Discovery of Heterocyclic Nonacetamide Synaptic Vesicle Protein 2A (SV2A) Ligands with Single‐Digit Nanomolar Potency: Opening Avenues towards the First SV2A Positron Emission Tomography (PET) Ligands

The role of the synaptic vesicle protein 2A (SV2A) protein, target of the antiepileptic drug levetiracetam, is still mostly unknown. Considering its potential to provide in vivo functional insights into the role of SV2A in epileptic patients, the development of an SV2A positron emission tomography (PET) tracer has been undertaken. Using a 3D pharmacophore model based on close analogues of levetiracetam, we report the rationale design of three heterocyclic non‐acetamide lead compounds, UCB‐A, UCB‐H and UCB‐J, the first single‐digit nanomolar SV2A ligands with suitable properties for development as PET tracers.     

Optimization methods for improving IP-level fast protection for local shared risk groups with Loop-Free Alternates

Lately, demand for fast failure recovery in IP networks has become compelling. The Loop-Free Alternates (LFA) specification is a simple IP Fast ReRoute (IPFRR) scheme proposed by the IETF that does not require profound changes to the network infrastructure before deployment. However, this simplicity comes at a severe price, because LFA does not provide complete protection for all possible failure cases in a general topology. This is even more so if network components are prone to fail jointly. In this paper, we study an important network optimization problem arising in this context, the so called LFA graph extension problem, which asks for augmenting the topology with new links in an attempt to improve the LFA failure case coverage. Unfortunately, this problem is NP-complete. The main contributions of the paper are a novel extension of the bipartite graph model for the LFA graph extension problem to the multiple-failure case using the model of Shared Risk Groups, and a suite of accompanying heuristics to obtain approximate solutions. We also compare the performance of the algorithms in extensive numerical studies and we conclude that the optimum can be approximated well in most cases relevant to practice.     

LaMgAl11O19 synthesis using non-hydrolytic sol-gel methods

Polycrystalline LaMgAl₁₁O₁₉ (LMA) was prepared by four different non-hydrolytic sol-gel methods. From stable solutions, four powder precursors containing an amorphous and nanocrystalline phase with specific reactivity were obtained. The particle size, morphology, thermal behaviour, and phase composition of the powder precursors were studied using DLS, TEM, DSC/TG and XRD. Bulk ceramic samples containing LMA were prepared at 1200?°C for 16?h and examined in terms of phase purity and microstructure using XRD, SEM, and TEM. Raman spectroscopy of pure LMA was used to study the structure in detail. A mechanism of LMA formation and a relation between powder precursor properties and final phase composition is proposed. These findings may be useful for designing modern technologies for fabrication of LMA for optical or protective coating applications.     

Internal and external factors of competitiveness shaping the future of wooden multistory construction in Finland and Sweden

In transitioning to a renewable material-based bio economy, growing public and industry interest is apparent for using wooden multistory construction (WMC) as a sustainable urban housing solution in Europe, but its business implications are not well understood. In our study, we evaluate, which internal and external factors of competitiveness are shaping the future of WMC, especially in the context of Finland and Sweden. Based on a multi-level perspective of socio-technical transitions, we conducted a three-stage dissensus-based Delphi study. The identified internal and external factors affecting the future competitiveness of the WMC business emphasize the importance of skilled architects and builders and the role of standardized building systems. Based on our results, the key aspects influencing the future competitiveness of WMC in the region are related to the development of technical infrastructure and project-based business networks, while additional changes in regulatory framework are perceived as less important. We conclude that towards 2030, the strong cognitive rules founded in the concrete-based building culture in these countries is likely to inhibit the dynamics of the socio-technical regime level. A change is also needed in the WMC business culture towards more open cross-sectoral collaboration and new business networks between different-sized players.     

Repeated thermo-hydrolytic disintegration of medium density fibreboards (MDF) for the production of new MDF

European Journal of Wood and Wood Products - Medium density fibreboards (MDF) are currently not recycled after service life, but various publications report on recycling by the disintegration of...     

Experiences in building a Grid-based platform to serve Earth observation training activities

Earth observation data processing and storing can be done nowadays only using distributed systems. Experiments dealing with a large amount of data are possible within the timeframe of a lesson and can give trainees the freedom to innovate. Following these trends and ideas, we have built a proof-of-the-concept platform, named GiSHEO, for Earth observation educational tasks. It uses Grid computing technologies to analyze and store remote sensing data, and combines them with eLearning facilities. This paper provides an overview of the GiSHEO's platform architecture and of its technical and innovative solutions.     

Using enzymatic numerical P systems for modeling mobile robot controllers

P systems (PSs) are powerful computing models based on the structure of a biological cell and on the way chemicals interact in complex biochemical reactions which take place in various compartments (or membranes) of the cell. A lot of interest has been focused on developing various forms of PSs, from cell-like to tissue-like structures. Most of the research effort has been concentrated on symbolical PSs. Numerical P systems (NPSs) have been introduced in 2006 for possible applications in economics and business processes but no other structures and applications concerning this type of PSs have been provided since then. This paper proposes a new class of NPSs, in which enzyme-like variables allow the existence of more than one production function in each membrane, while keeping the deterministic nature of the system. The way this new type of deterministic NPSs works and a possible use of it for modeling mobile robot controllers are detailed.     

Internal preference mapping and the issue of satiety

Internal preference mapping (IPM) and Landscape Segmentation Analysis® (LSA) are two techniques broadly used to unfold consumers’ overall product liking ratings and create spatial maps that will provide further insights on consumers’ preferences. IPM is based on a vector model while LSA involves an ideal point model. Through a simulation and the analysis of 27 market research data sets, it is shown that IPM consistently creates a hedonic dimension that prevents the identification of satiety prone attributes (intensities higher or lower than a optimal level being disliked by the consumers) on that dimension. As a result, subsequent steps taken upon generating an IPM map such as the investigation of drivers of liking, population segmentation and the estimation of optimal product profiles have also a strong likelihood of resulting in distorted results, the level of distortion being dependent on the actual configuration of the underlying structure that IPM tried to uncover. It is also shown that a technique based on ideal points such as LSA does not exhibit this systematic artifact when unfolding liking data. Consequently, sensory scientists and market researchers should use caution when interpreting and using results issued from an internal preference mapping analysis.