Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq

The utilisation of genome-wide transcriptomics has played a pivotal role in advancing the field of toxicology, allowing the mapping of transcriptional signatures to chemical exposures. These activities have uncovered several transcriptionally regulated pathways that can be utilised for assessing the perturbation impact of a chemical and also the identification of toxic mode of action. However, current transcriptomic platforms are not very amenable to high-throughput workflows due to, high cost, complexities in sample preparation and relatively complex bioinformatic analysis. Thus, transcriptomic investigations are usually limited in dose and time dimensions and are, therefore, not optimal for implementation in risk assessment workflows. In this study, we investigated a new cost-effective, transcriptomic assay, TempO-Seq, which alleviates the aforementioned limitations. This technique was evaluated in a 6-compound screen, utilising differentiated kidney (RPTEC/TERT1) and liver (HepaRG) cells and compared to non-transcriptomic label-free sensitive endpoints of chemical-induced disturbances, namely phase contrast morphology, xCELLigence and glycolysis. Non-proliferating cell monolayers were exposed to six sub-lethal concentrations of each compound for 24 h. The results show that utilising a 2839 gene panel, it is possible to discriminate basal tissue-specific signatures, generate dose-response relationships and to discriminate compound-specific and cell type-specific responses. This study also reiterates previous findings that chemical-induced transcriptomic alterations occur prior to cytotoxicity and that transcriptomics provides in depth mechanistic information of the effects of chemicals on cellular transcriptional responses. TempO-Seq is a robust transcriptomic platform that is well suited for in vitro toxicity experiments.Horizon 2020(H2020)68100

Coarse-Graining the Lin-Maldacena Geometries

The Lin-Maldacena geometries are nonsingular gravity duals to degenerate vacuum states of a family of field theories with SU(2|4) supersymmetry. In this note, we show that at large N, where the number of vacuum states is large, there is a natural `macroscopic' description of typical states, giving rise to a set of coarse-grained geometries. For a given coarse-grained state, we can associate an entropy related to the number of underlying microstates. We find a simple formula for this entropy in terms of the data that specify the geometry. We see that this entropy function is zero for the original microstate geometries and maximized for a certain ``typical state'' geometry, which we argue is the gravity dual to the zero-temperature limit of the thermal state of the corresponding field theory. Finally, we note that the coarse-grained geometries are singular if and only if the entropy function is non-zero.Comment: 29 pages, LaTeX, 3 figures; v2 references adde

From Gravitons to Giants

We discuss exact quantization of gravitational fluctuations in the half-BPS sector around AdS$_5 \times$S$^5$ background, using the dual super Yang-Mills theory. For this purpose we employ the recently developed techniques for exact bosonization of a finite number $N$ of fermions in terms of $N$ bosonic oscillators. An exact computation of the three-point correlation function of gravitons for finite $N$ shows that they become strongly coupled at sufficiently high energies, with an interaction that grows exponentially in $N$. We show that even at such high energies a description of the bulk physics in terms of weakly interacting particles can be constructed. The single particle states providing such a description are created by our bosonic oscillators or equivalently these are the multi-graviton states corresponding to the so-called Schur polynomials. Both represent single giant graviton states in the bulk. Multi-particle states corresponding to multi-giant gravitons are, however, different, since interactions among our bosons vanish identically, while the Schur polynomials are weakly interacting at high enough energies.Comment: v2-references added, minor changes and typos corrected; 24 pages, latex, 3 epsf figure

The Oedipal Paradigm in Group Development

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68383/2/10.1177_104649647300400302.pd

A Monte-Carlo study of the AdS/CFT correspondence: an exploration of quantum gravity effects

In this paper we study the AdS/CFT correspondence for N=4 SYM with gauge group U(N), compactified on S^3 in four dimensions using Monte-Carlo techniques. The simulation is based on a particular reduction of degrees of freedom to commuting matrices of constant fields, and in particular, we can write the wave functions of these degrees of freedom exactly. The square of the wave function is equivalent to a probability density for a Boltzman gas of interacting particles in six dimensions. From the simulation we can extract the density particle distribution for each wave function, and this distribution can be interpreted as a special geometric locus in the gravitational dual. Studying the wave functions associated to half-BPS giant gravitons, we are able to show that the matrix model can measure the Planck scale directly. We also show that the output of our simulation seems to match various theoretical expectations in the large N limit and that it captures 1/N effects as statistical fluctuations of the Boltzman gas with the expected scaling. Our results suggest that this is a very promising approach to explore quantum corrections and effects in gravitational physics on AdS spaces.Comment: 40 pages, 7 figures, uses JHEP. v2: references adde

Extended Fermion Representation of Multi-Charge 1/2-BPS Operators in AdS/CFT -- Towards Field Theory of D-Branes --

We extend the fermion representation of single-charge 1/2-BPS operators in the four-dimensional N=4 super Yang-Mills theory to general (multi-charge) 1/2-BPS operators such that all six directions of scalar fields play roles on an equal footing. This enables us to construct a field-theorectic representation for a second-quantized system of spherical D3-branes in the 1/2-BPS sector. The Fock space of D3-branes is characterized by a novel exclusion principle (called `Dexclusion' principle), and also by a nonlocality which is consistent with the spacetime uncertainty relation. The Dexclusion principle is realized by composites of two operators, obeying the usual canonical anticommutation relation and the Cuntz algebra, respectively. The nonlocality appears as a consequence of a superselction rule associated with a symmetry which is related to the scale invariance of the super Yang-Mills theory. The entropy of the so-called superstars, with multiple charges, which have been proposed to be geometries corresponding to the condensation of giant gravitons is discussed from our viewpoint and is argued to be consistent with the Dexclusion principle. Our construction may be regarded as a first step towards a possible new framework of general D-brane field theory.Comment: 43 pages, 4 figures; version 2, corrected typos and added reference

Entropy of near-extremal black holes in AdS_5

We construct the microstates of near-extremal black holes in AdS_5 x S^5 as gases of defects distributed in heavy BPS operators in the dual SU(N) Yang-Mills theory. These defects describe open strings on spherical D3-branes in the S^5, and we show that they dominate the entropy by directly enumerating them and comparing the results with a partition sum calculation. We display new decoupling limits in which the field theory of the lightest open strings on the D-branes becomes dual to a near-horizon region of the black hole geometry. In the single-charge black hole we find evidence for an infrared duality between SU(N) Yang-Mills theories that exchanges the rank of the gauge group with an R-charge. In the two-charge case (where pairs of branes intersect on a line), the decoupled geometry includes an AdS_3 factor with a two-dimensional CFT dual. The degeneracy in this CFT accounts for the black hole entropy. In the three-charge case (where triples of branes intersect at a point), the decoupled geometry contains an AdS_2 factor. Below a certain critical mass, the two-charge system displays solutions with naked timelike singularities even though they do not violate a BPS bound. We suggest a string theoretic resolution of these singularities.Comment: LaTeX; v2: references and a few additional comments adde

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo