Comparative survey of the relative impact of mRNA features on local ribosome profiling read density

Ribosome profiling (Ribo-seq), a promising technology for exploring ribosome decoding rates, is characterized by the presence of infrequent high peaks in ribosome footprint density and by long alignment gaps. Here, to reduce the impact of data heterogeneity we introduce a simple normalization method, Ribo-seq Unit Step Transformation (RUST). RUST is robust and outperforms other normalization techniques in the presence of heterogeneous noise. We illustrate how RUST can be used for identifying mRNA sequence features that affect ribosome footprint densities globally. We show that a few parameters extracted with RUST are sufficient for predicting experimental densities with high accuracy. Importantly the application of RUST to 30 publicly available Ribo-seq data sets revealed a substantial variation in sequence determinants of ribosome footprint frequencies, questioning the reliability of Ribo-seq as an accurate representation of local ribosome densities without prior quality control. This emphasizes our incomplete understanding of how protocol parameters affect ribosome footprint densities.

The conformational landscape of RNA translational regulators and their potential as drug discovery targets

RNA is an underutilized target for drug discovery. Once thought to be a passive carrier of genetic information, RNA is now known to play a critical role in essentially all aspects of biology including signaling, gene regulation, catalysis, and retroviral infection. It is now well-established that RNA does not exist as a single static structure, but instead populates an ensemble of energetic minima along a free-energy landscape. Knowledge of this structural landscape has become an important goal for understanding its diverse biological functions. In this case, NMR spectroscopy has emerged as an important player in the characterization of RNA structural ensembles, with solution-state techniques accounting for almost half of deposited RNA structures in the PDB, yet the rate of RNA structure publication has been stagnant over the past decade. Several bottlenecks limit the pace of RNA structure determination by NMR: the high cost of isotopic labeling, tedious and ambiguous resonance assignment methods, and a limited database of RNA optimized pulse programs. We have addressed some of these challenges to NMR characterization of RNA structure with applications to various RNA-drug targets. These approaches will increasingly become integral to designing new therapeutics targeting RNA.

Energy landscape view of phase transitions and slow dynamics in thermotropic liquid crystals

Thermotropic liquid crystals are known to display rich phase behavior on temperature variation. Although the nematic phase is orientationally ordered but translationally disordered, a smectic phase is characterized by the appearance of a partial translational order in addition to a further increase in orientational order. In an attempt to understand the interplay between orientational and translational order in the mesophases that thermotropic liquid crystals typically exhibit upon cooling from the high-temperature isotropic phase, we investigate the potential energy landscapes of a family of model liquid crystalline systems. The configurations of the system corresponding to the local potential energy minima, known as the inherent structures, are determined from computer simulations across the mesophases. We find that the depth of the potential energy minima explored by the system along an isochor grows through the nematic phase as temperature drops in contrast to its insensitivity to temperature in the isotropic and smectic phases. The onset of the growth of the orientational order in the parent phase is found to induce a translational order, resulting in a smectic-like layer in the underlying inherent structures; the inherent structures, surprisingly, never seem to sustain orientational order alone if the parent nematic phase is sandwiched between the high-temperature isotropic phase and the low-temperature smectic phase. The Arrhenius temperature dependence of the orientational relaxation time breaks down near the isotropic-nematic transition. We find that this breakdown occurs at a temperature below which the system explores increasingly deeper potential energy minima.

Capturing Australian indigenous perception of virtual landscape

This short paper presents a means of capturing non spatial information (specifically understanding of places) for use in a Virtual Heritage application. This research is part of the Digital Songlines Project which is developing protocols, methodologies and a toolkit to facilitate the collection and sharing of Indigenous cultural heritage knowledge, using virtual reality. Within the context of this project most of the cultural activities relate to celebrating life and to the Australian Aboriginal people, land is the heart of life. Australian Indigenous art, stories, dances, songs and rituals celebrate country as its focus or basis. To the Aboriginal people the term “Country” means a lot more than a place or a nation, rather “Country” is a living entity with a past a present and a future; they talk about it in the same way as they talk about their mother. The landscape is seen to have a spiritual connection in a view seldom understood by non-indigenous persons; this paper introduces an attempt to understand such empathy and relationship and to reproduce it in a virtual environment.

Landscape symphonies : gardening as a source of landscape architecture practice engaged with change

The notion of designing with change constitutes a fundamental and foundational theoretical premise for much of what constitutes landscape architecture, notably through engagement with ecology, particularly since the work of Ian McHarg in the 1960s and his key text Design with Nature. However, while most if not all texts in landscape architecture would cite this engagement of change theoretically, few go any further than citation, and when they do their methods seem fixated on utilising empirical, quantitative scientific tools for doing so, rather than the tools of design, in an architectural sense, as implied by the name of the discipline, landscape architecture.

Concerning the house museum and the picturesque landscape in the work of Sir John Soane : with raw hints for post-heritage museum space

The picturesque aesthetic in the work of Sir John Soane, architect and collector, resonates in the major work of his very personal practice – the development of his house museum, now the Soane Museum in Lincoln’s Inn Fields in London. Soane was actively involved with the debates, practices and proponents of picturesque and classical practices in architecture and landscape and his lectures reveal these influences in the making of The Soane, which was built to contain and present diverse collections of classical and contemporary art and architecture alongside scavenged curiosities. The Soane Museum has been described as a picturesque landscape, where a pictorial style, together with a carefully defined itinerary, has resulted in the ‘apotheosis of the Picturesque interior’. Soane also experimented with making mock ruinscapes within gardens, which led him to construct faux architectures alluding to archaeological practices based upon the ruin and the fragment. These ideas framed the making of interior landscapes expressed through spatial juxtapositions of room and corridor furnished with the collected object that characterise The Soane Museum. This paper is a personal journey through the Museum which describes and then reviews aspects of Soane’s work in the context of contemporary theories on ‘new’ museology. It describes the underpinning picturesque practices that Soane employed to exceed the boundaries between interior and exterior landscapes and the collection. It then applies particular picturesque principles drawn from visiting The Soane to a speculative project for a house/landscape museum for the Oratunga historic property in outback South Australia, where the often, normalising effects of conservation practices are reviewed using minimal architectural intervention through a celebration of ruinous states.

The MESH book : landscape / infrastructure

Resulting from a series of student-run 'Edge' conferences that have been held in Australia and New Zealand (beginning at RMIT in 1983), The Mesh Book is a collection of essays grouped into themes of Invisible Infrastructures (systems of belief), Immanent Infrastructures (natural systems) and Present Infrastructures (roads and services). Ranging from esoteric discussions to analytical case studies, the book assembles a broad spectrum of ideas on the landscape within the context of Australia and a contemporary study of place.

Landscape landscapism

Clearly the world is a different place to what it was 40 years ago, and much of that difference can be characterised as disturbances to the local on the basis of globalism, particularly due to changes in communication and information technology. Like it did to modernism before it, this societal change calls for, or more aptly calls to, designers to reformulate their practices to reflect this significant new paradigm. This is a rationale that has driven much avant-garde activity in the 20th century, and in this case, 'landscape urbanism' in the 21st. In the case of this discussion, it is important to recognise the avant-garde cycle at work in the development of the discipline, not only to contextualise its production, but so that its greatest values can be welcomed: despite the propaganda and arrogance, important revisions occurred to the canons after all the -isms. That said, I do find myself asking: do we need another -ism?

Modern landscape

Landscape is a perennial source of conceptual material for most creative disciplines, and, arguably, everything else, but it is always irritating to landscape architects how it is seized on by architects when their own canon is boring them or their language of form is getting a bit straight. What is frustrating is that while landscape architecture attempts to come to terms with factors, systems and nuances of situations that may result in form, there is a tendency in architecture to make icons of generic 'natural' archetypes. This is not to say that landscape architecture has yet developed a strong formal language that engages with these nuances, just that the struggle with them is at its root, and this struggle with specificity in the face of generic-ness is a noble one. In the face of this, to see architecture describe a 'new' and 'innovative' interest in landscape in 'the ground' seems like a diversion: surely there must be innovation in a real, articulate and sophisticated understanding of the architectural canon.

Real Design of a Virtual Landscape : Designing and building a landscape in Second Life

3D Virtual Environments (VE) are real; they exist as digital worlds with the advantage of having none of the constraints of the real world. As such they are the perfect training ground for design students who can create, build and experiment with design solutions without the constraint of real world projects. This paper reports on an educational setting used to explore a model for using VE such as Second Life (SL) developed by Linden Labs in California, as a collaborative environment for design education. A postgraduate landscape architecture learning environment within a collaborative design unit was developed to integrate this model where the primary focus was the application of three-dimensional tools within design, not as a presentation tool, but rather as a design tool. The focus of the unit and its aims and objectives will be outlined before describing the use of SL in the unit. Attention is focused on the collaboration and learning experience before discussing the outcomes, student feedback, future projects using this model and potential for further research. The outcome of this study aims to contribute to current research on teaching and learning design in interactive VE’s. We present a case study of our first application of this model.