2,820 research outputs found

    There is no tame triangulation of the infinite real Grassmannian

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    We show that there is no triangulation of the infinite real Grassmannian of k-planes in R^\infty which is nicely situated with respect to the coordinate axes. In terms of matroid theory, this says there is no triangulation of the Grassmannian subdividing the matroid stratification. This is proved by an argument in projective geometry, considering a specific sequence of configurations of points in the plane.Comment: 11 page

    Improvements to 232-thorium, 230-thorium, and 231-protactinium analysis in seawater arising from GEOTRACES intercalibration

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    The GEOTRACES program requires the analysis of large numbers of seawater samples for ^(232)Th, ^(230)Th, and ^(231)Pa. During the GEOTRACES international intercalibration exercise, we encountered unexpected difficulties with recovery and contamination of these isotopes, ^(232)Th in particular. Experiments were carried out to identify the source of these issues, leading to a more streamlined and efficient procedure. The two particular problems that we identified and corrected were (1) frits in columns supplied by Bio-Rad Laboratories caused loss of Th during column chemistry and (2) new batches of AG1-X8 resin supplied by Bio-Rad Laboratories released more than 100 pg of ^(232)Th during elution of sample. To improve yields and blanks, we implemented a series of changes including switching to Eichrom anion exchange resin (100-200 ÎĽm mesh) and Environmental Express columns. All Th and Pa samples were analyzed on a Neptune multi-collector inductively-coupled-plasma mass spectrometer (MC-ICP-MS) using peak hopping of ^(230)Th and ^(229)Th on the central SEM, with either ^(232)Th, ^(236)U (or both) used to monitor for beam intensity. We used in-house laboratory standards to check for machine reproducibility, and the GEOTRACES intercalibration standard to check for accuracy. Over a 1-y period, the 2 s.d. reproducibility on the GEOTRACES SW STD 2010-1 was 2.5% for ^(230)Th, 1.8% for ^(232)Th, and 4% for ^(231)Pa. The lessons learned during this intercalibration process will be of value to those analyzing U-Th-Pa and rare earth elements as part of the GEOTRACES program as well as those using U-series elements in other applications that require high yields and low blanks, such as geochronology

    Pharmaceutical “Pay-for-Delay” Reexamined: A Dwindling Practice or a Persistent Problem?

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    The Supreme Court ruled in FTC v. Actavis that a delay in generic entry may be anticompetitive when part of a patent settlement includes a large and otherwise unjustified value transfer to the generic company, termed a reverse payment patent settlement, or “pay-for-delay.” Following Actavis, drug companies have limited the size of reverse payments and have fashioned settlement terms that include more discreet categories of compensation to generic companies. In light of the fact that such settlements retain the potential for anticompetitive effects, the apparent size of the reverse payment may no longer be a useful gauge of the legality of pay-for-delay deals. In this Article, we argue that convoluted settlements in the post-Actavis landscape that camouflage value transfers from brand-name to generic companies necessitate a shift in the focus of antitrust scrutiny to the existence of any restriction on generic entry, together with a category of patent less likely to survive a challenge. We conclude with a discussion of pay-for-delay bills in the 116th Congress and propose several reforms to deter pay-for-delay behavior

    Diamidine transport in the kinetoplastidae

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    African trypanosomes are protozoan parasites that are unable to synthesise purines de novo and as a result must scavenge them from the host environment. Purines are transported into the cell via a number of surface membrane transporters that recognise specific motifs on the substrate. These transporters can be exploited to mediate the uptake of trypanocidal drugs, such as diamidines and arsenicals. The high affinity pentamidine transporter 1 (LAPT1) and the low affinity pentamidine transporter1 (LAPTl) are involved in the uptake of the diamidine compound pentamidine and the specificities and associated affinities of these transporters for various other compounds were tested by looking at the inhibitory effect of varying concentrations of test drugs on the uptake of 3H-pentamidine. A link was found between the carbon chain length of diamidine compounds and their affinity for HAPT1 and LAPT1. For compounds containing benzene and furan rings, the position of methyl groups in relation to these structures also appears to be important. HAPT1 and LAPT1 differ in ligand recognition profdes, although both are implicated here in the uptake of Isometamidium and Ethidium Bromide, two trypanocidal drugs previously thought to be taken up by diffusion only. As there is increasing drug resistance to all trypanocidal drugs, HAPT1 and LAPT1 are extremely important as alternative delivery systems for trypanocides in the event that other transporters are lost in the field through drug pressure, for example P2. The P2 transporter known to mediate the uptake of adenosine and melaminophenylarsenicals is shown here, by using transport assays in conjunction with Michaelis-Menten kinetics, to be the sole mechanism for the uptake of veterinary drug Berenil, in Trypanosoma brucei brucei. Finally, Crithidia fasciculata, another kinetoplastid, is shown to have particular attributes, which would value this organism as a potential expression system for the characterisation of HAPT1 and LAPTI

    Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides.

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    Tissue-specific autoimmunity occurs when selected antigens presented by susceptible alleles of the major histocompatibility complex are recognized by T cells. However, the reason why certain specific self-antigens dominate the response and are indispensable for triggering autoreactivity is unclear. Spontaneous presentation of insulin is essential for initiating autoimmune type 1 diabetes in non-obese diabetic mice1,2. A major set of pathogenic CD4 T cells specifically recognizes the 12-20 segment of the insulin B-chain (B:12-20), an epitope that is generated from direct presentation of insulin peptides by antigen-presenting cells3,4. These T cells do not respond to antigen-presenting cells that have taken up insulin that, after processing, leads to presentation of a different segment representing a one-residue shift, B:13-214. CD4 T cells that recognize B:12-20 escape negative selection in the thymus and cause diabetes, whereas those that recognize B:13-21 have only a minor role in autoimmunity3-5. Although presentation of B:12-20 is evident in the islets3,6, insulin-specific germinal centres can be formed in various lymphoid tissues, suggesting that insulin presentation is widespread7,8. Here we use live imaging to document the distribution of insulin recognition by CD4 T cells throughout various lymph nodes. Furthermore, we identify catabolized insulin peptide fragments containing defined pathogenic epitopes in β-cell granules from mice and humans. Upon glucose challenge, these fragments are released into the circulation and are recognized by CD4 T cells, leading to an activation state that results in transcriptional reprogramming and enhanced diabetogenicity. Therefore, a tissue such as pancreatic islets, by releasing catabolized products, imposes a constant threat to self-tolerance. These findings reveal a self-recognition pathway underlying a primary autoantigen and provide a foundation for assessing antigenic targets that precipitate pathogenic outcomes by systemically sensitizing lymphoid tissues

    \u3csup\u3e230\u3c/sup\u3eTh and \u3csup\u3e231\u3c/sup\u3ePa on GEOTRACES GA03, the U.S. GEOTRACES North Atlantic transect, and implications for modern and paleoceanographic chemical fluxes

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    The long-lived uranium decay products 230Th and 231Pa are widely used as quantitative tracers of adsorption to sinking particles (scavenging) in the ocean by exploiting the principles of radioactive disequilibria. Because of their preservation in the Pleistocene sediment record and through largely untested assumptions about their chemical behavior in the water column, the two radionuclides have also been used as proxies for a variety of chemical fluxes in the past ocean. This includes the vertical flux of particulate matter to the seafloor, the lateral flux of insoluble elements to continental margins (boundary scavenging), and the southward flux of water out of the deep North Atlantic. In a section of unprecedented vertical and zonal resolution, the distributions of 230Th and 231Pa across the North Atlantic shed light on the marine cycling of these radionuclides and further inform their use as tracers of chemical flux. Enhanced scavenging intensities are observed in benthic layers of resuspended sediments on the eastern and western margins and in a hydrothermal plume emanating from the Mid-Atlantic Ridge. Boundary scavenging is clearly expressed in the water column along a transect between Mauritania and Cape Verde which is used to quantify a bias in sediment fluxes calculated using 230Th-normalization and to demonstrate enhanced 231Pa removal from the deep North Atlantic by this mechanism. The influence of deep ocean ventilation that leads to the southward export of 231Pa is apparent. The 231Pa/230Th ratio, however, predominantly reflects spatial variability in scavenging intensity, complicating its applicability as a proxy for the Atlantic meridional overturning circulation
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