What makes it work? Exploring experiences of patient research partners and researchers involved in a long-term co-creative research collaboration

Background: Exchanging experiences of patient and public involvement (PPI) can bring insights into why, how and when PPI is most effective. The aim of this study was to explore the experiences of patient research partners (PRPs) and researchers engaged in a co-creative long-term collaboration in cancer research. Methods: The aim and procedures of this study were jointly decided upon by PRPs and researchers. The PRPs included former patients treated for cancer and significant others of the same target group. The participants (11 PRPs, 6 researchers) took part in semi-structured telephone interviews. The interviews were analysed using qualitative content analysis by a researcher who had no prior relationships with the participants. Results: Five overarching categories were identified: Reasons for investing in a long-term collaboration, Benefits of participating, Improving the research, Elements of success and Challenges and ways to improve. Reasons for investing in the collaboration included the desire to improve cancer care and to make use of own negative experiences. Benefits of participating included a positive impact on the PRPs' psychosocial adjustment to the illness. Moreover, the researchers highlighted that working together with the PRPs made the research feel more meaningful. The participants reported that the collaboration improved the relevance and acceptability of the research. Having a shared goal, a clear but yet accommodating structure, as well as an open and trustful working atmosphere were recognised as elements of success. The PRPs furthermore emphasized the importance of seeing that their input mattered. Among the few challenges raised were the distance to the meeting venues for some PRPs and a limited diversity among participants. Conclusions: This study identified factors essential to researchers and clinicians attempting to engage the public in research. Our results suggest that for successful patient involvement, the purpose and format of the collaboration should be clear to both PRPs and researchers. A clear but yet accommodating structure and keen leadership emerged as key factors to create a sense of stability and a trustful atmosphere. Furthermore, providing regular feedback on how PRPs input is implemented is important for PRPs to stay committed over time

Antimicrobial Activity of Human Prion Protein Is Mediated by Its N-Terminal Region

BACKGROUND: Cellular prion-related protein (PrP(c)) is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c), and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c) could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking) liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense

Determinisitic Optical Fock State Generation

We present a scheme for the deterministic generation of N-photon Fock states from N three-level atoms in a high-finesse optical cavity. The method applies an external laser pulsethat generates an $N$-photon output state while adiabatically keeping the atom-cavity system within a subspace of optically dark states. We present analytical estimates of the error due to amplitude leakage from these dark states for general N, and compare it with explicit results of numerical simulations for N \leq 5. The method is shown to provide a robust source of N-photon states under a variety of experimental conditions and is suitable for experimental implementation using a cloud of cold atoms magnetically trapped in a cavity. The resulting N-photon states have potential applications in fundamental studies of non-classical states and in quantum information processing.Comment: 25 pages, 9 figure

Multi-objective evolutionary algorithms and hyper-heuristics for wind farm layout optimisation

Wind farm layout optimisation is a challenging real-world problem which requires the discovery of trade-off solutions considering a variety of conflicting criteria, such as minimisation of the land area usage and maximisation of energy production. However, due to the complexity of handling multiple objectives simultaneously, many approaches proposed in the literature often focus on the optimisation of a single objective when deciding the locations for a set of wind turbines spread across a given region. In this study, we tackle a multi-objective wind farm layout optimisation problem. Different from the previously proposed approaches, we are applying a high-level search method, known as selection hyper-heuristic to solve this problem. Selection hyper-heuristics mix and control a predefined set of low-level (meta)heuristics which operate on solutions. We test nine different selection hyper-heuristics including an online learning hyper-heuristic on a multi-objective wind farm layout optimisation problem. Our hyper-heuristic approaches manage three well-known multi-objective evolutionary algorithms as low-level metaheuristics. The empirical results indicate the success and potential of selection hyper-heuristics for solving this computationally difficult problem. We additionally explore other objectives in wind farm layout optimisation problems to gain a better understanding of the conflicting nature of those objectives

Sonic hedgehog is a polarized signal for motor neuron regeneration in adult zebrafish

In contrast to mammals, the spinal cord of adult zebrafish has the capacity to reinitiate generation of motor neurons after a lesion. Here we show that genes involved in motor neuron development, i.e. the ventral morphogen sonic hedgehog a (shha), as well as the transcription factors nkx6.1 and pax6, together with a Tg(olig2:egfp) transgene, are expressed in the unlesioned spinal cord of adult zebrafish. Expression is found in ependymo-radial glial cells lining the central canal in ventro-dorsal positions that match expression domains of these genes in the developing neural tube. Specifically, Tg(olig2:egfp)(+) ependymo-radial glial cells, the adult motor neuron progenitors, co-express Nkx6.1 and Pax6, thus defining an adult motor neuron progenitor (pMN)-like zone. Shha is expressed in distinct ventral ependymo-radial glial cells. After a lesion, expression of all these genes is strongly increased, while relative spatial expression domains are maintained. In addition, expression of the hedgehog (hh) receptors patched1 and smoothened becomes detectable in ependymo-radial glial cells including those of the pMN-like zone. Cyclopamine-induced knock down of hh signaling significantly reduces ventricular proliferation and motor neuron regeneration. Expression of indicator genes for the FGF and retinoic acid signaling pathways was also increased in the lesioned spinal cord. This suggests that a sub-class of ependymo-radial glial cells retain their identity as motor neuron progenitors into adulthood and are capable of reacting to an shh signal and potentially other developmental signals with motor neuron regeneration after a spinal lesion

Designing a memorial place

The design and selection of a memorial stone and the site of the grave, both of which represent the deceased, can be a central issue for people bereaved by traffic accidents. This was revealed in an interview survey of recent Swedish roadside memorials and other memorial places. In this article we consider the design and selection of the memorial stone and gravesite as expressions of continuing care for the deceased and as a way to offer comfort to the bereaved. Materiality, representation and presence will be discussed as crucial parts of the link between the living and the dead. Communicative, spatial and physical values are important also in the professional's design of common public memorial places. Of specific interest for this text are two design practice-based terms, memory object and passage landscape, which may be used by landscape architects when designing memorial places, such as cemeteries and public monuments. Throughout this text, we argue that memorial places like these are capable of bridging the gap between the space of life and the space of death, as well as supporting the regeneration of present memories and the construction of future ones

First-principles Simulations of the stretching and final breaking of Al nanowires: Mechanical properties and electrical conductance

The evolution of the structure and conductance of an Al nanowire subject to a tensile stress has been studied by first-principles total-energy simulations. Our calculations show the correlation between discontinuous changes in the force (associated to changes in the bonding structure of the nanowire) and abrupt modifications of the conductance as the nanowire develops a thinner neck, in agreement with the experiments. We reproduce the characteristic increase of the conductance in the last plateau, reaching a value close to the conductance quantum $G_0 = 2 e^2 / h$ before the breaking of the nanowire. A dimer defines the contact geometry at these last stages, with three channels (one dominant) contributing to the conductance.Comment: 4 pages, 4 figure