but active propagation of the pathology neuroanatomically seems to be a principle component. Leading candidate mechanisms include RNA processing, cell-cell interactions between neurons and non-neuronal neighbors, focal seeding from a misfolded protein that has prion-like propagation, and fatal errors introduced during neurodevelopment of the motor system. If fundamental mechanisms can be identified and understood, ALS therapy could rationally target progression and stop disease—a goal that seems increasingly achievable.Stem Cell and Regenerative Biolog

Comparative genomic analyses reveal broad diversity in botulinum-toxin-producing Clostridia

Background: Clostridium botulinum is a diverse group of bacteria characterized by the production of botulinum neurotoxin. Botulinum neurotoxins are classified into serotypes (BoNT/A-G), which are produced by six species/Groups of Clostridia, but the genetic background of the bacteria remains poorly understood. The purpose of this study was to use comparative genomics to provide insights into the genetic diversity and evolutionary history of bacteria that produce the potent botulinum neurotoxin. Results: Comparative genomic analyses of over 170 Clostridia genomes, including our draft genome assemblies for 59 newly sequenced Clostridia strains from six continents and publicly available genomic data, provided in-depth insights into the diversity and distribution of BoNT-producing bacteria. These newly sequenced strains included Group I and II strains that express BoNT/A,/B,/E, or/F as well as bivalent strains. BoNT-producing Clostridia and closely related Clostridia species were delineated with a variety of methods including 16S rRNA gene, concatenated marker genes, core genome and concatenated multi-locus sequencing typing (MLST) gene phylogenies that related whole genome sequenced strains to publicly available strains and sequence types. These analyses illustrated the phylogenetic diversity in each Group and the diversity of genomic backgrounds that express the same toxin type or subtype. Comparisons of the botulinum neurotoxin genes did not identify novel toxin types or variants. Conclusions: This study represents one of the most comprehensive analyses of whole genome sequence data for Group I and II BoNT-producing strains. Read data and draft genome assemblies generated for 59 isolates will be a resource to the research community. Core genome phylogenies proved to be a powerful tool for differentiating BoNT-producing strains and can provide a framework for the study of these bacteria. Comparative genomic analyses of Clostridia species illustrate the diversity of botulinum-neurotoxin-producing strains and the plasticity of the genomic backgrounds in which bont genes are found.Peer reviewe