Scattering of fundamental states of type IIB supergravity and superstring theory is discussed at low orders in perturbation theory in the background of a D-instanton. The integration over fermionic zero modes in both the low energy supergravity and in the string theory leads to explicit nonperturbative terms in the effective action. These include a single instanton correction to the known tree-level and one-loop $R^4$ interactions. The `spectrum' of multiply-charged D-instantons is deduced by T-duality in nine dimensions from multiply-wound world-lines of marginally-bound D-particles. This, and other clues, lead to a conjectured SL(2,Z) completion of the $R^4$ terms which suggests that they are not renormalized by perturbative corrections in the zero-instanton sector beyond one loop. The string theory unit-charged D-instanton gives rise to point-like effects in fixed-angle scattering, raising unresolved issues concerning distance scales in superstring theory.Comment: 31 pages, 6 figures, Latex, Reference added, corrected coefficients in expansion of generalized Eisenstein series in equation 66 now agree with hep-th/970414

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Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent. The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia

Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.