Endogenous musculoskeletal tissue engineering - a focused perspective

Two major difficulties facing widespread clinical implementation of existing Tissue Engineering (TE) strategies for the treatment of musculoskeletal disorders are (1) the cost, space and time required for ex vivo culture of a patient’s autologous cells prior to re-implantation as part of a TE construct, and (2) the potential risks and availability constraints associated with transplanting exogenous (foreign) cells. These hurdles have led to recent interest in endogenous TE strategies, in which the regenerative potential of a patient’s own cells is harnessed to promote tissue regrowth without ex vivo cell culture. This article provides a focused perspective on key issues in the development of endogenous TE strategies, progress to date, and suggested future research directions toward endogenous repair and regeneration of musculoskeletal tissues and organs

Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear

An early and crucial event in vertebrate inner ear development is the acquisition of axial identities that in turn dictate the positions of all subsequent inner ear components. Here, we focus on the role of the hindbrain in establishment of inner ear axes and show that axial specification occurs well after otic placode formation in chicken. Anteroposterior (AP) rotation of the hindbrain prior to specification of this axis does not affect the normal AP orientation and morphogenesis of the inner ear. By contrast, reversing the dorsoventral (DV) axis of the hindbrain results in changing the DV axial identity of the inner ear. Expression patterns of several ventrally expressed otic genes such as NeuroD, Lunatic fringe (Lfng) and Six1 are shifted dorsally, whereas the expression pattern of a normally dorsal-specific gene, Gbx2, is abolished. Removing the source of Sonic Hedgehog (SHH) by ablating the floor plate and/or notochord, or inhibiting SHH function using an antibody that blocks SHH bioactivity results in loss of ventral inner ear structures. Our results indicate that SHH, together with other signals from the hindbrain, are important for patterning the ventral axis of the inner ear. Taken together, our studies suggest that tissue(s) other than the hindbrain confer AP axial information whereas signals from the hindbrain are necessary and sufficient for the DV axial patterning of the inner ear

Language Interaction and Quality Issues: An Exploratory Study

Most software systems are complex and often composed of a large number of artifacts. To realize each different artifacts specific techniques are used resorting on different abstractions, languages and tools. Successful composition of different elements requires coherence among them. Unfortunately constraints between artifacts written in different languages are usually not formally expressed neither checked by supporting tools; as consequence they can be a source of problems. In this paper we explore the role of the relations between artifacts written in different languages by means of a case study on the Hadoop open source project. We present the problem introducing the related terminology, we quantify the phenomenon and investigate the relation with defect pronenes

The Strict Liability in Fault and the Fault in Strict Liability

Tort scholars have long been obsessed with the dichotomy between strict liability and liability based on fault or wrongdoing. We argue that this is a false dichotomy. Torts such as battery, libel, negligence, and nuisance are wrongs, yet all are “strictly” defined in the sense of setting objective and thus quite demanding standards of conduct. We explain this basic insight under the heading of “the strict liability in fault.” We then turn to the special case of liability for abnormally dangerous activities, which at times really does involve liability without wrongdoing. Through an examination of this odd corner of tort law, we isolate “the fault in strict liability”—that is, the fault line between the wrongs-based form of strict liability that is frequently an aspect of tort liability and the wrongs-free form of strict liability that is found only within the very narrow domain of liability for abnormally dangerous activities. We conclude by defending these two features of the common law of tort: the strictness of the terms on which it defines wrongdoing and its begrudging willingness to recognize, in one special kind of case, liability without wrongdoing

A-posteriori analysis and adaptive algorithms for the quasicontinuum method in one dimension

The quasicontinuum (QC) method is a coarse-graining technique for reducing the complexity of atomistic simulations in a static and quasistatic setting. In this paper we give an a-posteriori error analysis for the quasi-continuum method in one dimension. We consider atomistic models with Lennard-Jones type finite-range interactions.\ud \ud We prove that, for a stable QC solution with a sufficiently small residual, which is computed in a discrete Sobolev-type norm, there exists an exact solution of the atomistic model problem for which an a-posteriori error estimate holds. We then derive practically computable bounds on the residual and on the inf-sup constants which measure the stability of the QC solution.\ud \ud Finally, we supplement the QC method with a proximal point optimization method with local-error control. We prove that the parameters can be adjusted so that at each step of the optimization algorithm there exists an exact solution to a related atomistic problem whose distance to the numerical solution is smaller than a pre-set tolerance.\ud \ud Key words and phrases: atomistic material models, quasicontinuum method, error analysis, adaptivity, stability\ud \ud The first author acknowledges the financial support received from the European research project HPRB-CT-2002-00284: New Materials, Adaptive Systems and their Nonlinearities. Modelling, Control and Numerical Simulation, and the kind hospitality of Carlo Lovadina and Matteo Negri (University of Pavia).\ud \ud We would like to thank Nick Gould for his advice on practical optimization methods, particularly on proximal point algorithms