Intertwining Relations for the Deformed D1D5 CFT

The Higgs branch of the D1D5 system flows in the infrared to a two-dimensional N=(4,4) SCFT. This system is believed to have an "orbifold point" in its moduli space where the SCFT is a free sigma model with target space the symmetric product of copies of four-tori; however, at the orbifold point gravity is strongly coupled and to reach the supergravity point one needs to turn on the four exactly marginal deformations corresponding to the blow-up modes of the orbifold SCFT. Recently, technology has been developed for studying these deformations and perturbing the D1D5 CFT off its orbifold point. We present a new method for computing the general effect of a single application of the deformation operators. The method takes the form of intertwining relations that map operators in the untwisted sector before application of the deformation operator to operators in the 2-twisted sector after the application of the deformation operator. This method is computationally more direct, and may be of theoretical interest. This line of inquiry should ultimately have relevance for black hole physics.Comment: latex, 23 pages, 3 figure

New instability of non-extremal black holes: spitting out supertubes

We search for stable bound states of non-extremal rotating three-charge black holes in five dimensions (Cvetic-Youm black holes) and supertubes. We do this by studying the potential of supertube probes in the non-extremal black hole background and find that generically the marginally bound state of the supersymmetric limit becomes metastable and disappears with non-extremality (higher temperature). However near extremality there is a range of parameters allowing for stable bound states, which have lower energy than the supertube-black hole merger. Angular momentum is crucial for this effect. We use this setup in the D1-D5 decoupling limit to map a thermodynamic instability of the CFT (a new phase which is entropically dominant over the black hole phase) to a tunneling instability of the black hole towards the supertube-black hole bound state. This generalizes the results of ArXiv:1108.0411 [hep-th], which mapped an entropy enigma in the bulk to the dual CFT in a supersymmetric setup.Comment: 28 pages + appendix, 15 figures, v2: References added, typos corrected. Version published in JHE

CamOptimus: a tool for exploiting complex adaptive evolution to optimize experiments and processes in biotechnology

Multiple interacting factors affect the performance of engineered biological systems in synthetic biology projects. The complexity of these biological systems means that experimental design should often be treated as a multiparametric optimization problem. However, the available methodologies are either impractical, due to a combinatorial explosion in the number of experiments to be performed, or are inaccessible to most experimentalists due to the lack of publicly available, user-friendly software. Although evolutionary algorithms may be employed as alternative approaches to optimize experimental design, the lack of simple-to-use software again restricts their use to specialist practitioners. In addition, the lack of subsidiary approaches to further investigate critical factors and their interactions prevents the full analysis and exploitation of the biotechnological system. We have addressed these problems and, here, provide a simple-to-use and freely available graphical user interface to empower a broad range of experimental biologists to employ complex evolutionary algorithms to optimize their experimental designs. Our approach exploits a Genetic Algorithm to discover the subspace containing the optimal combination of parameters, and Symbolic Regression to construct a model to evaluate the sensitivity of the experiment to each parameter under investigation. We demonstrate the utility of this method using an example in which the culture conditions for the microbial production of a bioactive human protein are optimized. CamOptimus is available through: (https://doi.org/10.17863/CAM.10257).EU 7th Framework Programme (BIOLEDGE Contract No: 289126 to S. G. O and J. R), BBSRC (BRIC2.2 to S. G. O. and N. K. H. S.), Synthetic Biology Research Initiative Cambridge (SynBioFund to D. D., A. C. C. and J. M. L. D.

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Excitations in the deformed D1D5 CFT

We perform some simple computations for the first order deformation of the D1D5 CFT off its orbifold point. It had been shown earlier that under this deformation the vacuum state changes to a squeezed state (with the further action of a supercharge). We now start with states containing one or two initial quanta and write down the corresponding states obtained under the action of deformation operator. The result is relevant to the evolution of an initial excitation in the CFT dual to the near extremal D1D5 black hole: when a left and a right moving excitation collide in the CFT, the deformation operator spreads their energy over a larger number of quanta, thus evolving the state towards the infrared.Comment: 26 pages, Latex, 4 figure

Deforming the D1D5 CFT away from the orbifold point

The D1D5 brane bound state is believed to have an `orbifold point' in its moduli space which is the analogue of the free Yang Mills theory for the D3 brane bound state. The supergravity geometry generated by D1 and D5 branes is described by a different point in moduli space, and in moving towards this point we have to deform the CFT by a marginal operator: the `twist' which links together two copies of the CFT. In this paper we find the effect of this deformation operator on the simplest physical state of the CFT -- the Ramond vacuum. The twist deformation leads to a final state that is populated by pairs of excitations like those in a squeezed state. We find the coefficients characterizing the distribution of these particle pairs (for both bosons and fermions) and thus write this final state in closed form.Comment: 30 pages, 4 figures, Late