Simplifying responsible research and innovation – a tool building in societal readiness into research

Researchers and research funders are increasingly seeking to ensure their work is aligned to societal needs and to prevent it from having foreseeable negative impacts, particularly in fast moving and ethically sensitive fields. In this post, Stefan de Jong, Michael J. Bernstein and Ingeborg Meijer, describe their work developing a tool that facilitates researchers and research funders to incorporate responsible research and innovation values into their work

Genomic alterations in primary gastric adenocarcinomas correlate with clinicopathological characteristics and survival.

Background & aimsPathogenesis of gastric cancer is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. In order to investigate the patterns of chromosomal aberrations in gastric carcinomas, we performed genome-wide microarray based comparative genomic hybridisation (microarray CGH). With this recently developed technique chromosomal aberrations can be studied with high resolution and sensitivity.MethodsArray CGH was applied to a series of 35 gastric adenocarcinomas using a genome-wide scanning array with 2275 BAC and P1 clones spotted in triplicate. Each clone contains at least one STS for linkage to the sequence of the human genome. These arrays provide an average resolution of 1.4 Mb across the genome. DNA copy number changes were correlated with clinicopathological tumour characteristics as well as survival.ResultsAll thirty-five cancers showed chromosomal aberrations and 16 of the 35 tumours showed one or more amplifications. The most frequent aberrations are gains of 8q24.2, 8q24.1, 20q13.12, 20q13.2, 7p11.2, 1q32.3, 8p23.1-p23.3, losses of 5q14.1, 18q22.1, 19p13.12-p13.3, 9p21.3-p24.3, 17p13.1-p13.3, 13q31.1, 16q22.1, 21q21.3, and amplifications of 7q21-q22, and 12q14.1-q21.1. These aberrations were correlated to clinicopathological characteristics and survival. Gain of 1q32.3 was significantly correlated with lymph node status (p=0.007). Tumours with loss of 18q22.1, as well as tumours with amplifications were associated with poor survival (p=0.02, both).ConclusionsMicroarray CGH has revealed several chromosomal regions that have not been described before in gastric cancer at this frequency and resolution, such as amplification of at 7q21-q22 and 12q14.1-q21.1, as well gains at 1q32.3, 7p11.2, and losses at 13q13.1. Interestingly, gain of 1q32.3 and loss of 18q22.1 are associated with a bad prognosis indicating that these regions could harbour gene(s) that may determine aggressive tumour behaviour and poor clinical outcome

LTSmin: high-performance language-independent model checking

In recent years, the LTSmin model checker has been extended with support for several new modelling languages, including probabilistic (Mapa) and timed systems (Uppaal). Also, connecting additional language front-ends or ad-hoc state-space generators to LTSmin was simplified using custom C-code. From symbolic and distributed reachability analysis and minimisation, LTSmin’s functionality has developed into a model checker with multi-core algorithms for on-the-fly LTL checking with partial-order reduction, and multi-core symbolic checking for the modal μ calculus, based on the multi-core decision diagram package Sylvan.\ud In LTSmin, the modelling languages and the model checking algorithms are connected through a Partitioned Next-State Interface (Pins), that allows to abstract away from language details in the implementation of the analysis algorithms and on-the-fly optimisations. In the current paper, we present an overview of the toolset and its recent changes, and we demonstrate its performance and versatility in two case studies

A new design for a traveling-wave Zeeman decelerator: II. Experiment

A novel traveling-wave Zeeman decelerator based on a double-helix coil geometry capable of decelerating paramagnetic molecules with high efficiency is presented. Moving magnetic traps are generated by applying time-dependent currents through the decelerator coils. Paramagnetic molecules in low-field-seeking Zeeman states are confined inside the moving traps which are decelerated to lower forward velocities. As a prototypical example, we demonstrate the deceleration of OH radicals from an initial velocity of 445 m s(-1) down to various final velocities. The experimental results are analyzed and numerically reproduced with the help of trajectory simulations confirming the phase-space stability and efficiency of the deceleration of the molecules in the new device

Functionalization of Supramolecular Polymers by Dynamic Covalent Boroxine Chemistry

Molecular scaffolds that enable the combinatorial synthesis of new supramolecular building blocks are promising targets for the construction of functional molecular systems. Here, we report a supramolecular scaffold based on boroxine that enables the formation of chiral and ordered 1D supramolecular polymers, which can be easily functionalized for circularly polarized luminescence. The boroxine monomers are quantitatively synthesized in situ, both in bulk and in solution, from boronic acid precursors and cooperatively polymerize into 1D helical aggregates stabilized by threefold hydrogen-bonding and π–π stacking. We then demonstrate amplification of asymmetry in the co-assembly of chiral/achiral monomers and the co-condensation of chiral/achiral precursors in classical and in situ sergeant-and-soldiers experiments, respectively, showing fast boronic acid exchange reactions occurring in the system. Remarkably, co-condensation of pyrene boronic acid with a hydrogen-bonding chiral boronic acid results in chiral pyrene aggregation with circularly polarized excimer emission and g-values in the order of 10−3. Yet, the electron deficiency of boron in boroxine makes them chemically addressable by nucleophiles, but also sensitive to hydrolysis. With this sensitivity in mind, we provide first insights into the prospects offered by boroxine-based supramolecular polymers to make chemically addressable, functional, and adaptive systems.</p

Photo-enhanced magnetization in Fe-doped ZnO nanowires

An emerging branch of electronics, the optospintronics, would be highly boosted if the control of magnetic order by light is implemented in magnetic semiconductors’ nanostructures being compatible with the actual technology. Here, we show that the ferromagnetic magnetization of low Fe-doped ZnO nanowires prepared by carbothermal process is enhanced under illumination up to temperatures slightly below room temperature. This enhancement is related to the existence of an oxygen vacancy VO in the neighborhood of an antiferromagnetic superexchange Fe3+-Fe3+ pair. Under illumination, the VO is ionized to to V+O giving an electron to a closeFe3+ ion from the antiferromagnetic pair. This light excited electron transition allows the transition of Fe3+ to Fe2+ forming stable ferromagnetic double exchange pairs, increasing the total magnetization. The results presented here indicate an efficient way to influence the magnetic properties of ZnO based nanostructures by light illumination at high temperatures

Reduced Plasticity in Coupling Strength in the Aging SCN Clock as Revealed by Kuramoto Modeling

The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consists of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase coherence of the neurons is plastic and driven by the duration of daylight. With aging, the capacity to behaviorally adapt to seasonal changes in photoperiod reduces. The mechanisms underlying photoperiodic adaptation are largely unknown, but are important to unravel for the development of novel interventions to improve the quality of life of the elderly. We analyzed the phase coherence of single-cell PERIOD2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN of young and old mice entrained to either long or short photoperiod. The phase coherence was used as input to a 2-community noisy Kuramoto model to estimate the coupling strength between and within neuronal subpopulations. The model revealed a correlation between coupling strength and photoperiod-induced changes in the phase relationship among neurons, suggesting a functional link. We found that the SCN of young mice adapts in coupling strength over a large range, with weak coupling in long photoperiod (LP) and strong coupling in short photoperiod (SP). In aged mice, we also found weak coupling in LP, but a reduced capacity to reach strong coupling in SP. The inability to respond with an increase in coupling strength suggests that manipulation of photoperiod is not a suitable strategy to enhance clock function with aging. We conclude that the inability of aged mice to reach strong coupling contributes to deficits in behavioral adaptation to seasonal changes in photoperiod. Circadian clocks in health and diseas