457 research outputs found

    D-Branes and Fluxes in Supersymmetric Quantum Mechanics

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    Type 0A string theory in the (2,4k) superconformal minimal model backgrounds, with background ZZ D-branes or R-R fluxes can be formulated non-perturbatively. The branes and fluxes have a description as threshold bound states in an associated one-dimensional quantum mechanics which has a supersymmetric structure, familiar from studies of the generalized KdV system. The relevant bound state wavefunctions in this problem have unusual asymptotics (they are not normalizable in general, and break supersymmetry) which are consistent with the underlying description in terms of open and closed string sectors. The overall organization of the physics is very pleasing: The physics of the closed strings in the background of branes or fluxes is captured by the generalized KdV system and non-perturbative string equations obtained by reduction of that system (the hierarchy of equations found by Dalley, Johnson, Morris and Watterstam). Meanwhile, the bound states wavefunctions, which describe the physics of the ZZ D-brane (or flux) background in interaction with probe FZZT D-branes, are captured by the generalized mKdV system, and non-perturbative string equations obtained by reduction of that system (the Painleve II hierachy found by Periwal and Shevitz in this context).Comment: 41 pages, LaTe

    Antitumor Activity of Selected Derivatives of Pyrazole- Benzenesulfonamides from Dilithiated C(α), N-Phenylhydrazones and Lithiated Methyl 2-(Aminosulfonyl)benzoate

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    Several pyrazole-benzenesulfonamides were subjected to biological evaluation involving tumor formation on potato discs caused by Agrobacterium tumefaciens. This assay led to some excellent and promising initial results with three of the pyrazole compounds showing increased tumor inhibition when compared to a recognized standard, camptothecin. The select pyrazole-benzenesulfonamides were prepared by condensation-cyclization of several dilithiated C(α),N-phenylhydrazones with lithiated methyl 2-aminosulfonyl-benzoate

    Characterising the Canine Oral Microbiome by Direct Sequencing of Reverse-Transcribed rRNA Molecules

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    PCR amplification and sequencing of phylogenetic markers, primarily Small Sub-Unit ribosomal RNA (SSU rRNA) genes, has been the paradigm for defining the taxonomic composition of microbiomes. However, 'universal' SSU rRNA gene PCR primer sets are likely to miss much of the diversity therein. We sequenced a library comprising purified and reverse-transcribed SSU rRNA (RT-SSU rRNA) molecules from the canine oral microbiome and compared it to a general bacterial 16S rRNA gene PCR amplicon library generated from the same biological sample. In addition, we have developed BIONmeta, a novel, open-source, computer package for the processing and taxonomic classification of the randomly fragmented RT-SSU rRNA reads produced. Direct RT-SSU rRNA sequencing revealed that 16S rRNA molecules belonging to the bacterial phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Spirochaetes, were most abundant in the canine oral microbiome (92.5% of total bacterial SSU rRNA). The direct rRNA sequencing approach detected greater taxonomic diversity (1 additional phylum, 2 classes, 1 order, 10 families and 61 genera) when compared with general bacterial 16S rRNA amplicons from the same sample, simultaneously provided SSU rRNA gene inventories of Bacteria, Archaea and Eukarya, and detected significant numbers of sequences not recognised by 'universal' primer sets. Proteobacteria and Spirochaetes were found to be under-represented by PCR-based analysis of the microbiome, and this was due to primer mismatches and taxon-specific variations in amplification efficiency, validated by qPCR analysis of 16S rRNA amplicons from a mock community. This demonstrated the veracity of direct RT-SSU rRNA sequencing for molecular microbial ecology

    Backlund Transformations, D-Branes, and Fluxes in Minimal Type 0 Strings

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    We study the Type 0A string theory in the (2,4k) superconformal minimal model backgrounds, focusing on the fully non-perturbative string equations which define the partition function of the model. The equations admit a parameter, Gamma, which in the spacetime interpretation controls the number of background D-branes, or R-R flux units, depending upon which weak coupling regime is taken. We study the properties of the string equations (often focusing on the (2,4) model in particular) and their physical solutions. The solutions are the potential for an associated Schrodinger problem whose wavefunction is that of an extended D-brane probe. We perform a numerical study of the spectrum of this system for varying Gamma and establish that when Gamma is a positive integer the equations' solutions have special properties consistent with the spacetime interpretation. We also show that a natural solution-generating transformation (that changes Gamma by an integer) is the Backlund transformation of the KdV hierarchy specialized to (scale invariant) solitons at zero velocity. Our results suggest that the localized D-branes of the minimal string theories are directly related to the solitons of the KdV hierarchy. Further, we observe an interesting transition when Gamma=-1.Comment: 17 pages, 3 figure

    Hybrid capture of 964 nuclear genes resolves evolutionary relationships in the mimosoid legumes and reveals the polytomous origins of a large pantropical radiation

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    PREMISE Targeted enrichment methods facilitate sequencing of hundreds of nuclear loci to enhance phylogenetic resolution and elucidate why some parts of the “tree of life” are difficult (if not impossible) to resolve. The mimosoid legumes are a prominent pantropical clade of ~3300 species of woody angiosperms for which previous phylogenies have shown extensive lack of resolution, especially among the species‐rich and taxonomically challenging ingoids. METHODS We generated transcriptomes to select low‐copy nuclear genes, enrich these via hybrid capture for representative species of most mimosoid genera, and analyze the resulting data using de novo assembly and various phylogenomic tools for species tree inference. We also evaluate gene tree support and conflict for key internodes and use phylogenetic network analysis to investigate phylogenetic signal across the ingoids. RESULTS Our selection of 964 nuclear genes greatly improves phylogenetic resolution across the mimosoid phylogeny and shows that the ingoid clade can be resolved into several well‐supported clades. However, nearly all loci show lack of phylogenetic signal for some of the deeper internodes within the ingoids. CONCLUSIONS Lack of resolution in the ingoid clade is most likely the result of hyperfast diversification, potentially causing a hard polytomy of six or seven lineages. The gene set for targeted sequencing presented here offers great potential to further enhance the phylogeny of mimosoids and the wider Caesalpinioideae with denser taxon sampling, to provide a framework for taxonomic reclassification, and to study the ingoid radiation

    Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

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    Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

    Experimental evidence for a light and broad scalar resonance in D+ππ+π+D^+\to \pi^-\pi^+\pi^+ decay

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    From a sample of 1172±611172 \pm 61 D+ππ+π+D^+ \to \pi^- \pi^+ \pi^+ decay, we find Γ(D+ππ+π+)/Γ(D+Kπ+π+)=0.0311±0.00180.0026+0.0016\Gamma (D^+ \to \pi^- \pi^+ \pi^+) / \Gamma (D^+ \to K^- \pi^+ \pi^+) = 0.0311 \pm 0.0018 ^{+0.0016}_{-0.0026}. Using a coherent amplitude analysis to fit the Dalitz plot of this decays, we find strong evidence that a scalar resonance of mass 47823+24±17478^{+24}_{-23} \pm 17 MeV/c2c^2 and width 32440+42±21324^{+42}_{-40} \pm 21 MeV/c2c^2 accounts for approximately half of all decays.Comment: 10 pages, 3 eps figure

    Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

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    Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber
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