GyrI: a counter-defensive strategy against proteinaceous inhibitors of DNA gyrase

DNA gyrase is the target of two plasmid-encoded toxins CcdB and microcin B17, which ensure plasmid maintenance. These proteins stabilize gyrase-DNA covalent complexes leading to double-strand breaks in the genome. In contrast, the physiological role of chromosomally encoded inhibitor of DNA gyrase (Gyrl) in Escherichia coli is unclear and its mechanism of inhibition has not been established. We demonstrate that the mode of inhibition of GyrI is distinct from all other gyrase inhibitors. It inhibits DNA gyrase prior to, or at the step of, binding of DNA by the enzyme. Gyrl reduces intrinsic as well as toxin-stabilized gyrase-DNA covalent complexes. Furthermore, Gyri reduces microcin B17-mediated double-strand breaks in vivo, imparting protection to the cells against the toxin, substantiating the in vitro results. Thus, Gyrl is an antidote to DNA gyrase-specific proteinaceous poisons encoded by plasmid addiction systems.

Incentive compatible mechanisms for group ticket allocation in software maintenance services

A customer reported problem (or Trouble Ticket) in software maintenance is typically solved by one or more maintenance engineers. The decision of allocating the ticket to one or more engineers is generally taken by the lead, based on customer delivery deadlines and a guided complexity assessment from each maintenance engineer. The key challenge in such a scenario is two folds, un-truthful (hiked up) elicitation of ticket complexity by each engineer to the lead and the decision of allocating the ticket to a group of engineers who will solve the ticket with in customer deadline. The decision of allocation should ensure Individual and Coalitional Rationality along with Coalitional Stability. In this paper we use game theory to examine the issue of truthful elicitation of ticket complexities by engineers for solving ticket as a group given a specific customer delivery deadline. We formulate this problem as strategic form game and propose two mechanisms, (1) Division of Labor (DOL) and (2) Extended Second Price (ESP). In the proposed mechanisms we show that truth telling by each engineer constitutes a Dominant Strategy Nash Equilibrium of the underlying game. Also we analyze the existence of Individual Rationality (IR) and Coalitional Rationality (CR) properties to motivate voluntary and group participation. We use Core, solution concept from co-operative game theory to analyze the stability of the proposed group based on the allocation and payments.

Inhibition of the Interaction Between NS3 Protease and HCV IRES With a Small Peptide: A Novel Therapeutic Strategy

Recently, we have demonstrated that the protease domain of NS3 alone can bind specifically to hepatitis C virus (HCV) internal ribosome entry site (IRES) near the initiator AUG, dislodges human La protein and inhibits translation in favor of viral RNA replication. Here, by using a computational approach, the contact points of the protease on the HCV IRES were putatively mapped. A 30-mer NS3 peptide was designed from the predicted RNA-binding region that retained RNA-binding ability and also inhibited IRES-mediated translation. This peptide was truncated to 15 mer and this also demonstrated ability to inhibit HCV RNA-directed translation as well as replication. More importantly, its activity was tested in an in vivo mouse model by encapsulating the peptide in Sendai virus virosomes followed by intravenous delivery. The study demonstrates for the first time that the HCV NS3-IRES RNA interaction can be selectively inhibited using a small peptide and reports a strategy to deliver the peptide into the liver.

Make or buy decision in the context of manufacturing strategy

This paper describes an approach to structuring the make or buy decision process, basing it firmly in the context of an overall manufacturing strategy. The work has been carried out jointly by the University of Cambridge Manufacturing Engineering Group and Lucas Industries. A review of the current state of ideas surrounding the linked issues of vertical integration and make or buy decisions is presented. Important features of the approach include identification of core manufacturing capabilities, assessment of the role of technology in manufacturing, the development of a cost model to support make or buy decisions and a review of the strategic implications of varying degrees of vertical integration.

Harmful algal research and response: A human dimensions strategy

Harmful Algal Research and Response: A Human Dimensions Strategy (HARR-HD) justifies and guides a coordinated national commitment to human dimensions research critical to prevent and respond to impacts of harmful algal blooms (HABs). Beyond HABs, it serves as a framework for developing hu-man dimensions research as a cross-cutting priority of ecosystem science supporting coastal and ocean management, including hazard research and mitigation planning. Measuring and promoting commu-nity resilience to hazards require human dimensions research outcomes such as effective risk commu-nication strategies; assessment of community vulnerability; identification of susceptible populations; comprehensive assessment of environmental, sociocultural, and economic impacts; development of effective decision support tools; and improved coordination among agencies and stakeholders. HARR-HD charts a course for human dimensions research to achieve these and other priorities through co-ordinated implementation by the Joint Subcommittee on Ocean Science and Technology (JSOST) In-teragency Working Group on HABs, Hypoxia and Human Health (IWG-4H); national HAB funding programs; national research and response programs; and state research and monitoring programs. (PDF contains 72 pages)

STREAM Country Strategy Paper: Sri Lanka

In Sri Lanka the incidence of poverty varies among regions and livelihoods; aquatic resources users represent a poor category in many regions and therefore a vulnerable group. In December 2004 the country was hit by a Tsunami originating off the coast of Aceh in Indonesia, which affected the livelihoods of a large section of coastal aquatic resource users. The country is currently engaged in a major humanitarian effort to improve the livelihoods of aquatic resources users through various donor-funded projects. (PDF contains 18 pages)

Forage strategy of juvenile Lates niloticus (L.) in Lake Victoria, Kenya

Six KMFRI stations located in Nyanza Gulf of Lake Victoria (Kenya) were sampled in order to investigate the forage strategy of juvenile Lates niloticus. Thirty speciemens were collected using a bottom trawl at each station and sorted into three size classes 1-2 cm and 3-20 cm total length. Stomach contents were analysed and taxonomic keys used to identify zoplankton and other insects. Caridina nilotica was the dominant food item in both frequency of occurrence and numerical abundance. In fish examined from 1-2 cm T.L., cladocerans were prominent food items, while at 2-3 and 3-20 cm, C. nilotica was dominant

Simple Coalitional Strategy Profiles in Repeated Games

This paper is a version of the discussion paper titled "Simple coalitional strategy profiles"

Applications of a Concise and General Strategy for the Syntheses of Transtaganolide and Basiliolide Natural Products

Herein are described the total syntheses of all members of the transtaganolide and basiliolide natural product family. Utilitzation of an Ireland–Claisen rearrangement/Diels–Alder cycloaddition cascade (ICR/DA) allowed for rapid assembly of the transtaganolide and basiliolide oxabicyclo[2.2.2]octane core. This methodology is general and was applicable to all members of the natural product family.

A brief introduction outlines all the synthetic progress previously disclosed by Lee, Dudley, and Johansson. This also includes the initial syntheses of transtaganolides C and D, as well as basiliolide B and epi-basiliolide B accomplished by Stoltz in 2011. Lastly, we discuss our racemic synthesis of basililide C and epi-basiliolide C, which utilized an ICR/DA cascade to constuct the oxabicyclo[2.2.2]octane core and formal [5+2] annulation to form the ketene-acetal containing 7-membered C-ring.

Next, we describe a strategy for an asymmetric ICR/DA cascade, by incorporation of a chiral silane directing group. This allowed for enantioselective construction of the C8 all-carbon quaternary center formed in the Ireland–Claisen rearrangement. Furthermore, a single hydride reduction and subsequent translactonization of a C4 methylester bearing oxabicyclo[2.2.2]octane core demonstrated a viable strategy for the desired skeletal rearrangement to obtain pentacyclic transtaganolides A and B. Application of the asymmetric strategy culminated in the total syntheses of (–)-transtaganolide A, (+)-transtaganolide B, (+)-transtaganolide C, and (–)-transtaganolide D. Comparison of the optical rotation data of the synthetically derived transtaganolides to that from the isolated counterparts has overarching biosynthetic implications which are discussed.

Lastly, improvement to the formal [5+2] annulation strategy is described. Negishi cross-coupling of methoxyethynyl zinc chloride using a palladium Xantphos catalyst is optimized for iodo-cyclohexene. Application of this technology to an iodo-pyrone geranyl ester allowed for formation and isolation of the eneyne product. Hydration of the enenye product forms natural metabolite basiliopyrone. Furthermore, the eneyne product can undergo an ICR/DA cascade and form transtaganolides C and D in a single step from an achiral monocyclic precursor.