Effect of high-level content organizers on hypertext learning

This study investigates the cognitive abilities involved in hypertext learning and design approaches that can help users. We examined the effects of two types of high-level content organizers - a graphic spatial map and an alphabetical list - on readers’ memory for hypertext structure. In the control condition, a simple “home” page with no navigational aid was offered. Subjects were asked to read the hypertext with the purpose of learning the content, but in the post test phase they also had to recall the layout of nodes and links. Memory for links and page places varied as a function of condition. When a spatial map was available participants reconstructed more accurate formal structure then in the two other conditions. Participants’ memory about page places was the least accurate in the list condition. Results also indicate that participants use the content organizer when it is available in order to orientate during learning from hypertext documents.Our results prove that a content organizer showing the formal structure can facilitate the spatial mapping process. However, an organizer exposing a different structure than the real one would generate a conflict.     

Covalent Linkage and Macrocylization Preserve and Enhance Synergistic Interactions in Catalytic Amyloids

The self-assembly of short peptides into catalytic amyloid-like nanomaterials has proven to be a powerful tool in both understanding the evolution of early proteins and identifying new catalysts for practically useful chemical reactions. Here we demonstrate that both parallel and antiparallel arrangements of β-sheets can accommodate metal ions in catalytically productive coordination environments. Moreover, synergistic relationships, identified in catalytic amyloid mixtures, can be captured in macrocyclic and sheet-loop-sheet species, that offer faster rates of assembly and provide more complex asymmetric arrangements of functional groups, thus paving the way for future designs of amyloid-like catalytic proteins. Our findings show how initial catalytic activity in amyloid assemblies can be propagated and improved in more-complex molecules, providing another link in a complex evolutionary chain between short, potentially abiotically produced peptides and modern-day enzymes.     

Constraint-Based Facial Animation

Constraints have been traditionally used for computer animation applications to define side conditions for generating synthesized motion according to a standard, usually physically realistic, set of motion equations. The case of facial animation is very different, as no set of motion equations for facial expressions is available. In this paper we discuss a facial animation editor, which uses numerical constraints for two roles: to declare the mimic repertoire of synthetic faces and other requirements a facial animation has to meet, and to aid the animator in the process of composing a specific animation fulfilling the requirements. The editor is thus also a ``motion sculpturing' tool, which lifts the task of creating facial animation from the control data manipulation level to the conceptual design level. The major aid of the editor is to repair inconsistencies due to changes made by the user, and revise changes for which no good repair is possible. Also, reuse of constrained animations, especially expressions, is supported. The main machinery behind these services is interval propagation, which, if using certain type of linear inequalities to express the character- as well as the animation-specific requirements, can produce quickly the interval of feasible values for each control variable. If a solution (usually, repair) has to be produced, it is generated by selecting the best one from a restricted set of acceptable solutions, based on user-defined or automatically generated criteria for the choices.     

Topical Liposomal local Anesthetics: Design, Optimization and Evaluation of Formulations

To improve the rate of penetration into the skin, and to develop an effective topical anesthetic product, selected local anesthetic agents, benzocaine, lidocaine, dibucaine, etidocaine and tetracaine were encapsulated into liposomes using the solvent evaporation method. After the pilot experiments, tetracaine was selected for further development. Encapsulation efficiency was determined by centrifugation of liposomes and spectrophotometric analysis of liposome pellets and supernatants. Physical stability and organoleptic properties of the various liposomal tetracaine formulas were monitored visually and by microscopy for 1 year. Tetracaine was found to be suitable for the development of a liposomal drug delivery system with high encapsulation efficiency (60-90%) and physical stability. The results showed that encapsulation efficiency of tetracaine into liposomes can be increased by increasing drug concentration and pH, and including negatively charged stearic acid or unsaturated lipids in the formula. Stability of tetracaine increased with higher encapsulation efficiency, however the shelf life of the product was still short (2 months). In-process and finished product quality control parameters are suggested to facilitate the topical liposomal product development in general.     

Liposome encapsulated prostaglandin E1 in erectile dysfunction: correlation between in vitro delivery through foreskin and efficacy in patients

Serial 3D MR scan pairs (1 year intervals) from nine control subjects and nine Alzheimer disease (AD) patients were matched using an accurate fast fluid algorithm. Subtraction of matched scans indicated near complete cancellation of brain structure; mean cross-correlation coefficients were 0.946 (controls) and 0.933 (AD). In the AD group, regions of expansion and contraction in the deformation field were consistent with the known patterns of tissue loss and expansion of CSF spaces. Fluid registration may permit better localization of structural change.     

A critical review on questionnaire surveys in the field of energy-related occupant behaviour

Occupants perform various actions to satisfy their physical and non-physical needs in buildings. These actions greatly affect building operations and thus energy use. Clearly understanding and accurately modelling occupant behaviour in buildings are crucial to guide energy-efficient building design and operation, and to reduce the gap between design and actual energy performance of buildings. To study and understand occupant behaviour, a cross-sectional questionnaire survey is one of the most useful tools to gain insights on general behaviour patterns and drivers, and to find connections between human, social and local comfort parameters. In this study, 33 projects were reviewed from the energy-related occupant behaviour research literature that employed cross-sectional surveys or interviews for data collection from the perspective of findings, limitations and methodological challenges. This research shows that future surveys are needed to bridge the gaps in literature but they would need to encompass a multidisciplinary approach to do so as until now only environmental and engineering factors were considered in these studies. Insights from social practice theories and techniques must be acquired to deploy robust and unbiased questionnaire results, which will provide new, more comprehensive knowledge in the field, and therefore occupant behaviour could be better understood and represented in building performance simulation to support design and operation of low or net-zero energy buildings.     

Effect of IL-4 and IL-12 liposomal formulations on the induction of immune response to bovine herpesvirus type-1 glycoprotein D

Activation of different T-helper (Th) responses following immunisation has profound and specific influences on the development of the immune response and on the ability of a vaccine to confer protection. Since cytokines are capable of influencing the stimulation of distinct T-cell responses, their encapsulation in vaccines should modulate antigen-specific immune responses. Unfortunately, the use of cytokines in vivo is hampered by their rapid clearance and inactivation. One possible solution to this problem is the use of liposomes to entrap both cytokines and antigen. This approach will not only protect the cytokine but will also deliver the two components simultaneously to the same site. The authors examined, therefore, the immune responses elicited by systemic immunisation of mice with liposome formulations containing a truncated form of bovine herpesvirus type-1 glycoprotein D (tgD) together with IL-4 or IL-12. Subcutaneous immunisation with liposomes containing tgD and IL-12 significantly enhanced the induction of antigen-specific cellular and humoral immune responses. These responses were characterised by an increase in IFN-gamma secreting cells and the induction of tgD-specific IgG2a antibodies. In contrast, encapsulation of IL-4 into tgD-liposomes did not enhance the humoral immune response to gD but significantly influenced the development of antigen-specific IL-4 secreting cells. Our results indicated that encapsulation of IL-12 into the liposomes was necessary for the systemic adjuvant effect and demonstrated the feasibility of using liposome technology and cytokines to manipulate the development of different antigen-specific Th subsets in vivo.     

GDNF Increases Inhibitory Synaptic Drive on Principal Neurons in the Hippocampus via Activation of the Ret Pathway

Glial cell line-derived neurotrophic factor (GDNF) has been shown to counteract seizures when overexpressed or delivered into the brain in various animal models of epileptogenesis or chronic epilepsy. The mechanisms underlying this effect have not been investigated. We here demonstrate for the first time that GDNF enhances GABAergic inhibitory drive onto mouse pyramidal neurons by modulating postsynaptic GABA_A receptors, particularly in perisomatic inhibitory synapses, by GFRα1 mediated activation of the Ret receptor pathway. Other GDNF receptors, such as NCAM or Syndecan3, are not contributing to this effect. We observed similar alterations by GDNF in human hippocampal slices resected from epilepsy patients. These data indicate that GDNF may exert its seizure-suppressant action by enhancing GABAergic inhibitory transmission in the hippocampal network, thus counteracting the increased excitability of the epileptic brain. This new knowledge can contribute to the development of novel, more precise treatment strategies based on a GDNF gene therapy approach.     

Smart building management vs. intuitive human control—Lessons learnt from an office building in Hungary

Smart building management and control are adopted nowadays to achieve zero-net energy use in buildings. However, without considering the human dimension, technologies alone do not necessarily guarantee high performance in buildings. An office building was designed and built according to state-of-the-art design and energy management principles in 2008. Despite the expectations of high performance, the owner was facing high utility bills and low user comfort in the building located in Budapest, Hungary. The objective of the project was to evaluate the energy performance and comfort indices of the building, to identify the causes of malfunction and to elaborate a comprehensive energy concept. Firstly, current building conditions and operation parameters were evaluated. Our investigation found that the state-of-the-art building management system was in good conditions but it was operated by building operators and occupants who are not aware of the building management practice. The energy consumption patterns of the building were simulated with energy modelling software. The baseline model was calibrated to annual measured energy consumption, using actual occupant behaviour and presence, based on results of self-reported surveys, occupancy sensors and fan-coil usage data. Realistic occupant behaviour models can capture diversity of occupant behaviour and better represent the real energy use of the building. This way our findings and the effect of our proposed improvements could be more reliable. As part of our final comprehensive energy concept, we proposed intervention measures that would increase indoor thermal comfort and decrease energy consumption of the building. A parametric study was carried out to evaluate and quantify energy, comfort and return on investment of each measure. It was found that in the best case the building could save 23% of annual energy use. Future work includes the follow-up of: occupant reactions to intervention measures, the realized energy savings, the measurement of occupant satisfaction and behavioural changes.     

Synergistic Interactions Are Prevalent in Catalytic Amyloids

Interactions between multiple functional groups are key to catalysis. Previously, we reported synergistic interactions in catalytic amyloids formed by mixtures of heptameric peptides that lead to significant improvements in esterase activity. Herein, we describe the in-depth investigation of synergistic interactions within a family of amyloid fibrils, exploring the results of functional group interactions, the effects of chirality and the use of mixed enantiomers within fibrils. Remarkably, we find that synergistic interactions (either positive or negative) are found in the vast majority of binary mixtures of catalytic amyloid-forming peptides. The productive arrangements of functionalities rapidly identified by mixing different peptides will undoubtedly lead to the development of more active catalysts for a variety of different transformations.