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

Shifts and widths of collective excitations in trapped Bose gases by the dielectric formalism

We present predictions for the temperature dependent shifts and damping rates. They are obtained by applying the dielectric formalism to a simple model of a trapped Bose gas. Within the framework of the model we use lowest order perturbation theory to determine the first order correction to the results of Hartree-Fock-Bogoliubov-Popov theory for the complex collective excitation frequencies, and present numerical results for the temperature dependence of the damping rates and the frequency shifts. Good agreement with the experimental values measured at JILA are found for the m=2 mode, while we find disagreements in the shifts for m=0. The latter point to the necessity of a non-perturbative treatment for an explanation of the temperature-dependence of the m=0 shifts.Comment: 10 pages revtex, 3 figures in postscrip

Energies and damping rates of elementary excitations in spin-1 Bose-Einstein condensed gases

Finite temperature Green's function technique is used to calculate the energies and damping rates of elementary excitations of the homogeneous, dilute, spin-1 Bose gases below the Bose-Einstein condensation temperature both in the density and spin channels. For this purpose the self-consistent dynamical Hartree-Fock model is formulated, which takes into account the direct and exchange processes on equal footing by summing up certain classes of Feynman diagrams. The model is shown to fulfil the Goldstone theorem and to exhibit the hybridization of one-particle and collective excitations correctly. The results are applied to the gases of ^{23}Na and ^{87}Rb atoms.Comment: 26 pages, 21 figures. Added 2 new figures, detailed discussio

Thermodynamics of a Trapped Bose-Fermi Mixture

By using the Hartree-Fock-Bogoliubov equations within the Popov approximation, we investigate the thermodynamic properties of a dilute binary Bose-Fermi mixture confined in an isotropic harmonic trap. For mixtures with an attractive Bose-Fermi interaction we find a sizable enhancement of the condensate fraction and of the critical temperature of Bose-Einstein condensation with respect to the predictions for a pure interacting Bose gas. Conversely, the influence of the repulsive Bose-Fermi interaction is less pronounced. The possible relevance of our results in current experiments on trapped $^{87}{\rm Rb}-^{40}${\rm K} mixtures is discussed.Comment: 5 pages + 4 figures; minor changes, final version to appear in Phys. Rev. A; the extension work on the finite-temperature low-lying excitations can be found in cond-mat/030763

Equilibrium and dynamical properties of two dimensional self-gravitating systems

A system of N classical particles in a 2D periodic cell interacting via long-range attractive potential is studied. For low energy density $U$ a collapsed phase is identified, while in the high energy limit the particles are homogeneously distributed. A phase transition from the collapsed to the homogeneous state occurs at critical energy U_c. A theoretical analysis within the canonical ensemble identifies such a transition as first order. But microcanonical simulations reveal a negative specific heat regime near $U_c$. The dynamical behaviour of the system is affected by this transition : below U_c anomalous diffusion is observed, while for U > U_c the motion of the particles is almost ballistic. In the collapsed phase, finite $N$-effects act like a noise source of variance O(1/N), that restores normal diffusion on a time scale diverging with N. As a consequence, the asymptotic diffusion coefficient will also diverge algebraically with N and superdiffusion will be observable at any time in the limit N \to \infty. A Lyapunov analysis reveals that for U > U_c the maximal exponent \lambda decreases proportionally to N^{-1/3} and vanishes in the mean-field limit. For sufficiently small energy, in spite of a clear non ergodicity of the system, a common scaling law \lambda \propto U^{1/2} is observed for any initial conditions.Comment: 17 pages, Revtex - 15 PS Figs - Subimitted to Physical Review E - Two column version with included figures : less paper waste

Bose condensates in a harmonic trap near the critical temperature

The mean-field properties of finite-temperature Bose-Einstein gases confined in spherically symmetric harmonic traps are surveyed numerically. The solutions of the Gross-Pitaevskii (GP) and Hartree-Fock-Bogoliubov (HFB) equations for the condensate and low-lying quasiparticle excitations are calculated self-consistently using the discrete variable representation, while the most high-lying states are obtained with a local density approximation. Consistency of the theory for temperatures through the Bose condensation point requires that the thermodynamic chemical potential differ from the eigenvalue of the GP equation; the appropriate modifications lead to results that are continuous as a function of the particle interactions. The HFB equations are made gapless either by invoking the Popov approximation or by renormalizing the particle interactions. The latter approach effectively reduces the strength of the effective scattering length, increases the number of condensate atoms at each temperature, and raises the value of the transition temperature relative to the Popov approximation. The renormalization effect increases approximately with the log of the atom number, and is most pronounced at temperatures near the transition. Comparisons with the results of quantum Monte Carlo calculations and various local density approximations are presented, and experimental consequences are discussed.Comment: 15 pages, 11 embedded figures, revte

Indoline‐6‐Sulfonamide Inhibitors of the Bacterial Enzyme DapE

Inhibitors of the bacterial enzyme dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE; EC 3.5.1.18) hold promise as antibiotics with a new mechanism of action. Herein we describe the discovery of a new series of indoline sulfonamide DapE inhibitors from a high-throughput screen and the synthesis of a series of analogs. Inhibitory potency was measured by a ninhydrin-based DapE assay recently developed by our group. Molecular docking experiments suggest active site binding with the sulfonamide acting as a zinc-binding group (ZBG)

Hamiltonian Cycle Parameterized by Treedepth in Single Exponential Time and Polynomial Space

For many algorithmic problems on graphs of treewidth $t$, a standard dynamic programming approach gives an algorithm with time and space complexity $2^{\mathcal{O}(t)}\cdot n^{\mathcal{O}(1)}$. It turns out that when one considers the more restrictive parameter treedepth, it is often the case that a variation of this technique can be used to reduce the space complexity to polynomial, while retaining time complexity of the form $2^{\mathcal{O}(d)}\cdot n^{\mathcal{O}(1)}$, where $d$ is the treedepth. This transfer of methodology is, however, far from automatic. For instance, for problems with connectivity constraints, standard dynamic programming techniques give algorithms with time and space complexity $2^{\mathcal{O}(t\log t)}\cdot n^{\mathcal{O}(1)}$ on graphs of treewidth $t$, but it is not clear how to convert them into time-efficient polynomial space algorithms for graphs of low treedepth. Cygan et al. (FOCS'11) introduced the Cut&Count technique and showed that a certain class of problems with connectivity constraints can be solved in time and space complexity $2^{\mathcal{O}(t)}\cdot n^{\mathcal{O}(1)}$. Recently, Hegerfeld and Kratsch (STACS'20) showed that, for some of those problems, the Cut&Count technique can be also applied in the setting of treedepth, and it gives algorithms with running time $2^{\mathcal{O}(d)}\cdot n^{\mathcal{O}(1)}$ and polynomial space usage. However, a number of important problems eluded such a treatment, with the most prominent examples being Hamiltonian Cycle and Longest Path. In this paper we clarify the situation by showing that Hamiltonian Cycle, Hamiltonian Path, Long Cycle, Long Path, and Min Cycle Cover all admit $5^d\cdot n^{\mathcal{O}(1)}$-time and polynomial space algorithms on graphs of treedepth $d$. The algorithms are randomized Monte Carlo with only false negatives.Comment: Presented at WG2020. 20 pages, 2 figure

The transverse breathing mode of an elongated Bose-Einstein condensate

We study experimentally the transverse monopole mode of an elongated rubidium condensate. Due to the scaling invariance of the non-linear Schr\"odinger (Gross-Pitaevski) equation, the oscillation is monochromatic and sinusoidal at short times, even under strong excitation. For ultra-low temperatures, the quality factor $Q=\omega_0/\gamma_0$ can exceed 2000, where $\omega_0$ and $\gamma_0$ are the mode angular frequency and damping rate. This value is much larger than any previously reported for other eigenmodes of a condensate. We also present the temperature variation of $\omega_0$ and $\gamma_0$.Comment: 4 pages, 4 figures, submitted to PR

Finite temperature excitations of a trapped Bose-Fermi mixture

We present a detailed study of the low-lying collective excitations of a spherically trapped Bose-Fermi mixture at finite temperature in the collisionless regime. The excitation frequencies of the condensate are calculated self-consistently using the static Hartree-Fock-Bogoliubov theory within the Popov approximation. The frequency shifts and damping rates due to the coupled dynamics of the condensate, noncondensate, and degenerate Fermi gas are also taken into account by means of the random phase approximation and linear response theory. In our treatment, the dipole excitation remains close to the bare trapping frequency for all temperatures considered, and thus is consistent with the generalized Kohn theorem. We discuss in some detail the behavior of monopole and quadrupole excitations as a function of the Bose-Fermi coupling. At nonzero temperatures we find that, as the mixture moves towards spatial separation with increasing Bose-Fermi coupling, the damping rate of the monopole (quadrupole) excitation increases (decreases). This provides us a useful signature to identify the phase transition of spatial separation.Comment: 10 pages, 8 figures embedded; to be published in Phys. Rev.