High allelic diversity in the methyltransferase gene of a phase variable type III restriction-modification system has implications for the fitness of Haemophilus influenzae

Phase variable restriction-modification (R-M) systems are widespread in Eubacteria. Haemophilus influenzae encodes a phase variable homolog of Type III R-M systems. Sequence analysis of this system in 22 non-typeable H.influenzae isolates revealed a hypervariable region in the central portion of the mod gene whereas the res gene was conserved. Maximum likelihood (ML) analysis indicated that most sites outside this hypervariable region experienced strong negative selection but evidence of positive selection for a few sites in adjacent regions. A phylogenetic analysis of 61 Type III mod genes revealed clustering of these H.influenzae mod alleles with mod genes from pathogenic Neisseriae and, based on sequence analysis, horizontal transfer of the mod–res complex between these species. Neisserial mod alleles also contained a hypervariable region and all mod alleles exhibited variability in the repeat tract. We propose that this hypervariable region encodes the target recognition domain (TRD) of the Mod protein and that variability results in alterations to the recognition sequence of this R-M system. We argue that the high allelic diversity and phase variable nature of this R-M system have arisen due to selective pressures exerted by diversity in bacteriophage populations but also have implications for other fitness attributes of these bacterial species

A simulation scenario based mixed integer programming approach to airline reserve crew scheduling under uncertainty

Airlines operate in an uncertain environment for many reasons, for example due to the efects of weather, traffic or crew unavailability (due to delay or sickness). This work focuses on airline reserve crew scheduling under crew absence and journey time uncertainty for an airline operating a single hub and spoke network. Reserve crew can be used to cover absent crew or delayed connecting crew. A fixed number of reserve crew are available for scheduling and each requires a daily standby duty start time. Given an airline's crew schedule and aircraft routings we propose a Mixed Integer Programming approach to scheduling the airline's reserve crew. A simulation of the airline's operations with stochastic journey time and crew absence inputs and without reserve crew is used to generate disruption scenarios for the MIPSSM formulation (Mixed Integer Programming Simulation Scenario Model). Each disruption scenario corresponds to a record of all of the disruptions in a simulation for which reserve crew use would have been beneficial. For each disruption in a disruption scenario there is a record of all reserve crew that could have been used to solve or reduce the disruption. This information forms the input to the MIPSSM formulation, which has the objective of finding the reserve schedule that minimises the overall level of disruption over a set of scenarios. Additionally, modifications of the MIPSSM are explored, and a heuristic solution approach and a reserve use policy derived from the MIPSSM are introduced. A heuristic based on the proposed Mixed Integer Programming Simulation Scenario Model or MIPSSM outperforms a range of alternative approaches. The heuristic solution approach suggests that including the right disruption scenarios is as important as ensuring that enough disruption scenarios are added to the MIPSSM

A simulation scenario based mixed integer programming approach to airline reserve crew scheduling under uncertainty

Airlines operate in an uncertain environment for many reasons, for example due to the efects of weather, traffic or crew unavailability (due to delay or sickness). This work focuses on airline reserve crew scheduling under crew absence and journey time uncertainty for an airline operating a single hub and spoke network. Reserve crew can be used to cover absent crew or delayed connecting crew. A fixed number of reserve crew are available for scheduling and each requires a daily standby duty start time. Given an airline's crew schedule and aircraft routings we propose a Mixed Integer Programming approach to scheduling the airline's reserve crew. A simulation of the airline's operations with stochastic journey time and crew absence inputs and without reserve crew is used to generate disruption scenarios for the MIPSSM formulation (Mixed Integer Programming Simulation Scenario Model). Each disruption scenario corresponds to a record of all of the disruptions in a simulation for which reserve crew use would have been beneficial. For each disruption in a disruption scenario there is a record of all reserve crew that could have been used to solve or reduce the disruption. This information forms the input to the MIPSSM formulation, which has the objective of finding the reserve schedule that minimises the overall level of disruption over a set of scenarios. Additionally, modifications of the MIPSSM are explored, and a heuristic solution approach and a reserve use policy derived from the MIPSSM are introduced. A heuristic based on the proposed Mixed Integer Programming Simulation Scenario Model or MIPSSM outperforms a range of alternative approaches. The heuristic solution approach suggests that including the right disruption scenarios is as important as ensuring that enough disruption scenarios are added to the MIPSSM

A Thirty Kiloparsec Chain of "Beads on a String" Star Formation Between Two Merging Early Type Galaxies in the Core of a Strong-Lensing Galaxy Cluster

New Hubble Space Telescope ultraviolet and optical imaging of the strong-lensing galaxy cluster SDSS J1531+3414 (z=0.335) reveals two centrally dominant elliptical galaxies participating in an ongoing major merger. The interaction is at least somewhat rich in cool gas, as the merger is associated with a complex network of nineteen massive superclusters of young stars (or small tidal dwarf galaxies) separated by ~1 kpc in projection from one another, combining to an estimated total star formation rate of ~5 solar masses per year. The resolved young stellar superclusters are threaded by narrow H-alpha, [O II], and blue excess filaments arranged in a network spanning ~27 kpc across the two merging galaxies. This morphology is strongly reminiscent of the well-known "beads on a string" mode of star formation observed on kpc-scales in the arms of spiral galaxies, resonance rings, and in tidal tails between interacting galaxies. Nevertheless, the arrangement of this star formation relative to the nuclei of the two galaxies is difficult to interpret in a dynamical sense, as no known "beads on a string" systems associated with kpc-scale tidal interactions exhibit such lopsided morphology relative to the merger participants. In this Letter we present the images and follow-up spectroscopy, and discuss possible physical interpretations for the unique arrangement of the young stellar clusters. While we suggest that this morphology is likely to be dynamically short-lived, a more quantitative understanding awaits necessary multiwavelength follow-up, including optical integral field spectroscopy, ALMA sub-mm interferometry, and Chandra X-ray imaging.Comment: 7 pages, 4 figures, accepted for publication in ApJ Letters. High resolution images of the cluster can be found at http://hubblesite.org/news/2014/2

Electrically driven optical interferometry with spins in silicon carbide

Interfacing solid-state defect electron spins to other quantum systems is an ongoing challenge. The ground-state spin's weak coupling to its environment bestows excellent coherence properties, but also limits desired drive fields. The excited-state orbitals of these electrons, however, can exhibit stronger coupling to phononic and electric fields. Here, we demonstrate electrically driven coherent quantum interference in the optical transition of single, basally oriented divacancies in commercially available 4H silicon carbide. By applying microwave frequency electric fields, we coherently drive the divacancy's excited-state orbitals and induce Landau-Zener-Stuckelberg interference fringes in the resonant optical absorption spectrum. Additionally, we find remarkably coherent optical and spin subsystems enabled by the basal divacancy's symmetry. These properties establish divacancies as strong candidates for quantum communication and hybrid system applications, where simultaneous control over optical and spin degrees of freedom is paramount.Comment: 17 pages, 4 figure

High throughput method for analysis of repeat number for 28 phase variable loci of C. jejuni strain NCTC11168

Mutations in simple sequence repeat tracts are a major mechanism of phase variation in several bacterial species including Campylobacter jejuni. Changes in repeat number of tracts located within the reading frame can produce a high frequency of reversible switches in gene expression between ON and OFF states. The genome of C. jejuni strain NCTC11168 contains 29 loci with polyG/polyC tracts of seven or more repeats. This protocol outlines a method for rapidly determining ON/OFF states of these 28 phase-variable loci in a large number of individual colonies. The method combines a series of multiplex PCR assays with a GeneScan assay and automated extraction of tract length, repeat number and expression state. This high throughput, multiplex assay has utility for detecting shifts in phase variation states within and between populations over time and for exploring the effects of phase variation on adaptation to differing selective pressures. An important output of this assay is combinatorial expression states that cannot be determined by other methods. This method can be adapted to analysis of phase variation in other C. jejuni strains and in a diverse range of bacterial species

Variant signal peptides of vaccine antigen, FHbp, impair processing affecting surface localization and antibody-mediated killing in most meningococcal isolates

© Copyright © 2019 da Silva, Karlyshev, Oldfield, Wooldridge, Bayliss, Ryan and Griffin. Meningococcal lipoprotein, Factor H binding protein (FHbp), is the sole antigen of the Trumenba vaccine (Pfizer) and one of four antigens of the Bexsero vaccine (GSK) targeting Neisseria meningitidis serogroup B isolates. Lipidation of FHbp is assumed to occur for all isolates. We show in the majority of a collection of United Kingdom isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) in the signal peptide (SP) of FHbp. A single SNP, common to all, alters a polar amino acid that abolishes processing: lipidation and SP cleavage. Whilst some of the FHbp precursor is retained in the cytoplasm due to reduced binding to SecA, remarkably some is translocated and further surface-localized by Slam. Thus we show Slam is not lipoprotein-specific. In a panel of isolates tested, the overall reduced surface localization of the precursor FHbp, compared to isolates with an intact SP, corresponded with decreased susceptibility to antibody-mediated killing. Our findings shed new light on the canonical pathway for lipoprotein processing and translocation of important relevance for lipoprotein-based vaccines in development and in particular for Trumenba

Sunyaev Zel'dovich Effect Observations of Strong Lensing Galaxy Clusters: Probing the Over-Concentration Problem

We have measured the Sunyaev Zel'dovich (SZ) effect for a sample of ten strong lensing selected galaxy clusters using the Sunyaev Zel'dovich Array (SZA). The SZA is sensitive to structures on spatial scales of a few arcminutes, while the strong lensing mass modeling constrains the mass at small scales (typically < 30"). Combining the two provides information about the projected concentrations of the strong lensing clusters. The Einstein radii we measure are twice as large as expected given the masses inferred from SZ scaling relations. A Monte Carlo simulation indicates that a sample randomly drawn from the expected distribution would have a larger median Einstein radius than the observed clusters about 3% of the time. The implied overconcentration has been noted in previous studies with smaller samples of lensing clusters. It persists for this sample, with the caveat that this could result from a systematic effect such as if the gas fractions of the strong lensing clusters are substantially below what is expected.Comment: submitte

Genomic analysis of serogroup Y Neisseria meningitidis isolates reveals extensive similarities between carriage and disease-associated organisms

Background. Neisseria meningitidis is a frequent colonizer of the human nasopharynx with asymptomatic carriage providing the reservoir for invasive, disease-causing strains. Serogroup Y (MenY) strains are a major cause of meningococcal disease. High resolution genetic analyses of carriage and disease isolates can establish epidemiological relationships and identify potential virulence factors. Methods. Whole genome sequence data were obtained from UK MenY carriage isolates from 1997-2010 (n=99). Sequences were compared to those from MenY invasive isolates from 2010 and 2011 (n=73) using a gene-by-gene approach. Results. Comparisons across 1,605 core genes resolved 91% of isolates into one of eight clusters containing closely related disease and carriage isolates. Six clusters contained carried meningococci isolated in 1997-2001 suggesting temporal stability. One cluster of isolates, predominately sharing the designation Y: P1.5-1,10-1: F4-1: ST-1655 (cc23), was resolved into a sub-cluster with 86% carriage isolates and a second with 90% invasive isolates. These subclusters were defined by specific allelic differences in five core genes encoding glycerate kinase (glxK), valine-pyruvate transaminase (avtA), superoxide dismutase (sodB) and two hypothetical proteins. Conclusions. High resolution genetic analyses detected long-term temporal stability and temporally-overlapping carriage and disease populations for MenY clones but also evidence of a disease-associated clone