Enzymatic Cross-Linking of Dynamic Thiol-Norbornene Click Hydrogels

Enzyme-mediated in situ forming hydrogels are attractive for many biomedical applications because gelation afforded by enzymatic reactions can be readily controlled not only by tuning macromer compositions, but also by adjusting enzyme kinetics. For example, horseradish peroxidase (HRP) has been used extensively for in situ cross-linking of macromers containing hydroxyl-phenol groups. The use of HRP to initiate thiol-allylether polymerization has also been reported, yet no prior study has demonstrated enzymatic initiation of thiol-norbornene gelation. In this study, we discovered that HRP can generate the thiyl radicals needed for initiating thiol-norbornene hydrogelation, which has only been demonstrated previously using photopolymerization. Enzymatic thiol-norbornene gelation not only overcomes light attenuation issue commonly observed in photopolymerized hydrogels, but also preserves modularity of the cross-linking. In particular, we prepared modular hydrogels from two sets of norbornene-modified macromers, 8-arm poly(ethylene glycol)-norbornene (PEG8NB) and gelatin-norbornene (GelNB). Bis-cysteine-containing peptides or PEG-tetra-thiol (PEG4SH) was used as a cross-linker for forming enzymatically and orthogonally polymerized hydrogel. For HRP-initiated PEG-peptide hydrogel cross-linking, gelation efficiency was significantly improved via adding tyrosine residues on the peptide cross-linkers. Interestingly, these additional tyrosine residues did not form permanent dityrosine cross-links following HRP-induced gelation. As a result, they remained available for tyrosinase-mediated secondary cross-linking, which dynamically increased hydrogel stiffness. In addition to material characterizations, we also found that both PEG- and gelatin-based hydrogels exhibited excellent cytocompatibility for dynamic 3D cell culture. The enzymatic thiol-norbornene gelation scheme presented here offers a new cross-linking mechanism for preparing modularly and dynamically cross-linked hydrogels

Parallel Toolkit for Measuring the Quality of Network Community Structure

Many networks display community structure which identifies groups of nodes within which connections are denser than between them. Detecting and characterizing such community structure, which is known as community detection, is one of the fundamental issues in the study of network systems. It has received a considerable attention in the last years. Numerous techniques have been developed for both efficient and effective community detection. Among them, the most efficient algorithm is the label propagation algorithm whose computational complexity is O(|E|). Although it is linear in the number of edges, the running time is still too long for very large networks, creating the need for parallel community detection. Also, computing community quality metrics for community structure is computationally expensive both with and without ground truth. However, to date we are not aware of any effort to introduce parallelism for this problem. In this paper, we provide a parallel toolkit to calculate the values of such metrics. We evaluate the parallel algorithms on both distributed memory machine and shared memory machine. The experimental results show that they yield a significant performance gain over sequential execution in terms of total running time, speedup, and efficiency.Comment: 8 pages; in Network Intelligence Conference (ENIC), 2014 Europea

Self-directedness, integration and higher cognition

In this paper I discuss connections between self-directedness, integration and higher cognition. I present a model of self-directedness as a basis for approaching higher cognition from a situated cognition perspective. According to this model increases in sensorimotor complexity create pressure for integrative higher order control and learning processes for acquiring information about the context in which action occurs. This generates complex articulated abstractive information processing, which forms the major basis for higher cognition. I present evidence that indicates that the same integrative characteristics found in lower cognitive process such as motor adaptation are present in a range of higher cognitive process, including conceptual learning. This account helps explain situated cognition phenomena in humans because the integrative processes by which the brain adapts to control interaction are relatively agnostic concerning the source of the structure participating in the process. Thus, from the perspective of the motor control system using a tool is not fundamentally different to simply controlling an arm

Semantic transfer in Verbmobil

This paper is a detailed discussion of semantic transfer in the context of the Verbmobil Machine Translation project. The use of semantic transfer as a translation mechanism is introduced and justified by comparison with alternative approaches. Some criteria for evaluation of transfer frameworks are discussed and a comparison is made of three different approaches to the representation of translation rules or equivalences. This is followed by a discussion of control of application of transfer rules and interaction with a domain description and inference component