Cluster Dynamics for Randomly Frustrated Systems with Finite Connectivity

In simulations of some infinite range spin glass systems with finite connectivity, it is found that for any resonable computational time, the saturatedenergy per spin that is achieved by a cluster algorithm is lowered in comparison to that achieved by Metropolis dynamics.The gap between the average energies obtained from these two dynamics is robust with respect to variations of the annealing schedule. For some probability distribution of the interactions the ground state energy is calculated analytically within the replica symmetry assumptionand is found to be saturated by a cluster algorithm.Comment: Revtex, 4 pages with 3 figure

Empirical validation of a rat in vitro organ slice model as a tool for in vivo clearance prediction

Tissue slices have been shown to be a valuable tool to predict metabolism of novel drugs. However, besides the numerous advantages of their use for this purpose, some potential drawbacks also exist, including reported poor penetration of drugs into the inner cell layers of slices and loss of metabolic capacity during prolonged incubation, leading to underprediction of metabolic clearance. In the present study, we empirically identified ( and quantified) sources of underprediction using rat tissue slices of lung, intestine, kidney, and liver and found that thin liver slices ( +/- 100 mu m) metabolized model substrates ( 7- hydroxycoumarin, testosterone, warfarin, 7- ethoxycoumarin, midazolam, haloperidol, and quinidine) as rapidly as isolated hepatocytes. Furthermore, it was found that organ slices remain metabolically active for sufficient periods of incubation, enabling study of the kinetics of low clearance compounds. In addition, we determined the influence of albumin on the clearance prediction of six model substrates. For three of these substrates, the intrinsic clearance in the presence of albumin was approximately 3 times higher than that obtained from incubations without albumin, but corrected for unbound fraction. This resulted in a much more accurate prediction of in vivo whole body metabolic clearance for these compounds. Collectively, these results show that drawbacks of the use of slices for clearance prediction are largely surmountable. Provided that thin liver slices and physiological albumin concentration are used, whole body metabolic clearance is predicted with acceptable ( 2- fold) accuracy with organ slices. These results emphasize the applicability of organ slices in this field of research

How Smart are Smart Materials?:A Conceptual and Ethical Analysis of Smart Lifelike Materials for the Design of Regenerative Valve Implants

It may soon become possible not just to replace, but to re-grow healthy tissues after injury or disease, because of innovations in the field of Regenerative Medicine. One particularly promising innovation is a regenerative valve implant to treat people with heart valve disease. These implants are fabricated from so-called 'smart', 'lifelike' materials. Implanted inside a heart, these implants stimulate re-growth of a healthy, living heart valve. While the technological development advances, the ethical implications of this new technology are still unclear and a clear conceptual understanding of the notions 'smart' and 'lifelike' is currently lacking. In this paper, we explore the conceptual and ethical implications of the development of smart lifelike materials for the design of regenerative implants, by analysing heart valve implants as a showcase. In our conceptual analysis, we show that the materials are considered 'smart' because they can communicate with human tissues, and 'lifelike' because they are structurally similar to these tissues. This shows that regenerative valve implants become intimately integrated in the living tissues of the human body. As such, they manifest the ontological entanglement of body and technology. In our ethical analysis, we argue this is ethically significant in at least two ways: It exacerbates the irreversibility of the implantation procedure, and it might affect the embodied experience of the implant recipient. With our conceptual and ethical analysis, we aim to contribute to responsible development of smart lifelike materials and regenerative implants.</p

A value hierarchy for inclusive design of heart valve implants in regenerative medicine

Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase. Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants. Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need. Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need.</p

Statistical mechanics of the random K-SAT model

The Random K-Satisfiability Problem, consisting in verifying the existence of an assignment of N Boolean variables that satisfy a set of M=alpha N random logical clauses containing K variables each, is studied using the replica symmetric framework of diluted disordered systems. We present an exact iterative scheme for the replica symmetric functional order parameter together for the different cases of interest K=2, K>= 3 and K>>1. The calculation of the number of solutions, which allowed us [Phys. Rev. Lett. 76, 3881 (1996)] to predict a first order jump at the threshold where the Boolean expressions become unsatisfiable with probability one, is thoroughly displayed. In the case K=2, the (rigorously known) critical value (alpha=1) of the number of clauses per Boolean variable is recovered while for K>=3 we show that the system exhibits a replica symmetry breaking transition. The annealed approximation is proven to be exact for large K.Comment: 34 pages + 1 table + 8 fig., submitted to Phys. Rev. E, new section added and references update

A value hierarchy for inclusive design of heart valve implants in regenerative medicine

Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase. Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants. Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need. Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need.</p

Typical Performance of Gallager-type Error-Correcting Codes

The performance of Gallager's error-correcting code is investigated via methods of statistical physics. In this approach, the transmitted codeword comprises products of the original message bits selected by two randomly-constructed sparse matrices; the number of non-zero row/column elements in these matrices constitutes a family of codes. We show that Shannon's channel capacity is saturated for many of the codes while slightly lower performance is obtained for others which may be of higher practical relevance. Decoding aspects are considered by employing the TAP approach which is identical to the commonly used belief-propagation-based decoding.Comment: 6 pages, latex, 1 figur

Exact solutions for diluted spin glasses and optimization problems

We study the low temperature properties of p-spin glass models with finite connectivity and of some optimization problems. Using a one-step functional replica symmetry breaking Ansatz we can solve exactly the saddle-point equations for graphs with uniform connectivity. The resulting ground state energy is in perfect agreement with numerical simulations. For fluctuating connectivity graphs, the same Ansatz can be used in a variational way: For p-spin models (known as p-XOR-SAT in computer science) it provides the exact configurational entropy together with the dynamical and static critical connectivities (for p=3, \gamma_d=0.818 and \gamma_s=0.918 resp.), whereas for hard optimization problems like 3-SAT or Bicoloring it provides new upper bounds for their critical thresholds (\gamma_c^{var}=4.396 and \gamma_c^{var}=2.149 resp.).Comment: 4 pages, 1 figure, accepted for publication in PR

Metastable configurations of spin models on random graphs

One-flip stable configurations of an Ising-model on a random graph with fluctuating connectivity are examined. In order to perform the quenched average of the number of stable configurations we introduce a global order-parameter function with two arguments. The analytical results are compared with numerical simulations.Comment: 11 pages Revtex, minor changes, to appear in Phys. Rev.