Bounds on the local energy density of holographic CFTs from bulk geometry

The stress tensor is a basic local operator in any field theory; in the context of AdS/CFT, it is the operator which is dual to the bulk geometry itself. Here we exploit this feature by using the bulk geometry to place constraints on the local energy density in static states of holographic $(2+1)$-dimensional CFTs living on a closed (but otherwise generally curved) spatial geometry. We allow for the presence of a marginal scalar deformation, dual to a massless scalar field in the bulk. For certain vacuum states in which the bulk geometry is well-behaved at zero temperature, we find that the bulk equations of motion imply that the local energy density integrated over specific boundary domains is negative. In the absence of scalar deformations, we use the inverse mean curvature flow to show that if the CFT spatial geometry has spherical topology but non-constant curvature, the local energy density must be positive somewhere. This result extends to other topologies, but only for certain types of vacuum; in particular, for a generic toroidal boundary, the vacuum's bulk dual must be the zero-temperature limit of a toroidal black hole.Comment: 14+2 pages, 2 figures. v2: fixed equations (51) and (52

Rich Interfaces for Dependability: Compositional Methods for Dynamic Fault Trees and Arcade models

This paper discusses two behavioural interfaces for reliability analysis: dynamic fault trees, which model the system reliability in terms of the reliability of its components and Arcade, which models the system reliability at an architectural level. For both formalisms, the reliability is analyzed by transforming the DFT or Arcade model to a set of input-output Markov Chains. By using compositional aggregation techniques based on weak bisimilarity, significant reductions in the state space can be obtained

Abstract Interpretation for Probabilistic Termination of Biological Systems

In a previous paper the authors applied the Abstract Interpretation approach for approximating the probabilistic semantics of biological systems, modeled specifically using the Chemical Ground Form calculus. The methodology is based on the idea of representing a set of experiments, which differ only for the initial concentrations, by abstracting the multiplicity of reagents present in a solution, using intervals. In this paper, we refine the approach in order to address probabilistic termination properties. More in details, we introduce a refinement of the abstract LTS semantics and we abstract the probabilistic semantics using a variant of Interval Markov Chains. The abstract probabilistic model safely approximates a set of concrete experiments and reports conservative lower and upper bounds for probabilistic termination

Winner-take-all selection in a neural system with delayed feedback

We consider the effects of temporal delay in a neural feedback system with excitation and inhibition. The topology of our model system reflects the anatomy of the avian isthmic circuitry, a feedback structure found in all classes of vertebrates. We show that the system is capable of performing a `winner-take-all' selection rule for certain combinations of excitatory and inhibitory feedback. In particular, we show that when the time delays are sufficiently large a system with local inhibition and global excitation can function as a `winner-take-all' network and exhibit oscillatory dynamics. We demonstrate how the origin of the oscillations can be attributed to the finite delays through a linear stability analysis.Comment: 8 pages, 6 figure

Model based control strategies for a class of nonlinear mechanical sub-systems

This paper presents a comparison between various control strategies for a class of mechanical actuators common in heavy-duty industry. Typical actuator components are hydraulic or pneumatic elements with static non-linearities, which are commonly referred to as Hammerstein systems. Such static non-linearities may vary in time as a function of the load and hence classical inverse-model based control strategies may deliver sub-optimal performance. This paper investigates the ability of advanced model based control strategies to satisfy a tolerance interval for position error values, overshoot and settling time specifications. Due to the presence of static non-linearity requiring changing direction of movement, control effort is also evaluated in terms of zero crossing frequency (up-down or left-right movement). Simulation and experimental data from a lab setup suggest that sliding mode control is able to improve global performance parameters

Coarse-Grained Model for Phospholipid/Cholesterol Bilayer

We construct a coarse-grained (CG) model for dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers and apply it to large-scale simulation studies of lipid membranes. Our CG model is a two-dimensional representation of the membrane, where the individual lipid and sterol molecules are described by point-like particles. The effective intermolecular interactions used in the model are systematically derived from detailed atomic-scale molecular dynamics simulations using the Inverse Monte Carlo technique, which guarantees that the radial distribution properties of the CG model are consistent with those given by the corresponding atomistic system. We find that the coarse-grained model for the DPPC/cholesterol bilayer is substantially more efficient than atomistic models, providing a speed-up of approximately eight orders of magnitude. The results are in favor of formation of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations, in agreement with the experimental phase diagram of the system. We also explore the limits of the novel coarse-grained model, and discuss the general validity and applicability of the present approach

Introducing monitoring and automation in cartilage tissue engineering, toward controlled clinical translation

The clinical application of tissue engineered products requires to be tightly connected with the possibility to control the process, assess graft quality and define suitable release criteria for implantation. The aim of this work is to establish techniques to standardize and control the in vitro engineering of cartilage grafts. The work is organized in three sub-projects: first a method to predict cell proliferation capacity was studied, then an in line technique to monitor the draft during in vitro culture was developed and, finally, a culture system for the reproducible production of engineered cartilage was designed and validated. Real-time measurements of human chondrocyte heat production during in vitro proliferation. Isothermal microcalorimetry (IMC) is an on-line, non-destructive and high resolution technique. In this project we aimed to verify the possibility to apply IMC to monitor the metabolic activity of primary human articular chondrocytes (HAC) during their in vitro proliferation. Indeed, currently, many clinically available cell therapy products for the repair of cartilage lesions involve a process of in vitro cell expansion. Establishing a model system able to predict the efficiency of this lengthy, labor-intensive, and challenging to standardize step could have a great potential impact on the manufacturing process. In this study an optimized experimental set up was first established, to reproducible acquire heat flow data; then it was demonstrated that the HAC proliferation within the IMC-based model was similar to proliferation under standard culture conditions, verifying its relevance for simulating the typical cell culture application. Finally, based on the results from 12 independent donors, the possible predictive potential of this technique was assessed. Online monitoring of oxygen as a non-destructive method to quantify cells in engineered 3D tissue constructs. This project aimed at assessing a technique to monitor graft quality during production and/or at release. A quantitative method to monitor the cells number in a 3D construct, based on the on-line measurement of the oxygen consumption in a perfusion based bioreactor system was developed. Oxygen levels dissolved in the medium were monitored on line, by two chemo-optic flow-through micro-oxygen sensors connected at the inlet and the outlet of the bioreactor scaffold chamber. A destructive DNA assay served to quantify the number of cells at the end of the culture. Thus the oxygen consumption per cell could be calculated as the oxygen drop across the perfused constructs at the end of the culture period and the number of cells quantified by DNA. The method developed would allow to non-invasively monitoring in real time the number of chondrocytes on the scaffold. Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing. The aim of this project was to upscale the size of engineered human cartilage grafts. The main aim of this project consisted in the design and prototyping of a direct perfusion bioreactor system, based on fluidodynamic models (realized in collaboration with the Institute for Bioengineering of Catalonia, Spain), able to guarantee homogeneous seeding and culture conditions trough the entire scaffold surface. The system was then validated and the capability to reproducibly support the process of tissue development was tested by histological, biochemical and biomechanical assays. Within the same project the automation of the designed scaled up bioreactor system, thought as a stand alone system, was proposed. A prototype was realized in collaboration with Applikon Biotechnology BV, The Netherlands. The developed system allows to achieve within a closed environment both cell seeding and culture, controlling some important environmental parameters (e.g. temperature, CO2 and O2 tension), coordinating the medium flow and tracking culture development. The system represents a relevant step toward process automation in tissue engineering and, as previously discussed, enhancing the automation level is an important requirement in order to move towards standardized protocols of graft generation for the clinical practice. These techniques will be critical towards a controlled and standardized procedure for clinical implementation of tissue engineering products and will provide the basis for controlled in vitro studies on cartilage development. Indeed the resulting methods have already been integrated in a streamlined, controlled, bioreactor based protocol for the in vitro production of up scaled engineered cartilage drafts. Moreover the techniques described will serve as the foundation for a recently approved Collaborative Project funded by the European Union, having the goal to produce cartilage tissue grafts. In order to reach this goal the research based technologies and processes described in this dissertation will be adapted for GMP compliance and conformance to regulatory guidelines for the production of engineered tissues for clinical use, which will be tested in a clinical trial

A Bound on Holographic Entanglement Entropy from Inverse Mean Curvature Flow

Entanglement entropies are notoriously difficult to compute. Large-N strongly-coupled holographic CFTs are an important exception, where the AdS/CFT dictionary gives the entanglement entropy of a CFT region in terms of the area of an extremal bulk surface anchored to the AdS boundary. Using this prescription, we show -- for quite general states of (2+1)-dimensional such CFTs -- that the renormalized entanglement entropy of any region of the CFT is bounded from above by a weighted local energy density. The key ingredient in this construction is the inverse mean curvature (IMC) flow, which we suitably generalize to flows of surfaces anchored to the AdS boundary. Our bound can then be thought of as a "subregion" Penrose inequality in asymptotically locally AdS spacetimes, similar to the Penrose inequalities obtained from IMC flows in asymptotically flat spacetimes. Combining the result with positivity of relative entropy, we argue that our bound is valid perturbatively in 1/N, and conjecture that a restricted version of it holds in any CFT.Comment: 33+7 pages, 7 figures. v2: addressed referee comment

Beyond Counting: New Perspectives on the Active IPv4 Address Space

In this study, we report on techniques and analyses that enable us to capture Internet-wide activity at individual IP address-level granularity by relying on server logs of a large commercial content delivery network (CDN) that serves close to 3 trillion HTTP requests on a daily basis. Across the whole of 2015, these logs recorded client activity involving 1.2 billion unique IPv4 addresses, the highest ever measured, in agreement with recent estimates. Monthly client IPv4 address counts showed constant growth for years prior, but since 2014, the IPv4 count has stagnated while IPv6 counts have grown. Thus, it seems we have entered an era marked by increased complexity, one in which the sole enumeration of active IPv4 addresses is of little use to characterize recent growth of the Internet as a whole. With this observation in mind, we consider new points of view in the study of global IPv4 address activity. Our analysis shows significant churn in active IPv4 addresses: the set of active IPv4 addresses varies by as much as 25% over the course of a year. Second, by looking across the active addresses in a prefix, we are able to identify and attribute activity patterns to network restructurings, user behaviors, and, in particular, various address assignment practices. Third, by combining spatio-temporal measures of address utilization with measures of traffic volume, and sampling-based estimates of relative host counts, we present novel perspectives on worldwide IPv4 address activity, including empirical observation of under-utilization in some areas, and complete utilization, or exhaustion, in others.Comment: in Proceedings of ACM IMC 201