Functional site prediction selects correct protein models

<p>Abstract</p> <p>Background</p> <p>The prediction of protein structure can be facilitated by the use of constraints based on a knowledge of functional sites. Without this information it is still possible to predict which residues are likely to be part of a functional site and this information can be used to select model structures from a variety of alternatives that would correspond to a functional protein.</p> <p>Results</p> <p>Using a large collection of protein-like decoy models, a score was devised that selected those with predicted functional site residues that formed a cluster. When tested on a variety of small <it>α</it>/<it>β</it>/<it>α </it>type proteins, including enzymes and non-enzymes, those that corresponded to the native fold were ranked highly. This performance held also for a selection of larger <it>α</it>/<it>β</it>/<it>α </it>proteins that played no part in the development of the method.</p> <p>Conclusion</p> <p>The use of predicted site positions provides a useful filter to discriminate native-like protein models from non-native models. The method can be applied to any collection of models and should provide a useful aid to all modelling methods from <it>ab initio </it>to homology based approaches.</p

Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts

BACKGROUND: Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction. RESULTS: Performance was measured on a test set consisting of about 50,000 abstracts from one year of MEDLINE. Synonyms retrieved from curated genomics databases were used as a gold standard. The system obtained a maximum F-score of 22.21% (23.18% precision and 21.36% recall), with high efficiency in the use of seed pairs. CONCLUSION: The method performs comparably with other studied methods, does not rely on sophisticated named-entity recognition, and requires little initial seed knowledge

Emerging Chirality in Artificial Spin Ice

Artificial spin ice, made up of planar nanostructured arrays of simple ferromagnetic bars, is a playground for rich physics associated with the spin alignment of the bars and spin texture associated with the magnetic frustration at the bar vertices. The phase diagram is exotic, showing magnetic monopole-like defects and liquid and solid phases of spins arranged in loop states with predicted chiral order. We show that magnetotransport measurements in connected honeycomb structures yield the onset of an anomalous Hall signal at 50 kelvin. The temperature scale can be attributed to the long-range dipolar ice phase. The topological Hall signal arises because chiral loops form at the sample edges, indicating a generic route to exotic states via nanoarray edge structure

The non-random walk of chiral magnetic charge carriers in artificial spin ice

The flow of magnetic charge carriers (dubbed magnetic monopoles) through frustrated spin ice lattices, governed simply by Coulombic forces, represents a new direction in electromagnetism. Artificial spin ice nanoarrays realise this effect at room temperature, where the magnetic charge is carried by domain walls. Control of domain wall path is one important element of utilizing this new medium. By imaging the transit of domain walls across different connected 2D honeycomb structures we contribute an important aspect which will enable that control to be realized. Although apparently equivalent paths are presented to a domain wall as it approaches a Y-shaped vertex from a bar parallel to the field, we observe a stark non-random path distribution, which we attribute to the chirality of the magnetic charges. These observations are supported by detailed statistical modelling and micromagnetic simulations. The identification of chiral control to magnetic charge path selectivity invites analogy with spintronics

Limitations in artificial spin ice path selectivity: the challenges beyond topological control

Magnetic charge is carried through nanowire networks by domain walls, and the micromagnetic structure of a domain wall provides an opportunity to manipulate its movement. We have shown previously that magnetic monopole defects exist in artificial spin ice (ASI) and result from two bar switching at a vertex. To create and manipulate monopole defects and indeed magnetic charge in general, path selectivity of the domain wall at a vertex is required. We have recently shown that in connected ASI structures, transverse wall chirality (or topology) determines wall path direction, but a mechanism known as Walker breakdown, where a wall mutates into a wall of opposite chirality partially destroys selectivity. Recently it has been claimed that in isolated Y-shaped junctions that support vortex walls, selectivity is entirely determined by chirality (or topology), the suggestion being that vortex wall chirality is robust in the Walker breakdown process. Here we demonstrate that in Y-shaped junctions, magnetic switching in the important topologically protected regime exists only for a narrow window of field and bar geometry, and that it will be challenging to access this regime in field-driven ASI. This work has implications for the wider field of magnetic charge manipulation for high density memory storage

Signatures of filamentary superconductivity in antiferromagnetic BaFe2As2 single crystals

In this paper, we present ac susceptibility and magnetotransport measurements on aged single crystals of the ferropnictide parent compound, BaFe2As2 with a paramagnetic-to-antiferromagnetic transition temperature of 134 K. The ac susceptibility shows the clear onset of a partial diamagnetic response with an onset temperature, commensurate with a subtle downturn in resistivity at approximately 20 K. Below 20 K the magnetotransport shows in-plane anisotropy, magnetic-field history dependence and a hysteretic signature. Above 20 K the crystals show the widely reported high-field linear magnetoresistance. An enhanced noise signature in ac susceptibility is observed above 20 K, which varies in character with amplitude and frequency of the ac signal. The hysteresis in magnetoresistance and the observed sensitivity of the superconducting phase to the amplitude of the ac signal are indicative characteristics of granular or weakly linked filamentary superconductivity. These features taken together with the observed noise signature above $T_{\mathrm{c}}$ suggests a link between the formation of the superconducting filamentary phase and the freezing of antiphase domain walls, known to exist in these materials

Leolani: a reference machine with a theory of mind for social communication

Our state of mind is based on experiences and what other people tell us. This may result in conflicting information, uncertainty, and alternative facts. We present a robot that models relativity of knowledge and perception within social interaction following principles of the theory of mind. We utilized vision and speech capabilities on a Pepper robot to build an interaction model that stores the interpretations of perceptions and conversations in combination with provenance on its sources. The robot learns directly from what people tell it, possibly in relation to its perception. We demonstrate how the robot's communication is driven by hunger to acquire more knowledge from and on people and objects, to resolve uncertainties and conflicts, and to share awareness of the per- ceived environment. Likewise, the robot can make reference to the world and its knowledge about the world and the encounters with people that yielded this knowledge.Comment: Invited keynote at 21st International Conference on Text, Speech and Dialogue, https://www.tsdconference.org/tsd2018

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Realization of ground state in artificial kagome spin ice via topological defect-driven magnetic writing

Arrays of non-interacting nanomagnets are widespread in data storage and processing. As current technologies approach fundamental limits on size and thermal stability, enhancing functionality through embracing the strong interactions present at high array densities becomes attractive. In this respect, artificial spin ices are geometrically frustrated magnetic metamaterials that offer vast untapped potential due to their unique microstate landscapes, with intriguing prospects in applications from reconfigurable logic to magnonic devices or hardware neural networks. However, progress in such systems is impeded by the inability to access more than a fraction of the total microstate space. Here, we demonstrate that topological defect-driven magnetic writing—a scanning probe technique—provides access to all of the possible microstates in artificial spin ices and related arrays of nanomagnets. We create previously elusive configurations such as the spin-crystal ground state of artificial kagome dipolar spin ices and high-energy, low-entropy ‘monopole-chain’ states that exhibit negative effective temperatures

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults