Bioconjugation of Green Fluorescent Protein via an Unexpectedly Stable Cyclic Sulfonium Intermediate

Bioconjugation of superfolder GFP involving the formation of an unusually stable, and unprecedented, cyclic sulfonium species is described. This sulfonium can undergo smooth reaction with a range of nucleophiles to give sulfur-, selenium- and azide-modified GFP derivatives in high conversions

Nanosecond time transfer via shuttle laser ranging experiment

A method is described to use a proposed shuttle laser ranging experiment to transfer time with nanosecond precision. All that need be added to the original experiment are low cost ground stations and an atomic clock on the shuttle. It is shown that global time transfer can be accomplished with 1 ns precision and transfer up to distances of 2000 km can be accomplished with better than 100 ps precision

Looking for concepts in Early Modern English

The idea that conceptual meaning in discourse could be identified in constellations of lexical co-occurrences in a particular “universe” of discourse was key in guiding the computational historical semantic–pragmatic work conducted in the Linguistic DNA project. The project mapped prominent lexical co-occurrences across the two hundred years of publications in Early English Books Online (EEBO-TCP; Text Creation Partnership edition), yielding concept models – constellations of non-adjacent lemmas that consistently co-occur across spans of up to 100 tokens. The goal was to map meaning onto concept models as “discursive concepts”, using encyclopaedic knowledge, pragmatic analysis and context. The first question concerns the effectiveness of making early hypotheses about the discursive meaning of concept models based on the inferred connections between the lemmas in a quad constellation. The second question is whether the meaning of frequent, apparently stable concept models changes upon their closer scrutiny in the discourses they lead us into. A reader familiar with the particular universe of discourse in which these quads occur, and with the social, historical, literary and philosophical traditions, and the context that they occupy, might be effectively primed by their encyclopaedic knowledge to hypothesise this discursive meaning. This paper demonstrates the efficacy of hypothesis building using encyclopaedic knowledge and pragmatic analysis to interpret optimally relevant concept models

When natives became Africans: A historical sociolinguistic study of semantic change in colonial discourse

The word native is a key term in nineteenth-century British colonial administrative vocabulary. The question is how it comes to be central to the classification of indigenous subjects in Britain’s southern African possessions in the early twentieth century, and how the word is appropriated by colonial citizens to designate the race of indigenous subjects. To answer the question, I construct a semasiological history of native as a word that has to do with the identification of a person with a place by birth, by residence or by citizenship. I track the manner in which speakers invest old words with new meanings in specific settings and differentiate among them in different domains. In the case of native, a signal keyword is recruited to do particular work in several contemporaneous discourses which take different ideological directions as the nature of the involvement of their speakers changes. The result is a particularly complicated word history, and one which offers a clue to the ways in which colonial rhetoric is domesticated in specific settings at the very same time as the colonising power eschews it in the process of divesting itself of its colonies

Volatile concepts

This paper demonstrates the value of studying co-occurrence ‘quads’constellations of four non-adjacent lemmas that consistently co-occur across spans of up to 100 tokens– for understanding discursive change. We map meaning onto quads as ‘discursive concepts’, which encompass encyclopaedic semantics, pragmatics, and context. We investigate a highfrequency quad with high co-occurrence strength in EEBO-TCP: worldheaven-earth-power. We conduct semantic and pragmatic analysis to generate hypotheses regarding discursive change. The quad’s components are semantically underspecified; thus, although the quad indicates a discursive concept, each instantiation of the quad is variable, contingent, and dependent upon context and pragmatic processes for interpretation. We observe how the vague lexemes that constitute building blocks of religious discourse are employed to generate new, timely secular discourses; and we argue that semantic underspecification is the site and source of discursive change. Indeed, the volatile, unstable nature of the component lexical meanings renders them indispensable to early modern debate

Screening versus routine practice in detection of atrial fibrillation in patients aged 65 or over: Screening versus routine practice in detection cluster randomised controlled trial

Objectives : To assess whether screening improves the detection of atrial fibrillation (cluster randomisation) and to compare systematic and opportunistic screening. Design : Multicentred cluster randomised controlled trial, with subsidiary trial embedded within the intervention arm. Setting : 50 primary care centres in England, with further individual randomisation of patients in the intervention practices. Participants : 14,802 patients aged 65 or over in 25 intervention and 25 control practices. Interventions : Patients in intervention practices were randomly allocated to systematic screening (invitation for electrocardiography) or opportunistic screening (pulse taking and invitation for electrocardiography if the pulse was irregular). Screening took place over 12 months in each practice from October 2001 to February 2003. No active screening took place in control practices. Main outcome measure : Newly identified atrial fibrillation. Results : The detection rate of new cases of atrial fibrillation was 1.63% a year in the intervention practices and 1.04% in control practices (difference 0.59%, 95% confidence interval 0.20% to 0.98%). Systematic and opportunistic screening detected similar numbers of new cases (1.62% v 1.64%, difference 0.02%, −0.5% to 0.5%). Conclusion : Active screening for atrial fibrillation detects additional cases over current practice. The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography. Trial registration Current Controlled Trials ISRCTN19633732

A novel approach to the site-selective dual labelling of a protein via chemoselective cysteine modification

Local protein microenvironment is used to control the outcome of reaction between cysteine residues and 2,5-dibromohexanediamide. The differential reactivity is exploited to introduce two orthogonal reactive handles onto the surface of a double cysteine mutant of superfolder green fluorescent protein in a regioselective manner. Subsequent elaboration with commonly used thiol and alkyne containing reagents affects site-selective protein dual labelling