Anatomical and experimental studies on the temporal pole of the macaque

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49953/1/900960203_ftp.pd

The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

An anatomical and experimental study of temporal and occipital association areas

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49951/1/900950306_ftp.pd

Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome

Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials

Interest representation in the EU: an open and structured dialogue?

Since 1992, the European Commission has sought to build ‘An Open and Structured Dialogue’ with interest groups, and since 2001 a broader ‘Dialogue with Civil Society’. A core feature of this dialogue involves instruments of transparency, and pluralism, with funding to ensure the presence of a wide range of voices. Consultation procedures provide for a ‘marketplace of ideas’ which simulate political competition and contestation, with a ‘voice but not a vote’, and which are supposed to provide for answerability by the European Commission for its policy choices. The European Commission also selects its allies to support its regulatory proposals, with NGOs frequent allies as well as firms and business sectors supporting higher standards. The EU’s fragmented decision-making system helps to provide a naturally pluralist environment, although some recent research suggests that NGOs are more likely to be successful in securing their policy goals than business organizations. NGOs work mostly in coalitions, with the size of coalition a factor in lobbying success. The saliency of issues is another substantial feature of variation in lobbying success and where NGOs can raise the contention of issues they can bring wider participation in EU issues

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Refining transcriptional programs in kidney development by integration of deep RNA-sequencing and array-based spatial profiling

<p>Abstract</p> <p>Background</p> <p>The developing mouse kidney is currently the best-characterized model of organogenesis at a transcriptional level. Detailed spatial maps have been generated for gene expression profiling combined with systematic <it>in situ </it>screening. These studies, however, fall short of capturing the transcriptional complexity arising from each locus due to the limited scope of microarray-based technology, which is largely based on "gene-centric" models.</p> <p>Results</p> <p>To address this, the polyadenylated RNA and microRNA transcriptomes of the 15.5 dpc mouse kidney were profiled using strand-specific RNA-sequencing (RNA-Seq) to a depth sufficient to complement spatial maps from pre-existing microarray datasets. The transcriptional complexity of RNAs arising from mouse RefSeq loci was catalogued; including 3568 alternatively spliced transcripts and 532 uncharacterized alternate 3' UTRs. Antisense expressions for 60% of RefSeq genes was also detected including uncharacterized non-coding transcripts overlapping kidney progenitor markers, Six2 and Sall1, and were validated by section <it>in situ </it>hybridization. Analysis of genes known to be involved in kidney development, particularly during mesenchymal-to-epithelial transition, showed an enrichment of non-coding antisense transcripts extended along protein-coding RNAs.</p> <p>Conclusion</p> <p>The resulting resource further refines the transcriptomic cartography of kidney organogenesis by integrating deep RNA sequencing data with locus-based information from previously published expression atlases. The added resolution of RNA-Seq has provided the basis for a transition from classical gene-centric models of kidney development towards more accurate and detailed "transcript-centric" representations, which highlights the extent of transcriptional complexity of genes that direct complex development events.</p

Virtual hallucinations: projects in VJing, virtual reality and cyberculture

This paper discusses a variety of the author’s artistic projects exploring altered states of consciousness and computer art. First, the paper will provide a brief overview of previous creative works, which include compositions of electroacoustic music, interactive visualisations, and visual music films. These previous works use the concept of altered states of consciousness as a compositional principle, as explored in the author’s book Inner Sound: Altered States of Consciousness in Electronic Music and Audio-Visual Media (OUP 2018). Following this, a variety of the author’s recent creative work produced from 2016–2019 will be discussed. These works include: a series of paintings that incorporate computer graphics animations when viewed in augmented reality; VJ performances constructed using direct animation on 8mm film, computer graphics animations generated from code and audio-reactive effects; and Cyberdream VR, a virtual reality experience. These interrelated projects continue to develop the author’s artistic investigations into altered states, while also referencing work such as demo scene videos; cyberdelic imagery of the type seen on fliers from the 1990s rave-era; and the recent Internet-borne subculture vaporwave, which recontextualises the aesthetics of 1980s and 1990s ambient corporate music and utopian computer graphics to construct surrealistic dystopias

What future, which technology? On the problem of describing relevant futures.

Doing research on future and emerging technologies raises a number of significant ontological and epistemological challenges. The fundamental uncertainty of the future, combined with problems of appropriate descriptions of technology in general, render it difficult to come to an appropriate account of the likely shape and use of future technologies. This paper discusses several streams of research that address this issue, including the question of relevant description and context, interpretive flexibility, affordances of technology, and multi-stability of technological trajectories. The paper proposes that some of these problems may be addressed by using a democratic and participative approach to technology research and development. Participative technology assessment is then discussed as an example of an established way of democratically engaging with technology stakeholders during research and development. The paper concludes by discussing the promises and limitations of such a participative approach with regard to the question of understanding and researching future technologies