A massive high density effective theory

We derive an effective theory for dense, cold and massive quark matter. To this end, we employ a general effective action formalism where antiquarks and quarks far from the Fermi surface, as well as hard gluons, are integrated out explicitly. We show that the resulting effective action depends crucially on the projectors used to separate quarks from antiquarks. If one neglects the quark masses in these projectors, the Feynman rules of the effective theory involve quark mass insertions which connect quark with antiquark propagators. Including the quark masses into these projectors, mass insertions do not appear and the Feynman rules are identical to those found in the zero-mass limit.Comment: 7 pages, 6 figure

The Difficult Case of Crystallization and Structure Solution for the ParC55 Breakage-Reunion Domain of Topoisomerase IV from Streptococcus pneumoniae

BACKGROUND: Streptococcus pneumoniae is the major cause of community-acquired pneumonia and is also associated with bronchitis, meningitis, otitis and sinusitis. The emergence and increasing prevalence of resistance to penicillin and other antibiotics has led to interest in other anti-pneumonococcal drugs such as quinolones that target the enzymes DNA gyrase and topoisomerase IV. During crystallization and in the avenues to finding a method to determine phases for the structure of the ParC55 breakage-reunion domain of topoisomerase IV from Streptococcus pneumoniae, obstacles were faced at each stage of the process. These problems included: majority of the crystals being twinned, either non-diffracting or exhibiting a high mosaic spread. The crystals, which were grown under conditions that favoured diffraction, were difficult to flash-freeze without loosing diffraction. The initial structure solution by molecular replacement failed and the approach proved to be unviable due to the complexity of the problem. In the end the successful structure solution required an in-depth data analysis and a very detailed molecular replacement search. METHODOLOGY/PRINCIPAL FINDINGS: Crystal anti-twinning agents have been tested and two different methods of flash freezing have been compared. The fragility of the crystals did not allow the usual method of transferring the crystals into the heavy atom solution. Consequently, it was necessary to co-crystallize in the presence of the heavy atom compound. The multiple isomorphous replacement approach was unsuccessful because the 7 cysteine mutants which were engineered could not be successfully derivatized. Ultimately, molecular replacement was used to solve the structure by sorting through a large number of solutions in space group P1 using CNS. CONCLUSIONS/SIGNIFICANCE: The main objective of this paper is to describe the obstacles which were faced and overcome in order to acquire data sets on such difficult crystals and determine phases for successful structure solution

Controlled delivery of membrane proteins to artificial lipid bilayers by nystatin-ergosterol modulated vesicle fusion

The study of ion channels and other membrane proteins and their potential use as biosensors and drug screening targets require their reconstitution in an artificial membrane. These applications would greatly benefit from microfabricated devices in which stable artificial lipid bilayers can be rapidly and reliably formed. However, the amount of protein delivered to the bilayer must be carefully controlled. A vesicle fusion technique is investigated where composite ion channels of the polyene antibiotic nystatin and the sterol ergosterol are employed to render protein-carrying vesicles fusogenic After fusion with an ergosterol-free artificial bilayer the nystatin-ergosterol channels do not dissociate immediately and thus cause a transient current signal that marks the vesicle fusion event. Experimental pitfalls of this method were identified, the influence of the nystatin and ergosterol concentration on the fusion rate and the shape of the fusion event marker was explored, and the number of different lipid was reduced. Under these conditions, the B-amyloid peptide could be delivered in a controlled manner to a standard planar bilayer. Additionally, the electrical recordings were obtained of vesicles fusing with a planar lipid bilayer in a microfabricated device, demonstrating the suitability of nystatin-ergosterol modulated vesicle fusion for protein delivery within microsystems

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

Drosophila nuclear lamin precursor Dm0 is translated from either of two developmentally regulated mRNA species apparently encoded by a single gene.

A cDNA clone encoding a portion of Drosophila nuclear lamins Dm1 and Dm2 has been identified by screening a lambda-gt11 cDNA expression library using Drosophila lamin-specific monoclonal antibodies. Two different developmentally regulated mRNA species were identified by Northern blot analysis using the initial cDNA as a probe, and full-length cDNA clones, apparently corresponding to each message, have been isolated. In vitro transcription of both full-length cDNA clones in a pT7 transcription vector followed by in vitro translation in wheat germ lysate suggests that both clones encode lamin Dm0, the polypeptide precursor of lamins Dm1 and Dm2. Nucleotide sequence analyses confirm the impression that both cDNA clones code for the identical polypeptide, which is highly homologous with human lamins A and C as well as with mammalian intermediate filament proteins. The two clones differ in their 3'-untranslated regions. In situ hybridization of lamin cDNA clones to Drosophila polytene chromosomes shows only a single locus of hybridization at or near position 25F on the left arm of chromosome 2. Southern blot analyses of genomic DNA are consistent with the notion that a single or only a few highly similar genes encoding Drosophila nuclear lamin Dm0 exist in the genome

Performance Benchmarking Physical and Virtual Linux Environments

Virtualisation is a method of partitioning one physical computer into multiple “virtual” computers, giving each the appearance and capabilities of running on its own dedicated hardware. Each virtual system functions as a full-fledged computer and can be independently shutdown and restarted. Xen is a form of paravirtualisation developed by the University of Cambridge Computer Laboratory and is available under both a free and commercial license. Performance results comparing Xen to native Linux as well as to other virtualisation tools such as VMWare and User Mode Linux (UML) were published in the paper "Xen and the Art of Virtualization" at the Symposium on Operating Systems Principles in October 2003 by (Barham et al, 2003). (Clark et al, 2004) performed a similar study and produced similar results. In this thesis, a similar performance analysis of Xen is undertaken and also extended to include the performance analysis of OpenVZ, an alternative open source virtualisation technology. This study made explicit use of open-source software and commodity hardware

Interfacial Tensions near Critical Endpoints: Experimental Checks of EdGF Theory

Predictions of the extended de Gennes-Fisher local-functional theory for the universal scaling functions of interfacial tensions near critical endpoints are compared with experimental data. Various observations of the binary mixture isobutyric acid $+$ water are correlated to facilitate an analysis of the experiments of Nagarajan, Webb and Widom who observed the vapor-liquid interfacial tension as a function of {\it both} temperature and density. Antonow's rule is confirmed and, with the aid of previously studied {\it universal amplitude ratios}, the crucial analytic ``background'' contribution to the surface tension near the endpoint is estimated. The residual singular behavior thus uncovered is consistent with the theoretical scaling predictions and confirms the expected lack of symmetry in $(T-T_c)$. A searching test of theory, however, demands more precise and extensive experiments; furthermore, the analysis highlights, a previously noted but surprising, three-fold discrepancy in the magnitude of the surface tension of isobutyric acid $+$ water relative to other systems.Comment: 6 figure

Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase

Type II topoisomerases alter DNA topology to control DNA supercoiling and chromosome segregation and are targets of clinically important anti-infective and anticancer therapeutics. They act as ATP-operated clamps to trap a DNA helix and transport it through a transient break in a second DNA. Here, we present the first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV with a nonhydrolyzable ATP analogue and 14-mer duplex DNA. The ATPase dimer forms a 22 Å protein hole occupied by the kinked DNA bound asymmetrically through positively charged residues lining the hole, and whose mutagenesis impacts the DNA decatenation, DNA relaxation and DNA-dependent ATPase activities of topo IV. These results and a side-bound DNA-ParE structure help explain how the T-segment DNA is captured and transported by a type II topoisomerase, and reveal a new enzyme–DNA interface for drug discovery

Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.

As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from Streptococcus pneumoniae, we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from S. pneumoniae and an 18-base-pair DNA binding site-the E-site-found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo et al. 2005 J. Biol. Chem. 280, 14 252-14 263, doi:10.1074/jbc.M500156200). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of β-lactams and a range of ribosome-bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site

Ward's Hierarchical Clustering Method: Clustering Criterion and Agglomerative Algorithm

The Ward error sum of squares hierarchical clustering method has been very widely used since its first description by Ward in a 1963 publication. It has also been generalized in various ways. However there are different interpretations in the literature and there are different implementations of the Ward agglomerative algorithm in commonly used software systems, including differing expressions of the agglomerative criterion. Our survey work and case studies will be useful for all those involved in developing software for data analysis using Ward's hierarchical clustering method.Comment: 20 pages, 21 citations, 4 figure