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

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

Energy levels and lifetimes of Gd IV and enhancement of the electron dipole moment

We have calculated energy levels and lifetimes of 4f7 and 4f6 5d configurations of Gd IV using Hartree-Fock and configuration interaction methods. This allows us to reduce significantly the uncertainty of the theoretical determination of the electron electric dipole moment (EDM) enhancement factor in this ion and, correspondingly, in gadolinium-containing garnets for which such measurements were recently proposed. Our new value for the EDM enhancement factor of Gd+3 is -2.2 +- 0.5. Calculations of energy levels and lifetimes for Eu~III are used to control the accuracy.Comment: Submitted to Phys. Rev. A 6 pages, 0 figures, 3 table

Free-flight investigation of the stability and control characteristics of a STOL model with an externally blown jet flap

The stability and control characteristics of a four-engine turbofan STOL transport model having an externally blown jet flap have been investigated by means of the flying-model technique in the Langley full-scale tunnel. The flight characteristics of the model were investigated under conditions of symmetric and asymmetric (one engine inoperative) thrust at lift coefficients up to 9.5 and 5.5, respectively. Static characteristics were studied by conventional power-on force tests over the flight-test angle-of-attack range including the stall. In addition to these tests, dynamic longitudinal and lateral stability calculations were performed for comparison with the flight-test results and for use in correlating the model results with STOL handling-qualities criteria

Bethe lattice solution of a model of SAW's with up to 3 monomers per site and no restriction

In the multiple monomers per site (MMS) model, polymeric chains are represented by walks on a lattice which may visit each site up to K times. We have solved the unrestricted version of this model, where immediate reversals of the walks are allowed (RA) for K = 3 on a Bethe lattice with arbitrary coordination number in the grand-canonical formalism. We found transitions between a non-polymerized and two polymerized phases, which may be continuous or discontinuous. In the canonical situation, the transitions between the extended and the collapsed polymeric phases are always continuous. The transition line is partly composed by tricritical points and partially by critical endpoints, both lines meeting at a multicritical point. In the subspace of the parameter space where the model is related to SASAW's (self-attracting self-avoiding walks), the collapse transition is tricritical. We discuss the relation of our results with simulations and previous Bethe and Husimi lattice calculations for the MMS model found in the literature.Comment: 25 pages, 9 figure

Ada style guide (version 1.1)

Ada is a programming language of considerable expressive power. The Ada Language Reference Manual provides a thorough definition of the language. However, it does not offer sufficient guidance on the appropriate use of Ada's powerful features. For this reason, the Goddard Space Flight Center Ada User's Group has produced this style guide which addresses such program style issues. The guide covers three areas of Ada program style: the structural decomposition of a program; the coding and the use of specific Ada features; and the textural formatting of a program

The Modal Logics of Kripke-Feferman Truth

We determine the modal logic of fixed-point models of truth and their axiomatizations by Solomon Feferman via Solovay-style completeness results

Fixed base simulator study of an externally blown flap STOL transport airplane during approach and landing

A fixed-base simulator study was conducted to determine the flight characteristics of a representative STOL transport having a high wing and equipped with an external-flow jet flap in combination with four high-bypass-ratio fan-jet engines during the approach and landing. Real-time digital simulation techniques were used. The computer was programed with equations of motion for six degrees of freedom and the aerodynamic inputs were based on measured wind-tunnel data. A visual display of a STOL airport was provided for simulation of the flare and touchdown characteristics. The primary piloting task was an instrument approach to a breakout at a 200-ft ceiling with a visual landing