Towards an improved understanding of eta --> gamma^* gamma^*

We argue that high-quality data on the reaction $e^+e^-\to \pi^+\pi^-\eta$ will allow one to determine the double off-shell form factor $\eta \to \gamma^*\gamma^*$ in a model-independent way with controlled accuracy. This is an important step towards a reliable evaluation of the hadronic light-by-light scattering contribution to the anomalous magnetic moment of the muon. When analyzing the existing data for $e^+e^- \to \pi^+\pi^-\eta$ in the range of total energies $1\text{GeV}^2<Q_2^2<(4.5\text{GeV})^2$, we demonstrate that the double off-shell form factor $F_{\eta\gamma^*\gamma^*}(Q_1^2,Q_2^2)$ is consistent with the commonly employed factorization ansatz at least for $Q_1^2<1\text{GeV}^2$, if the effect of the $a_2$ meson is taken into account. However, better data are needed to draw firm conclusions.Comment: 7 pages, 3 figure

Kinetic and Spectroscopic Characterization of the H178A Methionyl Aminopeptidase from \u3cem\u3eEscherichia coli\u3c/em\u3e

To gain insight into the role of the strictly conserved histidine residue, H178, in the reaction mechanism of the methionyl aminopeptidase from Escherichia coli (EcMetAP-I), the H178A mutant enzyme was prepared. Metal-reconstituted H178A binds only one equivalent of Co(II) or Fe(II) tightly with affinities that are identical to the WT enzyme based on kinetic and isothermal titration calorimetry (ITC) data. Electronic absorption spectra of Co(II)-loaded H178A EcMetAP-I indicate that the active site divalent metal ion is pentacoordinate, identical to the WT enzyme. These data indicate that the metal binding site has not been affected by altering H178. The effect of altering H178 on activity is, in general, due to a decrease in kcat. The kcat value for Co(II)-loaded H178A decreased 70-fold toward MGMM and 290-fold toward MP-p-NA compared to the WT enzyme, while kcat decreased 50-fold toward MGMM for the Fe(II)-loaded H178A enzyme and 140-fold toward MP-p-NA. The Km values for MGMM remained unaffected, while those for MP-p-NA increased approximately 2-fold for Co(II)- and Fe(II)-loaded H178A. The kcat/Km values for both Co(II)- and Fe(II)-loaded H178A toward both substrates ranged from ∼50- to 580-fold reduction. The pH dependence of log Km, log kcat, and log(kcat/Km) of both WT and H178A EcMetAP-I were also obtained and are identical, within error, for H178A and WT EcMetAP-I. Therefore, H178A is catalytically important but is not required for catalysis. Assignment of one of the observed pKa values at 8.1 for WT EcMetAP-I was obtained from plots of molar absorptivity at λmax(640) vs pH for both WT and H178A EcMetAP-I. Apparent pKa values of 8.1 and 7.6 were obtained for WT and H178A EcMetAP-I, respectively, and were assigned to the deprotonation of a metal-bound water molecule. The data reported herein provide support for the key elements of the previously proposed mechanism and suggest that a similar mechanism can apply to the enzyme with a single metal in the active site

Torsion Degrees of Freedom in the Regge Calculus as Dislocations on the Simplicial Lattice

Using the notion of a general conical defect, the Regge Calculus is generalized by allowing for dislocations on the simplicial lattice in addition to the usual disclinations. Since disclinations and dislocations correspond to curvature and torsion singularities, respectively, the method we propose provides a natural way of discretizing gravitational theories with torsion degrees of freedom like the Einstein-Cartan theory. A discrete version of the Einstein-Cartan action is given and field equations are derived, demanding stationarity of the action with respect to the discrete variables of the theory

The Dimerization Domain in DapE Enzymes Is Required for Catalysis

The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,Ldiaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate

Regge Calculus in Teleparallel Gravity

In the context of the teleparallel equivalent of general relativity, the Weitzenbock manifold is considered as the limit of a suitable sequence of discrete lattices composed of an increasing number of smaller an smaller simplices, where the interior of each simplex (Delaunay lattice) is assumed to be flat. The link lengths between any pair of vertices serve as independent variables, so that torsion turns out to be localized in the two dimensional hypersurfaces (dislocation triangle, or hinge) of the lattice. Assuming that a vector undergoes a dislocation in relation to its initial position as it is parallel transported along the perimeter of the dual lattice (Voronoi polygon), we obtain the discrete analogue of the teleparallel action, as well as the corresponding simplicial vacuum field equations.Comment: Latex, 10 pages, 2 eps figures, to appear in Class. Quant. Gra

How black holes get their kicks: Gravitational radiation recoil revisited

Gravitational waves from the coalescence of binary black holes carry away linear momentum, causing center of mass recoil. This "radiation rocket" effect has important implications for systems with escape speeds of order the recoil velocity. We revisit this problem using black hole perturbation theory, treating the binary as a test mass spiraling into a spinning hole. For extreme mass ratios (q = m1/m2 << 1) we compute the recoil for the slow inspiral epoch of binary coalescence very accurately; these results can be extrapolated to q ~ 0.4 with modest accuracy. Although the recoil from the final plunge contributes significantly to the final recoil, we are only able to make crude estimates of its magnitude. We find that the recoil can easily reach ~ 100-200 km/s, but most likely does not exceed ~ 500 km/s. Though much lower than previous estimates, this recoil is large enough to have important astrophysical consequences. These include the ejection of black holes from globular clusters, dwarf galaxies, and high-redshift dark matter halos.Comment: 4 pages, 2 figures, emulateapj style; minor changes made; accepted to ApJ Letter

Practical Spectrophotometric Assay for the \u3cem\u3edapE\u3c/em\u3e-Encoded \u3cem\u3eN\u3c/em\u3e-Succinyl-L,L-Diaminopimelic Acid Desuccinylase, a Potential Antibiotic Target

A new enzymatic assay for the bacterial enzyme succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) is described. This assay employs N6-methyl-N2-succinyl-L,L-diaminopimelic acid (N6-methyl-L,L-SDAP) as the substrate with ninhydrin used to detect cleavage of the amide bond of the modified substrate, wherein N6-methylation enables selective detection of the primary amine enzymatic product. Molecular modeling supported preparation of the mono-N6-methylated-L,L-SDAP as an alternate substrate for the assay, given binding in the active site of DapE predicted to be comparable to the endogenous substrate. The alternate substrate for the assay, N6-methyl-L,L-SDAP, was synthesized from the tert-butyl ester of Boc-L-glutamic acid employing a Horner-Wadsworth-Emmons olefination followed by an enantioselective reduction employing Rh(I)(COD)(S,S)-Et-DuPHOS as the chiral catalyst. Validation of the new ninhydrin assay was demonstrated with known inhibitors of DapE from Haemophilus influenza (HiDapE) including captopril (IC50 = 3.4 [± 0.2] μM, 3-mercaptobenzoic acid (IC50 = 21.8 [±2.2] μM, phenylboronic acid (IC50 = 316 [± 23.6] μM, and 2-thiopheneboronic acid (IC50 = 111 [± 16] μM. Based on these data, this assay is simple and robust, and should be amenable to high-throughput screening, which is an important step forward as it opens the door to medicinal chemistry efforts toward the discovery of DapE inhibitors that can function as a new class of antibiotics

Strong Gravitational Lensing by Sgr A*

In recent years, there has been increasing recognition of the potential of the galactic center as a probe of general relativity in the strong field. There is almost certainly a black hole at Sgr A* in the galactic center, and this would allow us the opportunity to probe dynamics near the exterior of the black hole. In the last decade, there has been research into extreme gravitational lensing in the galactic center. Unlike in most applications of gravitational lensing, where the bending angle is of the order of several arc seconds, very large bending angles are possible for light that closely approaches a black hole. Photons may even loop multiple times around a black hole before reaching the observer. There have been many proposals to use light's close approach to the black hole as a probe of the black hole metric. Of particular interest is the property of light lensed by the S stars orbiting in the galactic center. This paper will review some of the attempts made to study extreme lensing as well as extend the analysis of lensing by S stars. In particular, we are interested in the effect of a Reissner-Nordstrom like 1/r^2 term in the metric and how this would affect the properties of relativistic images.Comment: 13 pages, 9 figures. Submitted as invited review article for the GR19 issue of CQ

Cosmology with coalescing massive black holes

The gravitational waves generated in the coalescence of massive binary black holes will be measurable by LISA to enormous distances. Redshifts z~10 or larger (depending somewhat on the mass of the binary) can potentially be probed by such measurements, suggesting that binary coalescences can be made into cosmological tools. We discuss two particularly interesting types of probes. First, by combining gravitational-wave measurements with information about the universe's cosmography, we can study the evolution of black hole masses and merger rates as a function of redshift, providing information about the growth of structures at high redshift and possibly constraining hierarchical merger scenarios. Second, if it is possible to associate an ``electromagnetic'' counterpart with a coalescence, it may be possible to measure both redshift and luminosity distance to an event with less than ~1% error. Such a measurement would constitute an amazingly precise cosmological standard candle. Unfortunately, gravitational lensing uncertainties will reduce the quality of this candle significantly. Though not as amazing as might have been hoped, such a candle would nonetheless very usefully complement other distance-redshift probes, in particular providing a valuable check on systematic effects in such measurements.Comment: 8 pages, 4 figure