Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers

Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer’s disease (AD). We started with five peptides (¹⁵QKLVFF²⁰, ¹⁶KLVFF²⁰, ¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and ¹⁵QKLV¹⁸), to which 14 different organic acids were attached at the N-terminal. It was necessary to evaluate the physiochemical features of these sequences due to the biological correlation with our proposal. Hence, the preliminary analysis of different pharmacological features provided the necessary data to select the peptides with the best biocompatibility for administration purposes. Our approaches demonstrated that the peptides ¹⁷LVFF²⁰, NA-¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and NA-¹⁶KLVF¹⁹ (NA-nicotinic acid) have the ability to interfere with fibril formation and hence improve the neuro and cognitive functions. Moreover, the peptide conjugate NA-¹⁶KLVF¹⁹ possesses attractive pharmacological properties, demonstrated by in silico and in vitro studies. Tandem mass spectrometry showed no fragmentation for the spectra of ¹⁶KLVF¹⁹. Such important results suggest that under the action of protease, the peptide cleavage does not occur at all. Additionally, circular dichroism confirmed docking simulations and showed that NA-¹⁶KLVF¹⁹ may improve the β-sheet breaker mechanism, and thus the entanglement process of amyloid-beta peptides can be more effective.     

Evolutionary algorithms for continuous-space optimisation

From a global viewpoint, evolutionary algorithms (EAs) working on continuous search-spaces can be regarded as homogeneous Markov chains (MCs) with discrete time and continuous state. We analyse from this viewpoint the (1?+?1)EA on the inclined plane fitness landscape, and derive a closed-form expression for the probability of occupancy of an arbitrary target zone, at an arbitrary iteration of the EA. For the hitting-time of an arbitrary target zone, we provide lower and upper bounds, as well as an asymptotic limit. Discretization leads to an MC with discrete time, whose simple structure is exploited to carry out efficient numerical investigations of the theoretical results obtained. The numerical results thoroughly confirm the theoretical ones, and also suggest various conjectures which go beyond the theory.     

Recording of time-varying back-pain data: a wireless solution.

Chronic back pain is a debilitating experience for a considerable proportion of the adult population, with a significant impact on countries' economies and health systems. While there has been increasing anecdotal evidence to support the fact that for certain categories of patients (such as wheelchair users), the back pain experienced is dynamically varying with time, there is a relative scarcity of data to support and document this observation, with consequential impact upon such patients' treatment and care. Part of the reason behind this state of affairs is the relative difficulty in gathering pain measurements at precisely defined moments in time. In this paper, we describe a wireless-enabled solution that collects both questionnaire and diagrammatic, visual-based data, via a pain drawing, which overcomes such limitations, enabling seamless data collection and its upload to a hospital server using existing wireless fidelity technology. Results show that it is generally perceived to be an easy-to-use and convenient solution to the challenges of anywhere/anytime data collection.     

Trust model for certificate revocation in ad hoc networks

In this paper we propose a distributed trust model for certificate revocation in ad hoc networks. The proposed model allows trust to be built over time as the number of interactions between nodes increase. Furthermore, trust in a node is defined not only in terms of its potential for maliciousness, but also in terms of the quality of the service it provides. Trust in nodes where there is little or no history of interactions is determined by recommendations from other nodes. If the nodes in the network are selfish, trust is obtained by an exchange of portfolios. Bayesian networks form the underlying basis for this model.     

A High-Throughput Screening System Based on Fluorescence-Activated Cell Sorting for the Directed Evolution of Chitinase A

Chitinases catalyze the degradation of chitin, a polymer of N-acetylglucosamine found in crustacean shells, insect cuticles, and fungal cell walls. There is great interest in the development of improved chitinases to address the environmental burden of chitin waste from the food processing industry as well as the potential medical, agricultural, and industrial uses of partially deacetylated chitin (chitosan) and its products (chito-oligosaccharides). The depolymerization of chitin can be achieved using chemical and physical treatments, but an enzymatic process would be more environmentally friendly and more sustainable. However, chitinases are slow-acting enzymes, limiting their biotechnological exploitation, although this can be overcome by molecular evolution approaches to enhance the features required for specific applications. The two main goals of this study were the development of a high-throughput screening system for chitinase activity (which could be extrapolated to other hydrolytic enzymes), and the deployment of this new method to select improved chitinase variants. We therefore cloned and expressed the Bacillus licheniformis DSM8785 chitinase A (chiA) gene in Escherichia coli BL21 (DE3) cells and generated a mutant library by error-prone PCR. We then developed a screening method based on fluorescence-activated cell sorting (FACS) using the model substrate 4-methylumbelliferyl β-d-N,N′,N″-triacetyl chitotrioside to identify improved enzymes. We prevented cross-talk between emulsion compartments caused by the hydrophobicity of 4-methylumbelliferone, the fluorescent product of the enzymatic reaction, by incorporating cyclodextrins into the aqueous phases. We also addressed the toxicity of long-term chiA expression in E. coli by limiting the reaction time. We identified 12 mutants containing 2–8 mutations per gene resulting in up to twofold higher activity than wild-type ChiA.     

Correction to: Towards developing digital interventions supporting empathic ability for children with autism spectrum disorder

Universal Access in the Information Society - It is very challenging for children with autism to express their emotions to others as well as to recognise others’ feelings accurately. As...     

Fracture toughness of autoclaved aerated concrete

So far, few experiments to determine fracture toughness of autoclaved aerated concrete have been reported in the literature. Tests on three different types of autoclaved aerated concrete using six different specimen geometries have been carried out. Four of the six specimen geometries chosen lead to nearly identical results for K_IC. The two other types of specimen were used to determine fracture energy G_f. K_IC increases with compressive strength of the material. Fracture energy is about one tenth of the corresponding value of normal concrete. The influence of rate of loading on K_IC can be expressed by means of a power law. These results suggest that linear elastic fracture mechanics is a suitable approximation for the calculation of crack propagation in autoclaved aerated concrete.     

PainDroid: an android-based virtual reality application for pain assessment

Earlier studies in the field of pain research suggest that little efficient intervention currently exists in response to the exponential increase in the prevalence of pain. In this paper, we present an Android application (PainDroid) with multimodal functionality that could be enhanced with Virtual Reality (VR) technology, which has been designed for the purpose of improving the assessment of this notoriously difficult medical concern. PainDroid has been evaluated for its usability and acceptability with a pilot group of potential users and clinicians, with initial results suggesting that it can be an effective and usable tool for improving the assessment of pain. Participant experiences indicated that the application was easy to use and the potential of the application was similarly appreciated by the clinicians involved in the evaluation. Our findings may be of considerable interest to healthcare providers, policy makers, and other parties that might be actively involved in the area of pain and VR research.     

Software development methods and usability: Perspectives from a survey in the software industry in Norway

This paper investigates the relationship between software development methodologies and usability. The point of departure is the assumption that two important disciplines in software development, one of software development methods (SDMs) and one of usability work, are not integrated in industrial software projects.

Building on previous research we investigate two questions; (1) Will software companies generally acknowledge the importance of usability, but not prioritise it in industrial projects? and (2) To what degree are software development methods and usability perceived by practitioners as being integrated? To this end a survey in the Norwegian IT industry was conducted. From a sample of 259 companies we received responses from 78 companies.

In response to our first research question, our findings show that although there is a positive bias towards usability, the importance of usability testing is perceived to be much less than that of usability requirements. Given the strong time and cost pressures associated with the software industry, we believe that these results highlight that there is a gap between intention and reality. Regarding our second research question our survey revealed that companies perceive usability and software development methods to be integrated. This is in contrast to earlier research, which, somewhat pessimistically, has argued for the existence of two different cultures, one of software development and one of usability. The findings give hope for the future, in particular because the general use of system development methods are pragmatic and adaptable.