Discoveries in the ruins of Niniveh and Babylon: with travels in Armenia, Kurdistan and the desert: being the result of a second expedition

H Ha Antigua 904(35) LAY/Di

The Egyptian Love Song

Transcribed by G. Dooley from manuscript in Jane Austen's hand.Duet by Henry Harington. First line: 'Sweet doth blush the rosy morning'.Jane Austen's House Museum collectio

Predicting First Traversal Times for Virions and Nanoparticles in Mucus with Slowed Diffusion

AbstractParticle-tracking experiments focusing on virions or nanoparticles in mucus have measured mean-square displacements and reported diffusion coefficients that are orders of magnitude smaller than the diffusion coefficients of such particles in water. Accurate description of this subdiffusion is important to properly estimate the likelihood of virions traversing the mucus boundary layer and infecting cells in the epithelium. However, there are several candidate models for diffusion that can fit experimental measurements of mean-square displacements. We show that these models yield very different estimates for the time taken for subdiffusive virions to traverse through a mucus layer. We explain why fits of subdiffusive mean-square displacements to standard diffusion models may be misleading. Relevant to human immunodeficiency virus infection, using computational methods for fractional subdiffusion, we show that subdiffusion in normal acidic mucus provides a more effective barrier against infection than previously thought. By contrast, the neutralization of the mucus by alkaline semen, after sexual intercourse, allows virions to cross the mucus layer and reach the epithelium in a short timeframe. The computed barrier protection from fractional subdiffusion is some orders of magnitude greater than that derived by fitting standard models of diffusion to subdiffusive data

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

International Factors and the 1964 Election

International issues are not usually seen as having been significant to the 1964 general election result. Harold Wilson made only limited references to foreign policy and defence during the campaign, while opinion polls showed that voters saw domestic questions as being far more important. Traditionally, international issues have had only a limited impact upon British general elections. But the 1964 election was one of the most closely run in history and this article argues that, interpreted broadly, international questions did have a real effect on the contest. The sitting prime minister Sir Alec Douglas-Home focused on the future of the nuclear deterrent for much of the campaign, while considerations about the country's relative decline in the world, reflected in chronic balance of payment problems, helped Labour's case that it was ‘time for a change’ at the top. Besides, the mid-1960s was a significant point for the country's global position: the post-war policy of ‘three circles’—in which Britain played a major role in Europe, maintained a global empire and influenced US policy via the ‘special relationship’—was being called into question. The question deserves to be asked, therefore, why there was not a more intense debate between the political leaders about Britain's international role

Corridor Gothic

This article investigates the role of the corridor in Gothic fiction and horror film from the late eighteenth century to the present day. It seeks to establish this transitional space as a crucial locus, by tracing the rise of the corridor as a distinct mode of architectural distribution in domestic and public buildings since the eighteenth century. The article tracks pivotal appearances of the corridor in fiction and film, and in the final phase argues that it has become associated with a specific emotional tenor, less to do with amplified fear and horror and more with emotions of Angst or dread