Functional analysis of pyochelin-/enantiopyochelin-related genes from a pathogenicity island of Pseudomonas aeruginosa strain PA14.

Genomic islands are foreign DNA blocks inserted in so-called regions of genomic plasticity (RGP). Depending on their gene content, they are classified as pathogenicity, symbiosis, metabolic, fitness or resistance islands, although a detailed functional analysis is often lacking. Here we focused on a 34-kb pathogenicity island of Pseudomonas aeruginosa PA14 (PA14GI-6), which is inserted at RGP5 and carries genes related to those for pyochelin/enantiopyochelin biosynthesis. These enantiomeric siderophores of P. aeruginosa and certain strains of Pseudomonas protegens are assembled by a thiotemplate mechanism from salicylate and two molecules of cysteine. The biochemical function of several proteins encoded by PA14GI-6 was investigated by a series of complementation analyses using mutants affected in potential homologs. We found that PA14_54940 codes for a bifunctional salicylate synthase/salicyl-AMP ligase (for generation and activation of salicylate), that PA14_54930 specifies a dihydroaeruginoic acid (Dha) synthetase (for coupling salicylate with a cysteine-derived thiazoline ring), that PA14_54910 produces a type II thioesterase (for quality control), and that PA14_54880 encodes a serine O-acetyltransferase (for increased cysteine availability). The structure of the PA14GI-6-specified metabolite was determined by mass spectrometry, thin-layer chromatography, and HPLC as (R)-Dha, an iron chelator with antibacterial, antifungal and antitumor activity. The conservation of this genomic island in many clinical and environmental P. aeruginosa isolates of different geographical origin suggests that the ability for Dha production may confer a selective advantage to its host

On the NP-Hardness of Approximating Ordering Constraint Satisfaction Problems

We show improved NP-hardness of approximating Ordering Constraint Satisfaction Problems (OCSPs). For the two most well-studied OCSPs, Maximum Acyclic Subgraph and Maximum Betweenness, we prove inapproximability of $14/15+\epsilon$ and $1/2+\epsilon$. An OCSP is said to be approximation resistant if it is hard to approximate better than taking a uniformly random ordering. We prove that the Maximum Non-Betweenness Problem is approximation resistant and that there are width-$m$ approximation-resistant OCSPs accepting only a fraction $1 / (m/2)!$ of assignments. These results provide the first examples of approximation-resistant OCSPs subject only to P $\neq$ \NP

Flawed Assumptions, Models and Decision Making: Misconceptions Concerning Human Elements in Complex System

The history of high consequence accidents is rich with events wherein the actions, or inaction, of humans was critical to the sequence of events preceding the accident. Moreover, it has been reported that human error may contribute to 80% of accidents, if not more (dougherty and Fragola, 1988). Within the safety community, this reality is widely recognized and there is a substantially greater awareness of the human contribution to system safety today than has ever existed in the past. Despite these facts, and some measurable reduction in accident rates, when accidents do occur, there is a common lament. No matter how hard we try, we continue to have accidents. Accompanying this lament, there is often bewilderment expressed in statements such as, ''There's no explanation for why he/she did what they did''. It is believed that these statements are a symptom of inadequacies in how they think about humans and their role within technological systems. In particular, while there has never been a greater awareness of human factors, conceptual models of human involvement in engineered systems are often incomplete and in some cases, inaccurate

Improving the Coherence Time of Superconducting Coplanar Resonators

The quality factor and energy decay time of superconducting resonators have been measured as a function of material, geometry, and magnetic field. Once the dissipation of trapped magnetic vortices is minimized, we identify surface two-level states (TLS) as an important decay mechanism. A wide gap between the center conductor and the ground plane, as well as use of the superconductor Re instead of Al, are shown to decrease loss. We also demonstrate that classical measurements of resonator quality factor at low excitation power are consistent with single-photon decay time measured using qubit-resonator swap experiments.Comment: 3 pages, 4 figures for the main paper; total 5 pages, 6 figures including supplementary material. Submitted to Applied Physics Letter

Denaturation transition of stretched DNA

We generalize the Poland-Scheraga model to consider DNA denaturation in the presence of an external stretching force. We demonstrate the existence of a force-induced DNA denaturation transition and obtain the temperature-force phase diagram. The transition is determined by the loop exponent $c$ for which we find the new value $c=4\nu-1/2$ such that the transition is second order with $c=1.85<2$ in $d=3$. We show that a finite stretching force $F$ destabilizes DNA, corresponding to a lower melting temperature $T(F)$, in agreement with single-molecule DNA stretching experiments.Comment: 5 pages, 3 figure

Planar Superconducting Resonators with Internal Quality Factors above One Million

We describe the fabrication and measurement of microwave coplanar waveguide resonators with internal quality factors above 10 million at high microwave powers and over 1 million at low powers, with the best low power results approaching 2 million, corresponding to ~1 photon in the resonator. These quality factors are achieved by controllably producing very smooth and clean interfaces between the resonators' aluminum metallization and the underlying single crystal sapphire substrate. Additionally, we describe a method for analyzing the resonator microwave response, with which we can directly determine the internal quality factor and frequency of a resonator embedded in an imperfect measurement circuit.Comment: 4 pages, 3 figures, 1 tabl