The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions

As the global health burden of chronic disease increases, end-stage organ failure has become a costly and intractable problem. De novo organ creation is one of the long-term goals of the medical community. One of the promising avenues is that of tissue engineering: the use of biomaterials to create cells, structures, or even whole organs. Tissue engineering has emerged from its nascent stage, with several proof-of-principle trials performed across various tissue types. As tissue engineering moves from the realm of case trials to broader clinical study, three major questions have emerged: (1) Can the production of biological scaffolds be scaled up accordingly to meet current and future demands without generating an unfavorable immune response? (2) Are biological scaffolds plus or minus the inclusion of cells replaced by scar tissue or native functional tissue? (3) Can tissue-engineered organs be grown in children and adolescents given the different immune profiles of children? In this review, we highlight current research in the immunological response to tissue-engineered biomaterials, cells, and whole organs and address the answers to these questions

A weighted reduced basis method for parabolic PDEs with random data

This work considers a weighted POD-greedy method to estimate statistical outputs parabolic PDE problems with parametrized random data. The key idea of weighted reduced basis methods is to weight the parameter-dependent error estimate according to a probability measure in the set-up of the reduced space. The error of stochastic finite element solutions is usually measured in a root mean square sense regarding their dependence on the stochastic input parameters. An orthogonal projection of a snapshot set onto a corresponding POD basis defines an optimum reduced approximation in terms of a Monte Carlo discretization of the root mean square error. The errors of a weighted POD-greedy Galerkin solution are compared against an orthogonal projection of the underlying snapshots onto a POD basis for a numerical example involving thermal conduction. In particular, it is assessed whether a weighted POD-greedy solutions is able to come significantly closer to the optimum than a non-weighted equivalent. Additionally, the performance of a weighted POD-greedy Galerkin solution is considered with respect to the mean absolute error of an adjoint-corrected functional of the reduced solution.Comment: 15 pages, 4 figure

Effective field approach to the Ising film in a transverse field

We study the phase transitions of the spin-1/2 Ising film in a transverse field within the framework of the effective field theory. We evaluate the critical temperature of the film as a function of the exchange interactions, the transverse field and the film thickness. We find that, if the ratio of the surface exchange interactions to the bulk ones R=Js/J is smaller than a critical value Rc, the critical temperature Tc/J of the film is smaller than the bulk critical temperature Tc^B/J and approaches Tc^B/J as R increases further. On the other hand, if R>Rc, Tc/J is larger than both the bulk Tc^B/J and the surface Tc^S/J critical temperatures of the corresponding semi-infinite system, and approaches Tc^S as R increases further.Comment: 16 pages, 5 figures, elsart.cls (included

Investigating users’ perspectives on the development of bike-sharing in Shanghai

High levels of car dependence have caused tremendous challenges for sustainable transport development. Transport planners, therefore, seek ways of replacing motor vehicles, as well as increasing the proportion of active travel. The bike-sharing scheme can be seen as an effective way of doing so, particularly in Asian cities. The aim of this paper is to investigate users’ perspectives on the development of bike-sharing using Shanghai as an example. Semi-structured interviews are used to examine the main factors motivating and impeding the development of the bike-sharing scheme in Shanghai. Our findings show that convenience, saving time and financial savings are the major motivations; whereas problems with bicycles being poorly maintained and abused by users, operational issues, financial issues and an unsuitable business model are the major obstacles. In addition, the findings also suggest that a public and private partnership could be the best option for running a sustainable bike-sharing scheme with clear areas of responsibility. Financial incentives, a bicycle-friendly infrastructure, regular operational management and supportive policies should be prioritised. In order to achieve the targets set by the Shanghai Master Plan 2035, transport planners and policymakers should integrate the bike-sharing scheme within the wider active travel system

Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Finding Your Mate at a Cocktail Party: Frequency Separation Promotes Auditory Stream Segregation of Concurrent Voices in Multi-Species Frog Choruses

Vocal communication in crowded social environments is a difficult problem for both humans and nonhuman animals. Yet many important social behaviors require listeners to detect, recognize, and discriminate among signals in a complex acoustic milieu comprising the overlapping signals of multiple individuals, often of multiple species. Humans exploit a relatively small number of acoustic cues to segregate overlapping voices (as well as other mixtures of concurrent sounds, like polyphonic music). By comparison, we know little about how nonhuman animals are adapted to solve similar communication problems. One important cue enabling source segregation in human speech communication is that of frequency separation between concurrent voices: differences in frequency promote perceptual segregation of overlapping voices into separate “auditory streams” that can be followed through time. In this study, we show that frequency separation (ΔF) also enables frogs to segregate concurrent vocalizations, such as those routinely encountered in mixed-species breeding choruses. We presented female gray treefrogs (Hyla chrysoscelis) with a pulsed target signal (simulating an attractive conspecific call) in the presence of a continuous stream of distractor pulses (simulating an overlapping, unattractive heterospecific call). When the ΔF between target and distractor was small (e.g., ≤3 semitones), females exhibited low levels of responsiveness, indicating a failure to recognize the target as an attractive signal when the distractor had a similar frequency. Subjects became increasingly more responsive to the target, as indicated by shorter latencies for phonotaxis, as the ΔF between target and distractor increased (e.g., ΔF = 6–12 semitones). These results support the conclusion that gray treefrogs, like humans, can exploit frequency separation as a perceptual cue to segregate concurrent voices in noisy social environments. The ability of these frogs to segregate concurrent voices based on frequency separation may involve ancient hearing mechanisms for source segregation shared with humans and other vertebrates