The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets.

Glycosylation-inhibiting factor (GIF) is a cytokine that is involved in the regulation of IgE synthesis. The crystal structure of recombinant human GIF was determined by the multiple isomorphous replacement method. The structure was refined to an R factor of 0.168 at 1.9 angstrom resolution. The overall structure is seen to consist of three interconnected subunits forming a barrel with three 6-stranded beta-sheets on the inside and six alpha-helices on the outside. There is a 5-angstrom-diameter "hole" through the middle of the barrel. The barrel structure of GIF in part resembles other "trefoil" cytokines such as interleukin 1 and fibroblast growth factor. Each subunit has a new class of alpha + beta sandwich structure consisting of two beta-alpha-beta motifs. These beta-alpha-beta motifs are related by a pseudo-twofold axis and resemble both interleukin 8 and the peptide binding domain of major histocompatibility complex protein, although the topology of the polypeptide chain is quite different.

Crystal structure of the membrane-exposed domain from a respiratory quinol oxidase complex with an engineered dinuclear copper center.

Cytochrome oxidase is a membrane protein complex that catalyzes reduction of molecular oxygen to water and utilizes the free energy of this reaction to generate a transmembrane proton gradient during respiration. The electron entry site in subunit II is a mixed-valence dinuclear copper center in enzymes that oxidize cytochrome c. This center has been lost during the evolution of the quinoloxidizing branch of cytochrome oxidases but can be restored by engineering. Herein we describe the crystal structures of the periplasmic fragment from the wild-type subunit II (CyoA) of Escherichia coli quinol oxidase at 2.5-A resolution and of the mutant with the engineered dinuclear copper center (purple CyoA) at 2.3-A resolution. CyoA is folded as an 11-stranded mostly antiparallel beta-sandwich followed by three alpha-helices. The dinuclear copper center is located at the loops between strands beta 5-beta 6 and beta 9-beta 10. The two coppers are at a 2.5-A distance and symmetrically coordinated to the main ligands that are two bridging cysteines and two terminal histidines. The residues that are distinct in cytochrome c and quinol oxidases are around the dinuclear copper center. Structural comparison suggests a common ancestry for subunit II of cytochrome oxidase and blue copper-binding proteins.

Mutagenesis in the C-terminal region of human interleukin 5 reveals a central patch for receptor alpha chain recognition.

Cassette mutagenesis was used to identify side chains in human interleukin 5 (hIL-5) that mediate binding to hIL-5 receptor alpha chain (hIL-5R alpha). A series of single alanine substitutions was introduced into a stretch of residues in the C-terminal region, including helix D, which previously had been implicated in receptor alpha chain recognition and which is aligned on the IL-5 surface so as to allow the topography of receptor binding residues to be examined. hIL-5 and single site mutants were expressed in COS cells, their interactions with hIL-5R alpha were measured by a sandwich surface plasmon resonance biosensor method, and their biological activities were measured by an IL-5-dependent cell proliferation assay. A pattern of mutagenesis effects was observed, with greatest impact near the interface between the two four-helix bundles of IL-5, in particular at residues Glu-110 and Trp-111, and least at the distal ends of the D helices. This pattern suggests the possibility that residues near the interface of the two four-helix bundles in hIL-5 comprise a central patch or hot spot, which constitutes an energetically important alpha chain recognition site. This hypothesis suggests a structural explanation for the 1:1 stoichiometry observed for the complex of hIL-5 with hIL-5R alpha.

Considerations on the folding topology and evolutionary origin of cadherin domains.

Cell-cell adhesion in zonula adherens and desmosomal junctions is mediated by cadherins, and recent crystal structures of the first domain from murine N-cadherin provide a plausible molecular basis for this adhesive action. A structure-based sequence analysis of this adhesive domain indicates that its fold is common to all extracellular cadherin domains. The cadherin folding topology is also shown to be similar to immunoglobulin-like domains and to other Greek-key beta-sandwich structures, as diverse as domains from plant cytochromes, bacterial cellulases, and eukaryotic transcription factors. Sequence similarities between cadherins and these other molecules are very low, however, and intron patterns are also different. On balance, independent origins for a favorable folding topology seem more likely than evolutionary divergence from an ancestor common to cadherins and immunoglobulins.

Student notebook of Thomas Prince, ca. 1707

Paper notebook in Latin on classical Greek grammar. The name "Thomas Prince" appears on the first page. The manuscript is undated. Based on the signature, this volume is assumed to have belonged to Thomas Prince, Sr., although it is undated and may have indeed belonged to Thomas Prince, Jr.

Commonplace book of Nathaniel Freeman, 1786-1787

Nathaniel Freeman made entries in this commonplace book between 1786 and 1787, while he was an undergraduate at Harvard College. The book includes the notes Freeman took during three of Hollis Professor Samuel Williams' "Course of Experimental Lectures," and cover Williams' lectures on "The Nature & Properties of Matter," "Attraction & Repulsion," and "The Nature, Kind, & Affections [?] of Motion." These notes also include one diagram. The book also includes forensic compositions on the subjects of capital punishment, the probability of "the immortality of the soul," and "whether there be any disinterested benevolence." It also includes a poem Freeman composed for his uncle, Edmund Freeman; an anecdote about Philojocus and Gripus; an essay called "Character"; a draft of a letter to the Harvard Corporation requesting that, in light of the public debt, the Commencement ceremonies be held privately to lower expenses and exhibit the merits of economy; and an "epistle" to his father, requesting money. This epistle begins: "Most honored sire, / Thy son, poor Nat, in humble strains, / Impell'd by want, thy generous bounty claims."

Potential sites for wireless telecommunications facilities

created by the Cape Cod Commission's geographic information systems department.

New Hampshire, 1816 (Image 5 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 5 of 6 total images, representing the center west portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

Barnstable, Dukes, and Nantucket counties, Massachusetts, 1858 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of the counties of Barnstable, Dukes and Nantucket, Massachusetts, the details from actual surveys under the direction of Henry F. Walling, supt. of the state map. It was published by D.R. Smith & Co., in 1858. Scale 1:63,360. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, public buildings, schools, churches, cemeteries, industry locations (e.g. mills, factories, mines, etc.), private buildings with names of property owners, town and county boundaries and more. Relief is shown by hachures. It includes many cadastral insets of individual county towns and villages, and an inset geological map of county. Includes also ill., business directories, and tables of statistics and distances. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Barnstable, Massachusetts 15 Minute Digital Raster Graphic

This layer is a digital raster graphic of the historic 15-minute USGS topographic quadrangle map of Barnstable, Massachusetts. The edition date is 1893 and the map was reprinted in 1907. A digital raster graphic (DRG) is a scanned image of a U.S. Geological Survey (USGS) standard series topographic map, including all map collar information. The image inside the map neatline is geo-referenced to the surface of the earth and fit to the Universal Transverse Mercator projection. The horizontal positional accuracy and datum of the DRG matches the accuracy and datum of the source map. The names of quadrangles which border this one appear on the map collar in their respective positions (N,S,E,W) in relation to this map.

Falmouth, Massachusetts 15 Minute Digital Raster Graphic

This layer is a digital raster graphic of the historic 15-minute USGS topographic map of the Falmouth, Massachusetts quadrangle. The survey date (ground condition) of this map is 1886 and the edition date is August, 1893. A digital raster graphic (DRG) is a scanned image of a U.S. Geological Survey (USGS) standard series topographic map, including all map collar information. The image inside the map neatline is geo-referenced to the surface of the earth and fit to the Universal Transverse Mercator projection. The horizontal positional accuracy and datum of the DRG matches the accuracy and datum of the source map. The names of quadrangles which border this one appear on the map collar in their respective positions (N,S,E,W) in relation to this map.

Plymouth, Massachusetts 15 Minute Digital Raster Graphic

This layer is a digital raster graphic of the historic 15-minute USGS topographic map of the Plymouth, Massachusetts quadrangle. The survey date (ground condition) of the original paper map is 1885-1886, the edition date is August, 1894 and this map has a reprint date of March 1898. A digital raster graphic (DRG) is a scanned image of a U.S. Geological Survey (USGS) standard series topographic map, including all map collar information. The image inside the map neatline is geo-referenced to the surface of the earth and fit to the Universal Transverse Mercator projection. The horizontal positional accuracy and datum of the DRG matches the accuracy and datum of the source map.

Avaliação in vitro da microinfiltração marginal em restaurações a resina composta, utilizando diferentes substitutos dentinários

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Radiolarian-based paleotemperatures of ODP Site 177-1089 in the Atlantic Sector of the Southern Ocean

Two cores, Site 1089 (ODP Leg 177) and PS2821-1, recovered from the same location (40°56'S; 9°54'E) at the Subtropical Front (STF) in the Atlantic Sector of the Southern Ocean, provide a high-resolution climatic record, with an average temporal resolution of less than 600 yr. A multi-proxy approach was used to produce an age model for Core PS2821-1, and to correlate the two cores. Both cores document the last climatic cycle, from Marine Isotopic Stage 6 (MIS 6, ca. 160 kyr BP, ka) to present. Summer sea-surface temperatures (SSSTs) have been estimated, with a standard error of ca. +/-1.16°C, for the down core record by using Q-mode factor analysis (Imbrie and Kipp method). The paleotemperatures show a 7°C warming at Termination II (last interglacial, transition from MIS 6 to MIS 5). This transition from glacial to interglacial paleotemperatures (with maximum temperatures ca. 3°C warmer than present at the core location) occurs earlier than the corresponding shift in delta18O values for benthic foraminifera from the same core; this suggests a lead of Southern Ocean paleotemperature changes compared to the global ice-volume changes, as indicated by the benthic isotopic record. The climatic evolution of the record continues with a progressive temperature deterioration towards MIS 2. High-frequency, millennial-scale climatic instability has been documented for MIS 3 and part of MIS 4, with sudden temperature variations of almost the same magnitude as those observed at the transitions between glacial and interglacial times. These changes occur during the same time interval as the Dansgaard-Oeschger cycles recognized in the delta18Oice record of the GRIP and GISP ice cores from Greenland, and seem to be connected to rapid changes in the STF position in relation to the core location. Sudden cooling episodes ('Younger Dryas (YD)-type' and 'Antarctic Cold Reversal (ACR)-type' of events) have been recognized for both Termination I (ACR-I and YD-I events) and II (ACR-II and YD-II events), and imply that our core is located in an optimal position in order to record events triggered by phenomena occurring in both hemispheres. Spectral analysis of our SSST record displays strong analogies, particularly for high, sub-orbital frequencies, to equivalent records from Vostok (Antarctica) and from the Subtropical North Atlantic ocean. This implies that the climatic variability of widely separated areas (the Antarctic continent, the Subtropical North Atlantic, and the Subantarctic South Atlantic) can be strongly coupled and co-varying at millennial time scales (a few to 10-ka periods), and eventually induced by the same triggering mechanisms. Climatic variability has also been documented for supposedly warm and stable interglacial intervals (MIS 1 and 5), with several cold events which can be correlated to other Southern Ocean and North Atlantic sediment records.