Treatment of unawareness of memory deficits in adults with brain injury: Three case studies.

Examined the use of an intervention for reducing unawareness of memory deficits in 3 male adults (aged 20–25 yrs) with brain injury. High predicted test scores on a brief multiparametric memory test, relative to actual test scores, were considered underestimations of symptom severity (unawareness). An estimation technique, feedback, and explicit positive reinforcement for decreases in discrepancies between predicted and actual scores were used to reduce unawareness. Differences between Ss' predicted and actual scores decreased over time following treatment for all Ss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins.     

Axiomatizing the Logical Core of XPath 2.0

The first aim of this paper is to present the logical core of XPath 2.0: a logically clean, decidable fragment, which includes most navigational features of XPath 2.0 (complex counting conditions and data joins are not supported, as they lead to undecidability). The second aim is to provide a list of equations completely axiomatizing query equivalence in this language (i.e., all other query equivalences can be derived from these). A preliminary version of this paper was published in the proceedings of ICDT 2007. We would like to thank Jan Hidders for pointing us to the interesting question of stronger forms of completeness (cf. Sect. 4.3). We would also like to thank the anonymous reviewers for their extensive comments, which have greatly improved the quality of the paper. The first author is supported by NWO grant 639.021.508.     

A note on the expressibility problem for modal logics and star-free regular expressions

The purpose of this note is to (i) raise attention for an interesting type of decision problem for logics, known under different names such as the expressibility problem and the uniform clone membership problem, (ii) disseminate a remarkable and powerful negative result of M.F. Ra?ǎ from the 1980s that seems to have escaped attention of many researchers, and (iii) show, with the help of Ra?ǎ's theorem, that the problem is undecidable for star-free regular expressions.In Section 1 we introduce the expressibility problem, taking Boolean formulas as an example. In Section 2, we present, and improve upon, Ra?ǎ's theorem for transitive modal logics. In Section 3, we derive, as a consequence of Ra?ǎ's theorem, the undecidability of the expressibility problem for star-free regular expressions. Finally, we conclude in Section 4 with some open questions.     

Phytochrome‐Based Extracellular Matrix with Reversibly Tunable Mechanical Properties

Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength‐specific, and dose‐ and space‐controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a poly(ethylene glycol) matrix, hydrogel materials responsive to light in the cell‐compatible red/far‐red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechanosignaling pathways respond to changing mechanical environments and to control the migration of primary immune cells in 3D. This optogenetics‐inspired matrix allows fundamental questions of how cells react to dynamic mechanical environments to be addressed. Further, remote control of such matrices can create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots.     

Remote‐Controlled Hydrogel Depots for Time‐Scheduled Vaccination

Remote‐controlled drug depots represent a highly valuable tool for the timely controlled administration of pharmaceuticals in a patient compliant manner. Here, the first pharmacologically controlled material that allows for the scheduled induction of a medical response in mice is described. To this aim, a novel, humanized biohybrid material that releases its cargo in response to a small‐molecule stimulus licensed for human use is developed. The functionality of the material in mice is demonstrated by the remote‐controlled delivery of a vaccine against the oncogenic human papillomavirus type 16. It is shown that the biohybrid depot‐mediated immunoprotection is equivalent to the classical multi‐injection‐based vaccination. These results indicate that this material can be used as a universal remote‐controlled vehicle for the patient‐compliant delivery of vaccines and pharmaceuticals.