990 research outputs found

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

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    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

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    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

    Measuring the efficiency of Serbian insurance companies

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    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

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    Data from the operation of a bubble chamber filled with 3.5 kg of CF3_{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>20 GeV/c2^{2}.Comment: 4 pages, 4 figures V2 submitted to match journal versio

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

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    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

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    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

    Supersymmetrization of Quaternion Dirac Equation for Generalized Fields of Dyons

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    The quaternion Dirac equation in presence of generalized electromagnetic field has been discussed in terms of two gauge potentials of dyons. Accordingly, the supersymmetry has been established consistently and thereafter the one, two and component Dirac Spinors of generalized quaternion Dirac equation of dyons for various energy and spin values are obtained for different cases in order to understand the duality invariance between the electric and magnetic constituents of dyons.Comment: Key words: Supersymmetry, quaternion, Dirac equation, dyons PACS No.: 11.30.Pb, 14.80.Ly, 03.65.G

    Power Spectrum Analysis of Physikalisch-Technische Bundesanstalt Decay-Rate Data: Evidence for Solar Rotational Modulation

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    Evidence for an anomalous annual periodicity in certain nuclear decay data has led to speculation concerning a possible solar influence on nuclear processes. We have recently analyzed data concerning the decay rates of Cl-36 and Si-32, acquired at the Brookhaven National Laboratory (BNL), to search for evidence that might be indicative of a process involving solar rotation. Smoothing of the power spectrum by weighted-running-mean analysis leads to a significant peak at frequency 11.18/yr, which is lower than the equatorial synodic rotation rates of the convection and radiative zones. This article concerns measurements of the decay rates of Ra-226 acquired at the Physikalisch-Technische Bundesanstalt (PTB) in Germany. We find that a similar (but not identical) analysis yields a significant peak in the PTB dataset at frequency 11.21/yr, and a peak in the BNL dataset at 11.25/yr. The change in the BNL result is not significant since the uncertainties in the BNL and PTB analyses are estimated to be 0.13/yr and 0.07/yr, respectively. Combining the two running means by forming the joint power statistic leads to a highly significant peak at frequency 11.23/yr. We comment briefly on the possible implications of these results for solar physics and for particle physics.Comment: 15 pages, 13 figure

    Spontaneous Diabetes in Hemizygous Human Amylin Transgenic Mice That Developed Neither Islet Amyloid nor Peripheral Insulin Resistance

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    OBJECTIVES—We sought to 1) Determine whether soluble-misfolded amylin or insoluble-fibrillar amylin may cause or result from diabetes in human amylin transgenic mice and 2) determine the role, if any, that insulin resistance might play in these processes
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