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Royal Holloway, University of London
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Royal Holloway, University of London | Date: 2017-03-22

Molecules are provided for inducing or facilitating exon skipping in forming spliced mRNA products from pre-mRNA molecules in cells. The molecules may be provided directly as oligonucleotides or expression products of vectors that are administered to a subject. High rates of skipping can be achieved. High rates of skipping reduce the severity of a disease like Duchene Muscular Dystrophy so that the disease is more like Becker Muscular Dystrophy. This is a severe reduction in symptom severity and mortality.

Eschrig M.,Royal Holloway, University of London
Reports on Progress in Physics | Year: 2015

During the past 15 years a new field has emerged, which combines superconductivity and spintronics, with the goal to pave a way for new types of devices for applications combining the virtues of both by offering the possibility of long-range spin-polarized supercurrents. Such supercurrents constitute a fruitful basis for the study of fundamental physics as they combine macroscopic quantum coherence with microscopic exchange interactions, spin selectivity, and spin transport. This report follows recent developments in the controlled creation of long-range equalspin triplet supercurrents in ferromagnets and its contribution to spintronics. The mutual proximityinduced modification of order in superconductor-ferromagnet hybrid structures introduces in a natural way such evasive phenomena as triplet superconductivity, odd-frequency pairing, FuldeFerrellLarkinOvchinnikov pairing, long-range equal-spin supercurrents, π-Josephson junctions, as well as long-range magnetic proximity effects. All these effects were rather exotic before 2000, when improvements in nanofabrication and materials control allowed for a new quality of hybrid structures. Guided by pioneering theoretical studies, experimental progress evolved rapidly, and since 2010 triplet supercurrents are routinely produced and observed. We have entered a new stage of studying new phases of matter previously out of our reach, and of merging the hitherto disparate fields of superconductivity and spintronics to a new research direction: super-spintronics. © 2015 IOP Publishing Ltd.

Davis C.J.,Royal Holloway, University of London
Psychological Review | Year: 2010

Visual word identification requires readers to code the identity and order of the letters in a word and match this code against previously learned codes. Current models of this lexical matching process posit context-specific letter codes in which letter representations are tied to either specific serial positions or specific local contexts (e.g., letter clusters). The spatial coding model described here adopts a different approach to letter position coding and lexical matching based on context-independent letter representations. In this model, letter position is coded dynamically, with a scheme called spatial coding. Lexical matching is achieved via a method called superposition matching, in which input codes and learned codes are matched on the basis of the relative positions of their common letters. Simulations of the model illustrate its ability to explain a broad range of results from the masked form priming literature, as well as to capture benchmark findings from the unprimed lexical decision task. © 2010 American Psychological Association.

Hall R.,Royal Holloway, University of London
Tectonophysics | Year: 2012

The heterogeneous Sundaland region was assembled by closure of Tethyan oceans and addition of continental fragments. Its Mesozoic and Cenozoic history is illustrated by a new plate tectonic reconstruction. A continental block (Luconia-Dangerous Grounds) rifted from east Asia was added to eastern Sundaland north of Borneo in the Cretaceous. Continental blocks that originated in western Australia from the Late Jurassic are now in Borneo, Java and Sulawesi. West Burma was not rifted from western Australia in the Jurassic. The Banda (SW Borneo) and Argo (East Java-West Sulawesi) blocks separated from western Australia and collided with the SE Asian margin between 110 and 90. Ma, and at 90. Ma the Woyla intra-oceanic arc collided with the Sumatra margin. Subduction beneath Sundaland terminated at this time. A marked change in deep mantle structure at about 110°E reflects different subduction histories north of India and Australia since 90. Ma. India and Australia were separated by a transform boundary that was leaky from 90 to 75. Ma and slightly convergent from 75 to 55. Ma. From 80. Ma, India moved rapidly north with north-directed subduction within Tethys and at the Asian margin. It collided with an intra-oceanic arc at about 55. Ma, west of Sumatra, and continued north to collide with Asia in the Eocene. Between 90 and 45. Ma Australia remained close to Antarctica and there was no significant subduction beneath Sumatra and Java. During this interval Sundaland was largely surrounded by inactive margins with some strike-slip deformation and extension, except for subduction beneath Sumba-West Sulawesi between 63 and 50. Ma. At 45. Ma Australia began to move north; subduction resumed beneath Indonesia and has continued to the present. There was never an active or recently active ridge subducted in the Late Cretaceous or Cenozoic beneath Sumatra and Java. The slab subducted between Sumatra and east Indonesia in the Cenozoic was Cretaceous or older, except at the very western end of the Sunda Arc where Cenozoic lithosphere has been subducted in the last 20. million years. Cenozoic deformation of the region was influenced by the deep structure of Australian fragments added to the Sundaland core, the shape of the Australian margin formed during Jurassic rifting, and the age of now-subducted ocean lithosphere within the Australian margin. © 2012 Robert Hall.

Norbury C.F.,Royal Holloway, University of London
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2014

Background DSM-5 sees the introduction of Social (Pragmatic) Communication Disorder (SPCD), characterized by persistent difficulties using verbal and nonverbal communication for social purposes, in the absence of restricted and repetitive interests and behaviours. There is currently much confusion about the precise diagnostic criteria for SPCD and how this disorder relates to autism spectrum disorders (ASD), previous descriptions of pragmatic language impairment (PLI) and more specific language disorders (LD). Method Proposed criteria for SPCD are outlined. A selective review of the evidence considers whether these criteria form a cohesive and distinct diagnostic entity. Approaches to assessment and intervention are discussed. Results Implementing the new diagnosis is currently challenged by a lack of well-validated and reliable assessment measures, and observed continuities between SPCD and other neurodevelopmental disorders. High rates of comorbidity between SPCD and other seemingly disparate disorders (including conduct disorder, ADHD and disorders of known genetic origin) raise questions about the utility of this diagnostic category. Conclusions SPCD is probably best conceptualized as a dimensional symptom profile that may be present across a range of neurodevelopmental disorders, although there is an urgent need to investigate the latent structure of SPCD using consistent diagnostic criteria. In addition, social communication and aspects of pragmatic language may be dissociated, with the latter heavily influenced by structural language attainments. Finally, there is a dearth of reliable and culturally valid assessment measures with which to make a differential diagnosis, and few rigorously tested intervention programmes. The implications for research and clinical practice are outlined. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Jarvis P.,University of Oxford | Lopez-Juez E.,Royal Holloway, University of London
Nature Reviews Molecular Cell Biology | Year: 2013

Chloroplasts are the organelles that define plants, and they are responsible for photosynthesis as well as numerous other functions. They are the ancestral members of a family of organelles known as plastids. Plastids are remarkably dynamic, existing in strikingly different forms that interconvert in response to developmental or environmental cues. The genetic system of this organelle and its coordination with the nucleocytosolic system, the import and routing of nucleus-encoded proteins, as well as organellar division all contribute to the biogenesis and homeostasis of plastids. They are controlled by the ubiquitin-proteasome system, which is part of a network of regulatory mechanisms that integrate plastid development into broader programmes of cellular and organismal development. © 2013 Macmillan Publishers Limited. All rights reserved.

Agency: GTR | Branch: NERC | Program: | Phase: Research Grant | Award Amount: 156.18K | Year: 2017

The Earths mantle forms almost all of the Earths volume, and is thought to be made of material similar to stony meteorites. Almost everywhere on Earth it lies beneath a thin layer of crust that is the product of repeated mantle melting and remelting. Since the 1950s, drilling a MoHole through Earths crust to obtain the first in-place sample of its mantle has been a goal for Earth scientists comparable to obtaining samples from the Moon, Mars, or Venus. These samples are the only way to confirm or disprove many decades of work on how Earths oceanic and continental crust form and evolve, the geological processes that create volcanoes, Plate Tectonics, and the preconditions for Life on Earth. Continental crust is usually thicker than 30km, putting the mantle out of reach. The crust beneath the oceans, which covers 65% of the Earths surface, is often as thin as 5.5km and the task is now possible. This goal is achievable at a cost similar to a moderate space mission but requires an international community effort, and the Japanese have designed and built a £1000M drillship, the Chikyu, with the MoHole as a key objective. Offshore Central America is an especially promising site for the MoHole because the water depths of less than 4km and the plate age around 20Myr reduce the technical challenges, and the ocean crust formed at a well-studied fast (10cm/yr) mid-ocean spreading centre. In addition, this is the worlds only region where we can augment MoHole drilling to explore changes to the crust and mantle when a tectonic plate bends to subduct into Earths interior at an oceanic trench. Offshore Central America is the only place where this plate bending occurs shallower than the 4.5km seafloor-depth limit to Chikyu drilling operations. We now realize that plate bending near a trench is likely to be associated with significant chemical reactions between seawater and mantle just below the oceanic crust that has cooled significantly since it rose and melted beneatha mid-ocean ridge. Bend-faults formed just outboard of the trench appear to be key in this process, providing pathways for seawater through the crust and into the shallow mantle. Acoustic (seismic) tools developed for oil-exploration show these faults in the bending crust and up to 10km into the mantle in several places. We know from reduced seismic wavespeeds that seawater and cold mantle have reacted to form large amounts of a water-rich product called serpentine. If large amounts of serpentine are formed during plate bending, this would have profound implications for the Earths global carbon and water cycles. Carbonate formed as a serpentinization reaction product could transfer an amount of carbon dioxide into the mantle comparable to that consumed by surface weathering and mountain building. Deep chemosynthetic life is also likely to take advantage of the energy released by serpentinization reactions. This region may be where life penetrates most deeply into Earth and may even be the environment where life started. To test these ideas requires drilling through the crust and into the shallow mantle near one of these bend faults to sample the rocks and fluids. In this study we will test whether the plate offshore Central America is suitable for these two deep drilling projects. We will measure the crustal thickness, and the properties of the crust and upper mantle using seismic methods. We will determine where bend-faults form, how they evolve, and how the properties of the crust and mantle change as they do. We will specifically search for sites along a bend-fault where hot water returns to the seafloor after passing deep within the region of active serpentinization by mapping the seabed with an advanced robot submarine called Autosub and measuring the temperature of rocks 5m beneath the seabed. To find these sites and any lifeforms present would on its own be a major jump in our basic knowledge of the Earth.

Agency: GTR | Branch: EPSRC | Program: | Phase: Training Grant | Award Amount: 3.45M | Year: 2016

Royal Holloway has been producing PhDs in cyber security and related areas for over 30 years, the last 20 of which have been under the auspices of the Information Security Group. Since 2013, RHUL has hosted one of the EPSRC Centres for Doctoral Training in Cyber Security, with 30 students currently enrolled. In the three years since its establishment, the CDT has made a sustained and successful effort to recruit a strong cohort of students from a diverse range of backgrounds. It has given those students a broad grounding in cyber security in preparation for research and accelerated them into the phase of formal PhD research studies. We have established effective governance structures that ensure the smooth day-to-day running of the CDT without losing sight of long-term strategic objectives. We have engaged with business to enhance the training programme and to shape the CDT research portfolio. Research outputs from CDT students are frequently featured in top research conferences, with some specifically identified impacts in the real world. Feedback from our external partners in industry and government demonstrates the great value of the CDT to them. The strategic objectives of our CDT in Cyber Security are: to promote research in cyber security that is original, significant, and of international excellence; to encourage cyber security research that is responsive to the needs of society, both nationally and globally, particularly with regard to interdisciplinary working; to develop a cohort of researchers with a broad understanding of cyber security and an appreciation of the increasingly important interplay between theoretical, technical and human factors, as well as research skills; to seek new and develop existing relationships with the cyber security industry, in order to cultivate PhD graduates with the right skills to address the UKs future cyber security challenges; to engage with stakeholders in the cyber security industry, and society at large, in order to promote the work of the CDT and to inform the future research agenda; and to establish a doctoral training environment that will continue to meet the other strategic objectives beyond the lifetime of the funded CDT. In its new phase, our CDT in Cyber Security will recruit three further annual cohorts, starting in September 2016. Royal Holloway remains the best place to host one of the CDTs in Cyber Security, given our track record, our capacity, organisation and culture, and our close relationships with the cyber security industry. The CDT has not only greatly enhanced the research environment and business engagement at the university, but also cultivated students who truly have the potential to become leaders in their fields.

Agency: GTR | Branch: ESRC | Program: | Phase: Research Grant | Award Amount: 532.06K | Year: 2017

One remarkable aspect of human learning is our ability to build general knowledge from individual experiences. This general knowledge is central to virtually all cognitive functions, but is particularly important in language, as it allows us to use new words, phrases, and sentences that have not been communicated previously. For example, we understand the novel word untweetable because we have general knowledge of the functions of affixes {un} and {able}. However, despite the significance of this form of knowledge for human communication, we know remarkably little about how it is acquired. Recent research provides strong clues that sleep may play a vital role in the acquisition of general linguistic knowledge. In a previous ESRC project, we developed a laboratory analogue of language learning to track how general knowledge is built through multiple experiences with individual words. This research demonstrated that although new memories for individual items can be acquired rapidly, the process of discovering regularities across individual items to permit generalisation requires a period of overnight memory consolidation. The aim of the present research project is to discover whether sleep is the critical factor in the acquisition of general linguistic knowledge, and further, to describe the neural processes arising during sleep that facilitate this form of learning. This proposal describes three work packages that combine methods at the leading edge of sleep science with our laboratory analogue of language learning to uncover how sleep impacts on the development of item-specific and general knowledge. In the first work package, we track the acquisition of item-specific and general knowledge when there is a delay between training and testing, and assess whether it matters if that delay consists of overnight sleep as opposed to daytime wake. In the second work package, we investigate how sleep deprivation before or after training impacts on the acquisition of item-specific and general linguistic knowledge. In the third work package, we use an olfactory cuing technique to reactivate memories of newly-learned information during sleep, and measure whether this reactivation enhances the acquisition of linguistic knowledge. We then take this experimental paradigm one step further to ask whether we can bias the course of long-term learning by selectively reactivating particular memories. In all experiments involving sleep, we use polysomnography to assess the importance of particular sleep stages or neural events during sleep for different forms of learning. We also assess learning in all experiments after one week to draw conclusions about the stability of new knowledge over the longer term. International research has shown that the UK has one of the largest proportions of children who are sleep deprived, and that more than a quarter of the UK population gets on average less than five hours of sleep nightly. Given these statistics, it is of vital importance to understand what the consequences of poor sleep are for learning and memory. This research programme will address profound questions about how the brain continues to process new memories during sleep, how these sleep-related neural mechanisms shape the acquisition of long-term linguistic knowledge, and how sleep prepares the brain for new learning. Our findings will be transformative for theoretical models of learning, particularly as these apply to language, and will provide a range of new opportunities for creating substantive impacts within educational settings. We have developed a full programme of engagement with academic and non-academic stakeholders to realise this potential.

Agency: GTR | Branch: EPSRC | Program: | Phase: Research Grant | Award Amount: 2.71M | Year: 2016

Superconducting Quantum Technology (SuQT) is regarded across the world as one of the key technologies for the possible construction of a quantum computer. Based on fabrication techniques used in semi-conductor processing, the creation of electrical circuits that operate according to the laws of quantum physics is astonishing in that the devices are the first man made objects (as opposed to natural entities such as atoms, electrons and photons) to display quantum effects. They are all the more fantastic because of their ability to be modified by design or construction in ways that naturally quantum objects cannot. As quantum electrical (qubit) circuits, they hold the potential to solve all of the problems of addressability, controllability, controlled qubit coupling and readout that many other architectures based on natural quantum objects find difficult. This is the reason that major corporations such as Google, IBM and Raytheon are now beginning to provide market pull in providing funds to progress this field. Superconducting quantum devices pave the way not only for the development of quantum computing and fast algorithms for searching, information security and quantum simulation, but also open the door to a huge array of possible new sensing elements including those based on artificial atoms and quantum optics, but with microwaves, where the multi billion dollar communication industry operates. In order to enable the study and development of this new field we request funds for a state-of-the-art electron beam lithography (EBL) system that will enable the exploration and exploitation of a new generation of SuQT including quantum meta-materials, coherent quantum phase slip (with consequent potential for a redefinition of the unit of electrical current, the Ampere), microwave quantum optics and quantum limited amplification as well as further development of multi-qubit devices. As world leaders in the field we will build on our strong collaboration with the National Physical Laboratory and initiate a further collaboration with JEOL, the world-market leaders in EBL systems to form a consortium that can offer SuQT nanofabrication facilities to UK academia free of access charges for at least five years. We will collaborate strongly with another world leader in SuQT, Prof Yuri Pashkin (Lancaster University). We were the first group in the UK to successfully establish a superconducting qubit foundry, we will build on our state-of-the-art capability, supported by an approximately £20M investment by Royal Holloway in a new Department of Electronic Engineering, for which the EBL will underpin future research and providing a streamlined route from science to technology. Our aim is to establish the UK as a world leader in superconducting quantum technology.

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