Influence of Linker Length and Composition on Enzymatic Activity and Ribosomal Binding of Neomycin Dimers

The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by AMEs also showed increased bacterial A site binding, with one compound (compound 14) even showing substantially reduced human A site binding. The urea-linked dimers showed a substantial decrease in activity by AMEs when a conformationally restrictive phenyl linker was introduced. The information learned herein advances our understanding of the importance of the linker length and composition for the generation of dimeric aminoglycoside antibiotics capable of avoiding the action of AMEs and selective binding to the bacterial rRNA over binding to the human rRNA

On the Instanton Contributions to the Masses and Couplings of E6E_6 Singlets

We consider the gauge neutral matter in the low--energy effective action for string theory compactification on a \cym\ with $(2,2)$ world--sheet supersymmetry. At the classical level these states (the \sing's of $E_6$) correspond to the cohomology group H^1(\M,{\rm End}\>T). We examine the first order contribution of instantons to the mass matrix of these particles. In principle, these corrections depend on the \K\ parameters $t_i$ through factors of the form e^{2\p i t_i} and also depend on the complex structure parameters. For simplicity we consider in greatest detail the quintic threefold \cp4[5]. It follows on general grounds that the total mass is often, and perhaps always, zero. The contribution of individual instantons is however nonzero and the contribution of a given instanton may develop poles associated with instantons coalescing for certain values of the complex structure. This can happen when the underlying \cym\ is smooth. Hence these poles must cancel between the coalescing instantons in order that the superpotential be finite. We examine also the \Y\ couplings involving neutral matter \ysing\ and neutral and charged fields \ymix, which have been little investigated even though they are of phenomenological interest. We study the general conditions under which these couplings vanish classically. We also calculate the first--order world--sheet instanton correction to these couplings and argue that these also vanish.Comment: 40 pages, plain TeX with epsf, one uuencoded figur

On Semi-Periods

The periods of the three-form on a Calabi-Yau manifold are found as solutions of the Picard-Fuchs equations; however, the toric varietal method leads to a generalized hypergeometric system of equations which has more solutions than just the periods. This same extended set of equations can be derived from symmetry considerations. Semi-periods are solutions of this extended system. They are obtained by integration of the three-form over chains; these chains can be used to construct cycles which, when integrated over, give periods. In simple examples we are able to obtain the complete set of solutions for the extended system. We also conjecture that a certain modification of the method will generate the full space of solutions in general.Comment: 18 pages, plain TeX. Revised derivation of $\Delta^*$ system of equations; version to appear in Nuclear Physics

On Periods for String Compactifications

Motivated by recent developments in the computation of periods for string compactifications with $c=9$, we develop a complementary method which also produces a convenient basis for related calculations. The models are realized as Calabi--Yau hypersurfaces in weighted projective spaces of dimension four or as Landau-Ginzburg vacua. The calculation reproduces known results and also allows a treatment of Landau--Ginzburg orbifolds with more than five fields.Comment: HUPAPP-93/6, IASSNS-HEP-93/80, UTTG-27-93. 21 pages,harvma

Mass Reduction Patterning of Silicon-on-oxide-based Micromirrors

It has long been recognized in the design of micromirror-based optical systems that balancing static flatness of the mirror surface through structural design with the system’s mechanical dynamic response is challenging. Although a variety of mass reduction approaches have been presented in the literature to address this performance trade, there has been little quantifiable comparison reported. In this work, different mass reduction approaches, some unique to the work, are quantifiably compared with solid plate thinning in both curvature and mass using commercial finite element simulation of a specific square silicon-on-insulator–based micromirror geometry. Other important considerations for micromirror surfaces, including surface profile and smoothness, are also discussed. Fabrication of one of these geometries, a two-dimensional tessellated square pattern, was performed in the presence of a 400-μm-tall central post structure using a simple single mask process. Limited experimental curvature measurements of fabricated samples are shown to correspond well with properly characterized simulation results and indicate ∼67% improvement in radius of curvature in comparison to a solid plate design of equivalent mass

Production of Pairs of Sleptoquarks in Hadron Colliders

We calculate the cross section for the production of pairs of scalar leptoquarks (sleptoquarks) in a supersymmetric $E_6$ model, at hadron colliders. We estimate higher order corrections by including $\pi^2$ terms induced by soft-gluon corrections. Discovery bounds on the sleptoquark mass are estimated at collider energies of 1.8, 2, and 4 TeV (Tevatron), and 16 TeV (LHC).Comment: 8 pages, REVTEX, (1 fig. available on request), LAVAL-PHY-94-13/McGILL-94-26/SPhT-94-07

Leptoquark pair production at the Fermilab Tevatron: Signal and backgrounds

We perform a Monte-Carlo simulation of scalar leptoquark pair production at the Tevatron (energy =1.8 TeV and luminosity =100 pb^{-1}) with ISAJET. We also investigate the dominant sources of Standard Model background: Z*jj, ZZ production and heavy quark top-antitop. We find that the top-antitop background is the most important except near the Z pole where the Z*jj background is peaked. We also evaluate the signal-to-background ratio and find a discovery reach of 130 GeV (170 GeV) for a branching ratio of B(LQ-> eq)=0.5 (B=1).Comment: 8 pages, 6 figures, latex (revtex

Sex with Older Partners Is Associated With Primary HIV Infection Among Men Who Have Sex With Men in North Carolina

Studies from the 1990s suggested sex with older partners was associated with HIV infection. We evaluated the hypothesized association between primary HIV infection (PHI) and having older sexual partners among men who have sex with men (MSM)

Yang-Mills- and D-instantons

In these lectures, which are written at an elementary and pedagogical level, we discuss general aspects of (single) instantons in SU(N_c) Yang-Mills theory, and then specialize to the case of N = 4 supersymmetry and the large N_c limit. We show how to determine the measure of collective coordinates and compute instanton corrections to certain correlation functions. We then relate this to D-instantons in type IIB supergravity. By taking the D-instantons to live in an $AdS_5\times S^5$ background, we perform explicit checks of the AdS/CFT correspondence.Comment: 62 pages, typos corrected, table of contents and references adde