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We present an analysis that synthesizes information on the sequence, structure, and motifs of antigenic peptides, which previously appeared to be in conflict. Fourier analysis of T-cell antigenic peptides indicates a periodic variation in amino acid polarities of 3-3.6 residues per period, suggesting an amphipathic alpha-helical structure. However, the diffraction patterns of major histocompatibility complex (MHC) molecules indicate that their ligands are in an extended non-alpha-helical conformation. We present two mutually consistent structural explanations for the source of the alpha-helical periodicity, based on an observation that the side chains of MHC-bound peptides generally partition with hydrophobic (hydrophilic) side chains pointing into (out of) the cleft. First, an analysis of haplotype-dependent peptide motifs indicates that the locations of their defining residues tend to force a period 3-4 variation in hydrophobicity along the peptide sequence, in a manner consistent with the spacing of pockets in the MHC. Second, recent crystallographic determination of the structure of a peptide bound to a class II MHC molecule reveals an extended but regularly twisted peptide with a rotation angle of about 130 degrees. We show that similar structures with rotation angles of 100-130 degrees are energetically acceptable and also span the length of the MHC cleft. These results provide a sound physical chemical and structural basis for the existence of a haplotype-independent antigenic motif which can be particularly important in limiting the search time for antigenic peptides.

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This work was supported by the Brazilian agencies FAPESP and CNPq. MSB also acknowledges the Engineering and Physical Sciences Research Council grant Ref. EP/I032606/1. GID thanks Felipe A. C. Pereira for fruitful discussions.

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The aim of the present paper is to study the periodic orbits of a perturbed self excited rigid body with a fixed point. For studying these periodic orbits we shall use averaging theory of first order.

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Handwritten order to Penn Townsend to pay scholarship funds to student Hull Abbot (Harvard AB 1720), signed by Benjamin Wadsworth, John Marion, and Thomas Hubbart.

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Handwritten order to Penn Townsend to pay scholarship funds to student Josiah Cotton (Harvard AB 1722), signed by Benjamin Wadsworth, Thomas Foxcroft, Samuel Marshall, and Jonathan Williams.

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Handwritten order to Penn Townsend to pay scholarship funds to Benjamin Webb on behalf of his son Nathan Webb (Harvard AB 1725), signed by Thomas Foxcroft, John Marion, Samuel Marshall, and Jonathan Williams.

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Handwritten order to Penn Townsend to pay scholarship funds to Rowland Cotton on behalf of his son Ward Cotton (Harvard AB 1729), signed by Thomas Foxcroft, John Marion, Samuel Marshall, and Jonathan Williams.

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Handwritten order to John Sale to pay scholarship funds to Nathanael Gardner on behalf of his son Nathaniel Gardner (Harvard AB 1739), signed by Thomas Foxcroft, Charles Chauncey, Samuel Marshall, Zechariah Thayer, and Thomas Waite.

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Handwritten order to John Sale to pay scholarship funds to Nathanael Gardner on behalf of his son Nathaniel Gardner (Harvard AB 1739), signed by Thomas Foxcroft, Charles Chauncey, Samuel Marshall, Thomas Waite, and Cornelius Thayer.

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Handwritten order to John Sale to pay scholarship funds to Nathanael Gardner on behalf of his son Nathaniel Gardner (Harvard AB 1739), signed by Thomas Foxcroft, Charles Chauncey, Samuel Marshall, Thomas Waite, and Cornelius Thayer, and Jonathan Williams.

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Handwritten order to John Sale to pay scholarship funds to Deacon Jonathan Williams, signed by Thomas Foxcroft, Charles Chauncey, Thomas Waite, and Daniel Marsh.

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Handwritten order to John Sale to pay scholarship funds to Robert Williams on behalf of his nephew William Bradford (Harvard AB 1760), signed by Thomas Foxcroft, Charles Chauncey, Thomas Waite, Jonathan Williams, and Daniel Marsh.

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Handwritten order to John Sale to pay scholarship funds Robert Williams, signed by Thomas Foxcroft, Charles Chauncey, Thomas Waite, Jonathan Williams, and Daniel Marsh.

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Handwritten order to John Sale to pay scholarship funds to Deacon Daniel Marsh, signed by Thomas Foxcroft and Charles Chauncey