China Sea /

Relief shown by hachures. Depths shown by soundings.

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell-Driven Protective Response

Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199-314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73 +/- 12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-gamma secretion, ratios of IFN-gamma/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNF alpha/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5-88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-gamma/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens.

[C II] and 12^CO(1-0) emission maps in HLSJ091828.6+514223: a strongly lensed interacting system AT z = 5.24

We present Submillimeter Array [C II] 158 μm and Karl G. Jansky Very Large Array 12^CO(1-0) line emission maps for the bright, lensed, submillimeter source at z = 5.2430 behind A 773: HLSJ091828.6+514223 (HLS0918). We combine these measurements with previously reported line profiles, including multiple 12^CO rotational transitions, [C I], water, and [N II], providing some of the best constraints on the properties of the interstellar medium in a galaxy at z > 5. HLS0918 has a total far-infrared (FIR) luminosity L_FIR(8–1000 μm) = (1.6 ± 0.1) × 10^14 L_☉ μ^–1, where the total magnification μ_total = 8.9 ± 1.9, via a new lens model from the [C II] and continuum maps. Despite a HyLIRG luminosity, the FIR continuum shape resembles that of a local LIRG. We simultaneously fit all of the observed spectral line profiles, finding four components that correspond cleanly to discrete spatial structures identified in the maps. The two most redshifted spectral components occupy the nucleus of a massive galaxy, with a source-plane separation <1 kpc. The reddest dominates the continuum map (demagnified L_FIR, component = (1.1 ± 0.2) × 10^13 L_☉) and excites strong water emission in both nuclear components via a powerful FIR radiation field from the intense star formation. A third star-forming component is most likely a region of a merging companion (ΔV ~ 500 km s^–1) exhibiting generally similar gas properties. The bluest component originates from a spatially distinct region and photodissociation region analysis suggests that it is lower density, cooler, and forming stars less vigorously than the other components. Strikingly, it has very strong [N II] emission, which may suggest an ionized, molecular outflow. This comprehensive view of gas properties and morphology in HLS0918 previews the science possible for a large sample of high-redshift galaxies once ALMA attains full sensitivity.

Some Acct. of Sev'l things relating to the College contain'd in ye Charter Laws &c with references to the originals (manuscript partial copy), [1721 October]

Two octavo-sized leaves with four half-page columns containing a handwritten copy, made by President Leverett, of an October 17, 1721 a paper composed by Nicholas Sever and William Welsteed to Judge Samuel Sewall.

An Acct of Several things relating to ye Coll: contained in ye Charter Laws &c: w'th references to the Originals (manuscript copy), 1721 October 17

Two folio-sized leaves containing a three-page handwritten report sent by Nicholas Sever and William Welsteed to Judge Samuel Sewall outlining the historical precedence for the Tutors' claims. The body of the text begins, "What we assert in ye first place..."

[ Fetâvâ] : manuscript, 1132 [ca. 1720 C.E.]

A typical fatwa collection covering almost all aspects of law: prayers, ablution, alms, fasting, divorce, capital punishment, etc.

The roads of Italy : engraved on twenty six copper-plates from the manuscript drawings of a nobleman of distinction, wherein are found all the cities, towns, villages, rivers, remarkable views, [et]c...

Portadas paralelas en francés e italiano con el siguiente título : Le portefeuille nécessaire à tous les seigneurs qui font le tour d'Italie : où l'on trouve une description exacte des villes, bourgs, villages [et] rivières ... en vingt-six cartes topographiques ... = Il portafoglio necessario a tutti quelli che fanno il giro d'Italia ...

Maps, &c. of the mineral region of Lake Superior.

Cover title.

Original journals of the Lewis and Clark Expedition, 1804-1806; printed from the original manuscripts in the library of the American Philosophical Society and by direction of its committee on historical documents, together with manuscript material of Lewis and Clark from other sources, including note-books, letters, maps, etc., and the journals of Charles Floyd and Joseph Whitehouse, now for the first time published in full and exactly as written.

Vol. 8 has title: Atlas accompanying the original journals of the Lewis and Clark Expedition, 1804-1806, being facsimile reproductions of maps, chiefly by William Clark ... Now for the first time published, from the original manuscripts ... together with a modern map of the route ...

Memoirs, maps, &c., issued by the Geological Survey of the United Kingdom and the Museum of Practical Geology.

At head of title: List F.

The wonders of the heavens, being a popular view of astronomy, including a full illustration of the mechanism of the heavens; embracing the sun, moon, and stars, with descriptions of the planets, comets, fixed stars, double stars, the constellations, the galaxy, or milky-way, the zodiacal light, aurora borealis, or northern lights, meteors, clouds, falling stars, aërolites, & c. Illustrated by numerous maps and engravings.

In double columns.

Honduras interoceanic railway: with maps of the line and ports; and an appendix, containing report of Admiral R. Fitzroy, R.N., the charter, illustrative documents, treaties, &c.

Mode of access: Internet.

The traveller's guide through the state of New York, Canada, &c : embracing a general discription of the city of New-York; the Hudson river guide, and the fashionable tour to the Springs and Niagara falls; with steam-boat, rail-road, and stage routes; accompanied by correct maps.

"Canals and railroads in the state of New York": p.69

Letters of Lady Rachel Russell : from the manuscript in the library at Woburn Abbey : with an introduction vindicating the character of Lord Russell against Sir John Dalrymple, &c., and the trial of Lord William Russell for high treason.

Mode of access: Internet.