An ambitwistor string field theory approach to supergravity

In this thesis a covariant closed superstring field theory, equivalent to classical ten-dimensional Type II supergravity, is presented. The defining conformal field theory is the ambitwistor string worldsheet theory of Mason and Skinner [1]. This theory is known to reproduce the scattering amplitudes of Cachazo, He and Yuan [2] in which the scattering equations play an important role and our ambitwistor string field theory naturally incorporates these results. We present the operator formalism description of the ambitwsitor string and propose an action for the string field theory of the bosonic and supersymmetric theories. The correct linearised gauge symmetries and spacetime actions are explicitly reproduced and evidence is given that the action is correct to all orders. The focus is on the Neveu-Schwarz sector and the explicit description of tree level perturbation theory about flat spacetime. This thesis is fully based in our published paper [3] and so has a considerable overlap with it

Darboux-Kadomtsev-Petviashvili system as an integrable Chern-Simons multiform theory in infinite dimensional space

The Darboux-Kadomtsev-Petviashvili system is a universal three-dimensional integrable field theory, which is a generating system for the entire Kadomtsev-Petviashvili hierarchy, and at the same time generalizes the Darboux system, describing orthogonal curvilinear coordinates. In this paper, we establish a hierarchy of Lagrangian multiforms for the Darboux-Kadomtsev-Petviashvili system, derived from a hierarchy of Chern-Simons actions in an infinite-dimensional space of Miwa variables. This provides an integrable variational description of this multidimensionally consistent field theory embedded in infinite dimensional space

Sequence and analysis of the genome of the pathogenic yeast Candida orthopsilosis

Candida orthopsilosis is closely related to the fungal pathogen Candida parapsilosis. However, whereas C. parapsilosis is a major cause of disease in immunosuppressed individuals and in premature neonates, C. orthopsilosis is more rarely associated with infection. We sequenced the C. orthopsilosis genome to facilitate the identification of genes associated with virulence. Here, we report the de novo assembly and annotation of the genome of a Type 2 isolate of C. orthopsilosis. The sequence was obtained by combining data from next generation sequencing (454 Life Sciences and Illumina) with paired-end Sanger reads from a fosmid library. The final assembly contains 12.6 Mb on 8 chromosomes. The genome was annotated using an automated pipeline based on comparative analysis of genomes of Candida species, together with manual identification of introns. We identified 5700 protein-coding genes in C. orthopsilosis, of which 5570 have an ortholog in C. parapsilosis. The time of divergence between C. orthopsilosis and C. parapsilosis is estimated to be twice as great as that between Candida albicans and Candida dubliniensis. There has been an expansion of the Hyr/Iff family of cell wall genes and the JEN family of monocarboxylic transporters in C. parapsilosis relative to C. orthopsilosis. We identified one gene from a Maltose/Galactoside O-acetyltransferase family that originated by horizontal gene transfer from a bacterium to the common ancestor of C. orthopsilosis and C. parapsilosis. We report that TFB3, a component of the general transcription factor TFIIH, undergoes alternative splicing by intron retention in multiple Candida species. We also show that an intein in the vacuolar ATPase gene VMA1 is present in C. orthopsilosis but not C. parapsilosis, and has a patchy distribution in Candida species. Our results suggest that the difference in virulence between C. parapsilosis and C. orthopsilosis may be associated with expansion of gene families

A superstring field theory for supergravity

Abstract A covariant closed superstring field theory, equivalent to classical tendimensional Type II supergravity, is presented. The defining conformal field theory is the ambitwistor string worldsheet theory of Mason and Skinner. This theory is known to reproduce the scattering amplitudes of Cachazo, He and Yuan in which the scattering equations play an important role and the string field theory naturally incorporates these results. We investigate the operator formalism description of the ambitwsitor string and propose an action for the string field theory of the bosonic and supersymmetric theories. The correct linearised gauge symmetries and spacetime actions are explicitly reproduced and evidence is given that the action is correct to all orders. The focus is on the NeveuSchwarz sector and the explicit description of tree level perturbation theory about flat spacetime. Application of the string field theory to general supergravity backgrounds and the inclusion of the Ramond sector are briefly discussed

The Darboux-KP system as an integrable Chern-Simons multiform theory in infinite dimensional space

In a previous paper by one of the authors, a Lagrangian 3-form structure was established for a generalised Darboux system, originally describing orthogonal curvilinear coordinate systems, which encodes the Kadomtsev-Petviashvili (KP) hierarchy. Here a hierarchy of Lagrangian multiforms is established for the same system, viewed as a hierarchy of Chern-Simons actions in an infinite-dimensional space of Miwa variables, constituting the variational form of a universal 3D integrable system embedded in this infinite-dimensional space

Increasing the performance of pooled CRISPR-Cas9 drop-out screening

Components of the type II CRISPR-Cas complex in bacteria have been used successfully in eukaryotic cells to facilitate rapid and accurate cell line engineering, animal model generation and functional genomic screens. Such developments are providing new opportunities for drug target identification and validation, particularly with the application of pooled genetic screening. As CRISPR-Cas is a relatively new genetic screening tool, it is important to assess its functionality in a number of different cell lines and to analyse potential improvements that might increase the sensitivity of a given screen. To examine critical aspects of screening quality, we constructed ultra-complex libraries containing sgRNA sequences targeting a collection of essential genes. We examined the performance of screening in both haploid and hypotriploid cell lines, using two alternative guide design algorithms and two tracrRNA variants in a time-resolved analysis. Our data indicate that a simple adaptation of the tracrRNA substantially improves the robustness of guide loss during a screen. This modification minimises the requirement for high numbers of sgRNAs targeting each gene, increasing hit scoring and creating a powerful new platform for successful screening

Dot matrix comparison of the <i>C. parapsilosis</i> and <i>C. orthopsilosis</i> genomes.

<p>The horizontal axis represents a joining of the 8 largest <i>C. parapsilosis</i> superscaffolds, sorted by decreasing length. The vertical axis represents a joining of the 8 <i>C. orthopsilosis</i> superscaffolds, sorted and named by decreasing length. Sequence aligning between the two species is represented in black if in the same direction, and in red if in the opposite direction.</p

Horizontal Gene Transfer of a member of the MAT/GAT family in <i>C. orthopsilosis</i>.

<p>(<b>A</b>) Gene order surrounding the MAT/GAT gene in <i>C. orthopsilosis</i>, and the syntenic regions in <i>C. parapsilosis</i> and <i>L. elongisporus</i>. The grey, green and blue arrows represent conserved genes in all three species. The solid red arrow represents an intact ORF in <i>C. orthopsilosis</i>; the transparent red arrow represents a pseudogene in <i>C. parapsilosis</i>. (<b>B</b>) Multiple alignment of the predicted MAT/GAT proteins from <i>Sphingobacterium</i> (Sb1 = ZP_03969495.1, Sb2 = YP_004319944.1), <i>Pedobacter</i> (Pb, YP_003093425.1), <i>C. orthopsilosis</i> (Co) and <i>C. parapsilosis</i> (Cp). Yellow squares mark the presence of frameshifts (forward slash) and internal stop codons (x) that result in a pseudogene in <i>C. parapsilosis</i>.</p

Expansion of a Hyr/Iff gene cluster in <i>C. parapsilosis</i>.

<p>The diagram is redrawn from CGOB, and represents the gene order from 11 genomes of 10 species in the <i>Candida</i> clade. Horizontal blocks of color indicate chromosomes in individual species, and pillars contain orthologs. Adjacent genes are joined by gray lines. The arrows indicate the direction of transcription. Genes 301290–301330 represent a tandem amplification of 5 Hyr/Iff genes that is unique to <i>C. parapsilosis.</i></p