John Locke and the fable of liberalism

This article explores the ways in which John Locke was claimed by liberalism and refashioned in its image. It was Locke's fate to become the hero of what I term 'the fable of liberalism', the story liberalism recounts to itself about its origins and purposes. Locke is a pivotal figure - perhaps the pivotal figure - in this stony, because he put into currency conceptions which contributed centrally to the emergence and spread of liberal ways of thinking about politics which continue to ramify. It was Locke who established that the legitimacy of a political authority was a necessary condition of obedience to it and that its legitimacy was a product of the consensual route by which it came into existence; it was Locke who established that the route by which it came into existence determined the ends for which it existed and, with these, the scope of its authority. All this was explained in an exemplary way by Locke (the story goes), and he remains the great exemplar for understanding and conducting politics legitimately even today. This article puts question marks beside the Locke who emerges from this story. It substitutes a new and very different Locke in his place

Popular sovereignty in an age of mass democracy : politics, parliament and parties in Weber, Kelsen, Schmitt and beyond

Max Weber developed a distinctive view of the possibilities and polarities of modern politics. His thinking about popular sovereignty is placed in the context of a long-running German debate about how to reconcile two principles, those of popular self-government from below and authority from above. Weber’s unwillingness to compromise these principles, or to subordinate one to the other, led him to adopt different positions at different times about the role of parliament and political parties in holding these two principles together in practice. As a result, he bequeathed no single set of bearings to the future. An attempt is made to show, by means of an analysis of the ways in which Weber developed his positions, and by a comparison of those positions with views developed in response by Hans Kelsen and Carl Schmitt, that the question of whether Weber’s thought led directly to Schmitt’s or, indeed, to Kelsen’s, is a question mal posée. What popular sovereignty means in an age of mass democracy remains an open question which we must answer for ourselves

Maximizing Sharability and Persuasiveness on Web 2.0

Online marketing efforts usually focus on the persuasiveness or sharability of a message. However, research has not established where these two concepts overlap. The current study explores this overlap. Web 2.0 platforms facilitate the delivery of different content and statistics to convey the persuasiveness and the sharability. An original experiment varied message quality (high argument strength, direct message, and emotional message) and web cues (i.e., ratio of views, likes, and shares) to signal self-presentation (favorable and unfavorable). Prospective participants will view mock webpages for internet news and donation collection, followed by measures of the content persuasiveness and sharability

Protein Design with Guided Discrete Diffusion

A popular approach to protein design is to combine a generative model with a discriminative model for conditional sampling. The generative model samples plausible sequences while the discriminative model guides a search for sequences with high fitness. Given its broad success in conditional sampling, classifier-guided diffusion modeling is a promising foundation for protein design, leading many to develop guided diffusion models for structure with inverse folding to recover sequences. In this work, we propose diffusioN Optimized Sampling (NOS), a guidance method for discrete diffusion models that follows gradients in the hidden states of the denoising network. NOS makes it possible to perform design directly in sequence space, circumventing significant limitations of structure-based methods, including scarce data and challenging inverse design. Moreover, we use NOS to generalize LaMBO, a Bayesian optimization procedure for sequence design that facilitates multiple objectives and edit-based constraints. The resulting method, LaMBO-2, enables discrete diffusions and stronger performance with limited edits through a novel application of saliency maps. We apply LaMBO-2 to a real-world protein design task, optimizing antibodies for higher expression yield and binding affinity to several therapeutic targets under locality and developability constraints, attaining a 99% expression rate and 40% binding rate in exploratory in vitro experiments

XThe psychosocial impact of living with an ocular prosthesis

Objective: Many patients are satisfied with their ocular prosthesis, but some describe problems with social interactions, body image and self-esteem. Although both clinical practice and research suggest that the severity of a disfiguring condition does not predict distress, there has been little research with patients living with an ocular prosthesis. The objective was to explore the psychological impact of living with an artificial eye or cosmetic shell and determine the relationship between psychological well-being and clinical and psychosocial factors. Methods: A cross-sectional study between March and September 2008 at the ocular prosthesis clinic of Moorfields Eye Hospital, UK. The primary outcome measures were mood as measured by the Hospital Anxiety and Depression Scale (HADS) and appearance-related social anxiety and social avoidance, as measured by the Derriford Appearance Scale (DAS24). Results: Mean scores on the HADS and DAS24 were within normal range, but a considerable proportion of participants were experiencing significant levels of distress. Psychosocial adjustment was unrelated to most clinical and demographic variables, but was associated with a series of cognitive processes. Conclusions: Psychological variables, rather than clinical or demographic factors, are associated with how a patient adjusts to wearing an ocular prosthesis. Such factors might be amenable to change through psychosocial intervention

My neighbourhood: Studying perceptions of urban space and neighbourhood with moblogging

We describe a novel methodology that examines perceptions of urban space, and present a study using this methodology that explores people’s perceptions of their neighbourhood. Previous studies of spatial cues have involved a variety of tasks such as pointing and sketching to externalise participants’ internal spatial maps. Our methodology extends these approaches by introducing mobile technologies alongside traditional materials and tasks. Participants use mobile phones to carry out self-guided neighbourhood tours. We collected rich qualitative data from 15 participants during two workshops and a self-directed neighbourhood tour. Our study highlights the use of public and private landmarks, differences in spatial maps of rural versus urban dwellers, and individual variance in orientation strategies. These themes suggest guidelines for the design of technologies with personalised spatial profiles

Salience and valence of appearance in a population with a visible difference of appearance: Direct and moderated relationships with self-consciousness, anxiety and depression

Psychometric measures of appearance salience and valence, CARSAL and CARVAL, have been previously demonstrated to be key factors underpinning appearance related self-consciousness and negative affect in the general population. However, the extent to which the scales are appropriate for people with a visibly different appearance has not previously been reported. Neither has the moderating effect of appearance salience (CARSAL) on the relationship between appearance valence (CARVAL) and appearance self-consciousness, previously shown in a general population sample, been replicated with people who are visibly different. Twelve hundred and sixty five participants with a visible difference in either secondary care (n = 651) or the community (n = 614) provided data. Analysis confirmed the psychometric qualities of both CARSAL and CARVAL, and the conceptual independence of each scale. The scales also demonstrated independent and interdependent relationships with social anxiety and avoidance in relation to appearance, depression and anxiety. Appearance salience moderated the relationship with valence on these psychosocial measures. In summary, this paper corroborates the use of CARSAL and CARVAL with both visibly different and general adult populations for the measurement of appearance salience and valence. © 2014 Moss et al

BIG regulates dynamic adjustment of circadian period in Arabidopsis thaliana

Circadian clocks drive rhythms with a period near 24 h, though the molecular basis of the regulation of circadian period is little understood. We have demonstrated previously that metabolites affect the free-running period of the circadian oscillator of Arabidopsis thaliana, with endogenous sugars acting as an accelerator and exogenous nicotinamide acting as a brake. Changes in circadian oscillator period are thought to adjust the timing of biological activities through the process of entrainment, in which the circadian oscillator becomes synchronised to rhythmic signals such as light and dark cycles, and changes in internal metabolism. To identify molecular components associated with the dynamic adjustment of circadian period we performed a forward genetic screen. We identified mutants that were either period insensitive to nicotinamide (sin) or period oversensitive to nicotinamide (son). We mapped son1 to BIG, a gene of unknown molecular function that has previously been reported to have a role in light signalling. We found that son1 has an early entrained phase suggesting that the dynamic alteration of circadian period contributes to the correct timing of biological events. Our data provide an insight in to how dynamic period adjustment of circadian oscillators contributes to establishing a correct phase relationship with the environment and identifies that BIG is involved in this process

Automated Analysis of Flow Cytometry Data to Reduce Inter-Lab Variation in the Detection of Major Histocompatibility Complex Multimer-Binding T Cells

Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual labs. Therefore, strategies to provide automated analysis of major histocompatibility complex (MHC) multimer-binding T cells represent an attractive solution to decrease subjectivity and technical variation. The challenge of using an automated analysis approach is that MHC multimer-binding T cell populations are often rare and therefore difficult to detect. We used a highly heterogeneous dataset from a recent MHC multimer proficiency panel to assess if MHC multimer-binding CD8+ T cells could be analyzed with computational solutions currently available, and if such analyses would reduce the technical variation across different laboratories. We used three different methods, FLOw Clustering without K (FLOCK), Scalable Weighted Iterative Flow-clustering Technique (SWIFT), and ReFlow to analyze flow cytometry data files from 28 laboratories. Each laboratory screened for antigen-responsive T cell populations with frequency ranging from 0.01 to 1.5% of lymphocytes within samples from two donors. Experience from this analysis shows that all three programs can be used for the identification of high to intermediate frequency of MHC multimer-binding T cell populations, with results very similar to that of manual gating. For the less frequent populations (<0.1% of live, single lymphocytes), SWIFT outperformed the other tools. As used in this study, none of the algorithms offered a completely automated pipeline for identification of MHC multimer populations, as varying degrees of human interventions were needed to complete the analysis. In this study, we demonstrate the feasibility of using automated analysis pipelines for assessing and identifying even rare populations of antigen-responsive T cells and discuss the main properties, differences, and advantages of the different methods tested