The structure of Toho1 β-lactamase in complex with penicillin reveals the role of Tyr105 in substrate recognition

The role of the conserved residue Tyr105 in class A β-lactamases has been the subject of investigation using both structural studies and saturation mutagenesis. Both have shown that while it does not need to be strictly conserved for activity, it is important for substrate recognition. With this in mind we determined the crystal structure of Toho1 β-lactamase at 15 K to 1.10 Å resolution in complex with penicillin. As expected a ring-opened penicillin molecule bound to Ser70 the catalytic nucleophile, can clearly be seen in electron density in the active site. In addition to the trapped penicillin, however, are two additional intact ring-closed penicillin molecules, captured by the enzyme through noncovalent interactions at the edge of the active site

Active-site protonation states in an Acyl-Enzyme intermediate of a Class A β-Lactamase with a Monobactam Substrate

The monobactam antibiotic aztreonam is used to treat cystic fibrosis patients with chronic pulmonary infections colonized by Pseudomonas aeruginosa strains expressing CTX-M extended-spectrum β-lactamases. The protonation states of active-site residues that are responsible for hydrolysis have been determined previously for the apo form of a CTX-M β-lactamase but not for a monobactam acyl-enzyme intermediate. Here we used neutron and high-resolution X-ray crystallography to probe the mechanism by which CTX-M extended-spectrum β-lactamases hydrolyze monobactam antibiotics. In these first reported structures of a class A β-lactamase in an acyl-enzyme complex with aztreonam, we directly observed most of the hydrogen atoms (as deuterium) within the active site. Although Lys 234 is fully protonated in the acyl intermediate, we found that Lys 73 is neutral. These findings are consistent with Lys 73 being able to serve as a general base during the acylation part of the catalytic mechanism, as previously proposed

Shape Invariant Potential and Semi-Unitary Transformations (SUT) for Supersymmetric Harmonic Oscillator in T4-Space

Constructing the Semi - Unitary Transformation (SUT) to obtain the supersymmetric partner Hamiltonians for a one dimensional harmonic oscillator, it has been shown that under this transformation the supersymmetric partner loses its ground state in T^{4}- space while its eigen functions constitute a complete orthonormal basis in a subspace of full Hilbert space. Keywords: Supersymmetry, Superluminal Transformations, Semi Unitary Transformations. PACS No: 14.80L

Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

High speed data acquisition

A general introduction to high speed data acquisition system techniques in modern particle physics experiments is given. Examples are drawn from the SELEX(E78 1) high statistics charmed baryon production and decay experiment now taking data at Fermilab

Measuring the efficiency of Serbian insurance companies

The transition period, and the still ongoing economic crisis, amplify the volatility in the domestic insurance market and forces the management of insurance companies to continuously monitor changes in the market, i.e. to identify risks and opportunities, and therefore to undertake certain activities. The focus of the business of insurance companies is based on satisfying the needs of existing and potential clients. Respecting the current situation in the insurance market in anticipation of future events, the management of insurance companies must create and implement the optimal strategy in line with the company’s capabilities. For this purpose it is necessary to measure the efficiency of the business, which is the subject of this paper where the Data Envelopment Analysis (DEA) method is applied to the case of insurance companies operating in Serbia

Improved Limits on Spin-Dependent WIMP-Proton Interactions from a Two Liter CF3_3I Bubble Chamber

Data from the operation of a bubble chamber filled with 3.5 kg of CF$_{3}$I in a shallow underground site are reported. An analysis of ultrasound signals accompanying bubble nucleations confirms that alpha decays generate a significantly louder acoustic emission than single nuclear recoils, leading to an efficient background discrimination. Three dark matter candidate events were observed during an effective exposure of 28.1 kg-day, consistent with a neutron background. This observation provides the strongest direct detection constraint to date on WIMP-proton spin-dependent scattering for WIMP masses $>20$ GeV/c$^{2}$.Comment: 4 pages, 4 figures V2 submitted to match journal versio

Spin-gravity coupling and gravity-induced quantum phases

External gravitational fields induce phase factors in the wave functions of particles. The phases are exact to first order in the background gravitational field, are manifestly covariant and gauge invariant and provide a useful tool for the study of spin-gravity coupling and of the optics of particles in gravitational or inertial fields. We discuss the role that spin-gravity coupling plays in particular problems.Comment: 18 pages, 1 figur

Measurement of the Ds lifetime

We report precise measurement of the Ds meson lifetime. The data were taken by the SELEX experiment (E781) spectrometer using 600 GeV/c Sigma-, pi- and p beams. The measurement has been done using 918 reconstructed Ds. The lifetime of the Ds is measured to be 472.5 +- 17.2 +- 6.6 fs, using K*(892)0K+- and phi pi+- decay modes. The lifetime ratio of Ds to D0 is 1.145+-0.049.Comment: 5 pages, 2 figures submitted to Phys. Lett.