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.     

The development of railway safety in Finland

This study reviews the development of railway safety in Finland from 1959 to 2008. The results show that the level of safety has greatly improved over the past five decades. The total number of railway fatalities did not show any obvious decreasing or increasing trend during the first decade, but since the early 1970s the annual number of fatalities has decreased from about 100 to 20. The estimated overall annual reduction per year from 1970 to 2008 was 5.4% (with a 95% confidence interval from −8.2% to −2.6%). The reduction in subcategories per million train-kilometres from 1959 to 2008 was 4.4% per year for passengers, 8.3% for employees, 5.0% for road users at level crossings and 3.6% for others (mainly trespassers). The safety improvement for passengers and staff was probably influenced by the introduction of central locking of doors in passenger cars and improved procedures to protect railway employees working on the tracks. The number of road users killed at level crossings has fallen due to the installation of barriers and the construction of overpasses and underpasses at crossings with dense traffic, removal of level crossings, and an improvement of conditions such as visibility at crossings. The number of trespasser fatalities has seen the least decline. Key plans for the future include further reduction of the number of level crossings on the state railway network from the current roughly 3500–2200 by 2025, and involving communities in safety work related to railway trespassers.     

Enhancing Photovoltaic Performance Using an All‐Conjugated Random Copolymer to Tailor Bulk and Interfacial Morphology of the P3HT:ICBA Active Layer

Bulk heterojunction (BHJ) solar cells are fabricated using active material blends of poly(3‐hexylthiophene) (P3HT) donor, indene‐C₆₀ bisadduct (ICBA) acceptor, and an all‐conjugated random copolymer (RCP) additive. By optimizing RCP loading, power conversion efficiencies (PCEs) up to 20% higher than those of a binary P3HT:ICBA mixture are achieved. The improved device characteristics are rationalized in terms of the differences between the photoactive thin film morphologies. Energy‐filtered transmission electron micro­scopy reveals that incorporation of the RCP improves the degree of structural order of the BHJ fibrillar network and increases the extent of microphase separation between P3HT and ICBA. Additionally, a combination of atomic force microscopy and X‐ray photoelectron spectroscopy analysis indicates segregation of the RCP at the free interface, leading to a shift in the surface potentials measured by Kelvin probe force microscopy. These changes, both in the bulk morphology and in the interfacial composition/energetics, are correlated to improved carrier collection efficiency due to a reduction of non‐geminate recombination, which is measured by charge extraction of photo­generated carriers by linearly increasing voltage.     

In situ monitoring of the biocatalysed partial hydrolysis of cocoa butter and palm oil fraction

Partial glycerides are widely used ingredients in confectionery products that can be produced from natural fats. In a biocatalytic partial hydrolysis of cocoa butter and palm oil fractions, a product mixture containing 1.5% monoglycerides and 5.5% diglycerides intended for the use in confectionery products was created. This study is a proof of principle that shows the feasibility of monitoring the biocatalytic partial hydrolysis of these two natural fats in situ with ATR-FTIR spectroscopy. An economic approach was utilised for calibration since partial glyceride calibration standards are costly and poorly available. The released compounds were quantified by means of chemometric modelling, and the model was validated with gas chromatography. Resulting root mean square errors were in the low per cent range. Additionally, the results indicate that distinction of the released free fatty acids is possible with ATR-FTIR spectroscopy.     

Protection through property: from private to river-held rights

ABSTRACT

This article explores how private owners can protect bodies of water through private property rights. It compares the use of conventional property rights in the Netherlands and New Zealand with a novel approach whereby a New Zealand river owns itself.     

Living Materials Herald a New Era in Soft Robotics

Living beings have an unsurpassed range of ways to manipulate objects and interact with them. They can make autonomous decisions and can heal themselves. So far, a conventional robot cannot mimic this complexity even remotely. Classical robots are often used to help with lifting and gripping and thus to alleviate the effects of menial tasks. Sensors can render robots responsive, and artificial intelligence aims at enabling autonomous responses. Inanimate soft robots are a step in this direction, but it will only be in combination with living systems that full complexity will be achievable. The field of biohybrid soft robotics provides entirely new concepts to address current challenges, for example the ability to self‐heal, enable a soft touch, or to show situational versatility. Therefore, “living materials” are at the heart of this review. Similarly to biological taxonomy, there is a recent effort for taxonomy of biohybrid soft robotics. Here, an expansion is proposed to take into account not only function and origin of biohybrid soft robotic components, but also the materials. This materials taxonomy key demonstrates visually that materials science will drive the development of the field of soft biohybrid robotics.     

Handle mergers and acquisitions with care: the fragility of trust between the IT-service provider and end-users

Information technology (IT) implementation continues to be a challenging process for many organizations. The challenge is heightened when systems are changed due to mergers and acquisitions (M&A). The recent focus on IT-service management highlights the importance of having positive relationships between IT-service providers and end-users. In an M&A situation, there is often little history, and thus limited basis for trust in the IT organization, yet systems often need to be changed in these situations. The current study examines the IT-service provider’s relationship with the end-user to ascertain the factors that influence that relationship and ultimately influence end-user attitudes toward the new system. We study a mandated implementation following an acquisition in the banking industry. The results highlight the important and fragile nature of trust in the IT-service provider. In addition, the results demonstrate that there are significant differences in what matters at what time during the implementation process.     

No Neuromuscular Side-Effects of Scopolamine in Sensorimotor Control and Force-Generating Capacity Among Parabolic Fliers

Scopolamine is used to counteract motion sickness in parabolic flight (PF) experiments. Although the drug’s anticholinergic properties effectively impede vomiting, recent studies document other sensory side-effects in the central nervous system that may considerably influence sensorimotor performance. This study aimed to quantify such effects in order to determine if they are of methodological and operational significance for sensorimotor control. Ten subjects of a PF campaign received a weight-sex-based dose of a subcutaneous scopolamine injection. Sensorimotor performance was recorded before medication, 20min, 2h and 4h after injection in four space-relevant paradigms: balance control in one-leg stance with eyes open (protocol 1) and closed as well as force-generating capacity in countermovement jumps and hops (protocol 2). Postural sway, forces and joint angles were recorded. Neuromuscular control was assessed by electromyography and peripheral nerve stimulation; H-reflexes and M-waves were used to monitor spinal excitability of the Ia afferent reflex circuitry and maximal motor output. (1) H-reflex amplitudes, latencies and functional reflexes remained unchanged after scopolamine injection. (2) M-waves, neuromuscular activation intensities and antagonistic muscle coordination did not change with scopolamine administration. (3) Balance performance and force-generating capacity were not impeded by scopolamine. We found no evidence for changes in sensorimotor control in response to scopolamine injection. Sensory processing of daily relevant reflexes, spinal excitability, maximal motor output and performance parameters were not sensitive to the medication. We conclude that scopolamine administration can be used to counteract motion sickness in PF without methodological and operational concerns or interference regarding sensorimotor skills associated with neuromuscular control.