Introduction : Piracy and occasional state power

States exert their power over maritime predation only occasionally depending on prevalent circumstances. Historically, when states have perceived and attempted to address a problem of piracy, they have encountered severe limits on their abilities to manage private maritime enterprise in waters under their purported control. Despite the popular conception that piracy falls into the legal category of 'universal jurisdiction', such jurisdiction has only been employed sporadically. In reality, despite high-profile 'terror' campaigns against pirates, states regularly employed alternative means of suppression, including negotiation, legal posturing and co-optation. The four articles in this Forum provide detailed case studies of the occasional use of state power to regulate maritime predation in diverse waters and contexts. In these examples, states respectively negotiated with maritime communities in medieval England, sought a monopoly on violence in the South China Sea, collaborated with other states to police colonial Hong Kong, and dealt diplomatically with a local pirate hero to defend New Orleans. Across each article, the 'state' faced a particular problem of piracy, but could only occasionally exert power to manage it

Multibeam Sonar Backscatter Lineaments and Anthropogenic Organic Components in Lacustrine Silty Clay, Evidence of Shipping in Western Lake Ontario

A multibeam sonar survey (95 kHz) covering more than 500 km2 of western Lake Ontario revealed anomalous lineaments of relatively high backscatter. The lineaments did not align with or parallel the most prominent structural zones beneath the lake as expected. Instead, the principal lineaments lay on lines between ports on opposite sides of the lake, especially between Toronto and Welland Canal, and Toronto and Niagara River mouth. As the lineaments underlie current and historical shipping routes used during the steamship era, they are interpreted as an acoustic response to shipping debris cumulated in the near-surface bottom sediment. An exploratory study of the organic components in the silty clay surface sediment, using geochemical and petrological techniques, shows that the upper 10 cm commonly contains silt-sized particles of anthropogenic origin, especially combustion residues. Combustion residues are more abundant on or near the lineaments, consistent with an origin related to shipping. Enhanced acoustic backscatter is evident where silt-sized combustion particles are hosted in dominantly clay-sized sediment. The coarser- grained anthropogenic particles increase the acoustic impedance of the lakebed relative to the bottom water as well as the roughness and volume scattering contributions to lakebed backscatter

Cultivation of Heligmosomoides polygyrus:An immunomodulatory nematode parasite and its secreted products

Heligmosomoides polygyrus (formerly known as Nematospiroides dubius, and also referred to by some as H. bakeri) is a gastrointestinal helminth that employs multiple immunomodulatory mechanisms to establish chronic infection in mice and closely resembles prevalent human helminth infections. H. polygyrus has been studied extensively in the field of helminth-derived immune regulation and has been found to potently suppress experimental models of allergy and autoimmunity (both with active infection and isolated secreted products). The protocol described in this paper outlines management of the H. polygyrus life cycle for consistent production of L3 larvae, recovery of adult parasites, and collection of their excretory-secretory products (HES)

Differences in Reversion of Resistance Mutations to Wild-Type under Structured Treatment Interruption and Related Increase in Replication Capacity

The CPCRA 064 study examined the effect of structured treatment interruption (STI) of up to 4 months followed by salvage treatment in patients failing therapy with multi-drug resistant HIV. We examined the relationship between the reversion rate of major reverse transcriptase (RT) resistance-associated mutations and change in viral replication capacity (RC). The dataset included 90 patients with RC and genotypic data from virus samples collected at 0 (baseline), 2 and 4 months of STI.Rapid shift towards wild-type RC was observed during the first 2 months of STI. Median RC increased from 47.5% at baseline to 86.0% at 2 months and to 97.5% at 4 months. Between baseline and 2 months of STI, T215F had the fastest rate of reversion (41%) and the reversion of E44D and T69D was associated with the largest changes in RC. Among the most prevalent RT mutations, M184V had the fastest rate of reversion from baseline to 2 months (40%), and its reversion was associated with the largest increase in RC. Most rates of reversion increased between 2 months and 4 months, but the change in RC was more limited as it was already close to 100%. The highest frequency of concurrent reversion was found for L100I and K103N. Mutagenesis tree models showed that M184V, when present, was overall the first mutation to revert among all the RT mutations reported in the study.Longitudinal analysis of combined phenotypic and genotypic data during STI showed a large amount of variability in prevalence and reversion rates to wild-type codons among the RT resistance-associated mutations. The rate of reversion of these mutations may depend on the extent of RC increase as well as the co-occurring reversion of other mutations belonging to the same mutational pathway

Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching

Nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch recombination (CSR) in peripheral B lymphocytes. We now show that CD21-cre–mediated deletion of the Xrcc4 NHEJ gene in p53-deficient peripheral B cells leads to recurrent surface Ig-negative B lymphomas (“CXP lymphomas”). Remarkably, CXP lymphomas arise from peripheral B cells that had attempted both receptor editing (secondary V[D]J recombination of Igκ and Igλ light chain genes) and IgH CSR subsequent to Xrcc4 deletion. Correspondingly, CXP tumors frequently harbored a CSR-based reciprocal chromosomal translocation that fused IgH to c-myc, as well as large chromosomal deletions or translocations involving Igκ or Igλ, with the latter fusing Igλ to oncogenes or to IgH. Our findings reveal peripheral B cells that have undergone both editing and CSR and show them to be common progenitors of CXP tumors. Our studies also reveal developmental stage-specific mechanisms of c-myc activation via IgH locus translocations. Thus, Xrcc4/p53-deficient pro–B lymphomas routinely activate c-myc by gene amplification, whereas Xrcc4/p53-deficient peripheral B cell lymphomas routinely ectopically activate a single c-myc copy

Dry Climate Disconnected the Laurentian Great Lakes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94725/1/eost16649.pd

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios+ T cells and autoantibodies

Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1Anaef, with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1Anaef mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44hi Helios+ PD-1+ CD4+ T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1Anaef is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1Anaef naïve CD4+ T cells. CD44 expression, CD4+ T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1AnaefMtorchino double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1Anaef T cell dysregulation

Rasgrp1 mutation increases naïve T-cell CD44 expression and drives mTOR-dependent accumulation of Helios⁺ T cells and autoantibodies

Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1ᴬⁿᵃᵉᶠ, with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide exchange factor. Rasgrp1ᴬⁿᵃᵉᶠ mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44hi Helios⁺ PD-1⁺ CD4⁺ T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1ᴬⁿᵃᵉᶠ is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1ᴬⁿᵃᵉᶠ naïve CD4⁺ T cells. CD44 expression, CD4⁺ T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1ᴬⁿᵃᵉᶠMtorᶜʰⁱⁿᵒ double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1ᴬⁿᵃᵉᶠ T cell dysregulation

Supernova Observation Via Neutrino-Nucleus Elastic Scattering in the CLEAN Detector

Development of large mass detectors for low-energy neutrinos and dark matter may allow supernova detection via neutrino-nucleus elastic scattering. An elastic-scattering detector could observe a few, or more, events per ton for a galactic supernova at 10 kpc ($3.1 \times 10^{20}$ m). This large yield, a factor of at least 20 greater than that for existing light-water detectors, arises because of the very large coherent cross section and the sensitivity to all flavors of neutrinos and antineutrinos. An elastic scattering detector can provide important information on the flux and spectrum of $\nu_\mu$ and $\nu_\tau$ from supernovae. We consider many detectors and a range of target materials from $^4$He to $^{208}$Pb. Monte Carlo simulations of low-energy backgrounds are presented for the liquid-neon-based Cryogenic Low Energy Astrophysics with Noble gases (CLEAN) detector. The simulated background is much smaller than the expected signal from a galactic supernova.Comment: 10 pages, 5 figures, submitted to Phys. Rev.