Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits

Aesthetic Perspectives on Urban Technologies : Conceptualizing and Evaluating the Technology-Driven Changes in the Urban Everyday Experience

The pervasiveness of technology has undeniably changed the way the urban everyday is structured and experienced. Understanding the deep impact of this development on the everyday experience and its foundational aesthetic components is needed in order to determine how the skills and capacities to cope with the change, as well as to steer it, can be improved. Urban technology solutions – how they are defined, applied and used – are changing the sphere of everyday experience for urban dwellers. Philosophical and applied approaches to urban aesthetics offer perspectives to understand technologically mediated sensory experiences within the urban realm. This chapter shows how new urban technologies act as an agent of change within the familiar urban environment. We outline how the perspective of philosophical aesthetics can be used to understand urban technologies and their role in the constitution of everyday urban lifeworlds.The pervasiveness of technology has changed the way urban everyday is structured and experienced. An understanding of the deep impact of this development on everyday experience and its foundational aesthetic components is necessary in order to determine how skills and capacities can be improved in coping with such change, as well as managing it. Urban technology solutions – how they are defined, applied and used – are changing the sphere of everyday experience for urban dwellers. Philosophical and applied approaches to urban aesthetics offer perspectives on understanding technologically mediated sensory experiences within the urban realm. This chapter shows how new urban technologies act as an agent of change within the familiar urban environment. We outline how the perspective of philosophical aesthetics can be used to understand urban technologies and their role in the constitution of everyday urban lifeworlds.Peer reviewe

Determinants of impact : towards a better understanding of encounters with the arts

The article argues that current methods for assessing the impact of the arts are largely based on a fragmented and incomplete understanding of the cognitive, psychological and socio-cultural dynamics that govern the aesthetic experience. It postulates that a better grasp of the interaction between the individual and the work of art is the necessary foundation for a genuine understanding of how the arts can affect people. Through a critique of philosophical and empirical attempts to capture the main features of the aesthetic encounter, the article draws attention to the gaps in our current understanding of the responses to art. It proposes a classification and exploration of the factors—social, cultural and psychological—that contribute to shaping the aesthetic experience, thus determining the possibility of impact. The ‘determinants of impact’ identified are distinguished into three groups: those that are inherent to the individual who interacts with the artwork; those that are inherent to the artwork; and ‘environmental factors’, which are extrinsic to both the individual and the artwork. The article concludes that any meaningful attempt to assess the impact of the arts would need to take these ‘determinants of impact’ into account, in order to capture the multidimensional and subjective nature of the aesthetic experience

The Tourist Experience of Heritage Urban Spaces: Valletta as a Case Study

This article provides an understanding of how tourists experience heritage urban spaces by investigating features that influence tourist experiences most. It is framed within urban design literature which refers to three elements of urban space namely physical setting (or form), activity, and meaning. These elements are used to explore how urban spaces are experienced by tourists. Its findings are derived from an in-depth qualitative analysis of interviews with tourists to Valletta, Malta. The research suggests that the intrinsic qualities of the space are relevant to the tourist experience but what is even more relevant are the interactions of the tourist with different elements within that space, namely interactions with surroundings, interactions with others, and interactions with self/meaning. Within this broad conceptual model, the research identifies important sub-themes. Some of these reinforce the findings of existing work on tourist experiences, but others are often under-estimated or neglected

Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits

Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease

Cerebral small vessel disease-related brain lesions such as white matter lesions and lacunes are common findings of magnetic resonance imaging in the elderly. These lesions are thought to be major contributors to disability in old age, and risk factors that include age and hypertension have been established. The radiological, histopathologic and clinical phenotypes of age-related cerebral small vessel disease remarkably resemble autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, which is caused by mutations in NOTCH3. We hypothesized that genetic variations in NOTCH3 also play a role in age-related cerebral small vessel disease. We directly sequenced all 33 exons, the promoter and 3′-untranslated region of NOTCH3 in 195 participants with either coalescent white matter lesions or lacunes and compared the results to 82 randomly selected participants with no focal changes on magnetic resonance images in the Austrian Stroke Prevention Study. We detected nine common and 33 rare single nucleotide polymorphisms, of which 20 were novel. All common single nucleotide polymorphisms were genotyped in the entire cohort (n = 888), and four of them, rs1043994, rs10404382, rs10423702 and rs1043997, were associated significantly with both the presence and progression of white matter lesions. The association was confined to hypertensives, a result which we replicated in the Cohorts for Heart and Ageing Research in Genomic Epidemiology Consortium on an independent sample of 4773 stroke-free hypertensive elderly individuals of European descent (P = 0.04). The 33 rare single nucleotide polymorphisms were scattered over the NOTCH3 gene with three being located in the promoter region, 24 in exons (18 non-synonymous), three in introns and three in the 3′-untranslated region. None of the single nucleotide polymorphisms affected a cysteine residue. Sorting Intolerant From Tolerant, PolyPhen2 analyses and protein structure simulation consistently predicted six of the non-synonymous single nucleotide polymorphisms (H170R, P496L, V1183M, L1518M, D1823N and V1952M) to be functional, with four being exclusively or mainly detected in subjects with severe white matter lesions. In four individuals with rare non-synonymous single nucleotide polymorphisms, we noted anterior temporal lobe hyperintensity, hyperintensity in the external capsule, lacunar infarcts or subcortical lacunar lesions. None of the observed abnormalities were specific to cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. This is the first comprehensive study investigating (i) the frequency of NOTCH3 variations in community-dwelling elderly and (ii) their effect on cerebral small vessel disease related magnetic resonance imaging phenotypes. We show that the NOTCH3 gene is highly variable with both common and rare single nucleotide polymorphisms spreading across the gene, and that common variants at the NOTCH3 gene increase the risk of age-related white matter lesions in hypertensives. Additional investigations are required to explore the biological mechanisms underlying the observed association