The inactivation of enkephalins by brain tissue

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The Stokes boundary layer for a thixotropic or antithixotropic fluid

We present a mathematical investigation of the oscillatory boundary layer (‘Stokes layer’) in a semi-infinite fluid bounded by an oscillating wall (the socalled ‘Stokes problem’), when the fluid has a thixotropic or antithixotropic rheology. We obtain asymptotic solutions in the limit of small-amplitude oscillations, and we use numerical integration to validate the asymptotic solutions and to explore the behaviour of the system for larger-amplitude oscillations. The solutions that we obtain differ significantly from the classical solution for a Newtonian fluid. In particular, for antithixotropic fluids the velocity reaches zero at a finite distance from the wall, in contrast to the exponential decay for a thixotropic or a Newtonian fluid. For small amplitudes of oscillation, three regimes of behaviour are possible: the structure parameter may take values defined instantaneously by the shear rate, or by a long-term average; or it may behave hysteretically. The regime boundaries depend on the precise specification of structure build-up and breakdown rates in the rheological model, illustrating the subtleties of complex fluid models in non-rheometric settings. For larger amplitudes of oscillation the dominant behaviour is hysteretic. We discuss in particular the relationship between the shear stress and the shear rate at the oscillating wall

High-resolution mapping of cancer cell networks using co-functional interactions.

Powerful new technologies for perturbing genetic elements have recently expanded the study of genetic interactions in model systems ranging from yeast to human cell lines. However, technical artifacts can confound signal across genetic screens and limit the immense potential of parallel screening approaches. To address this problem, we devised a novel PCA-based method for correcting genome-wide screening data, bolstering the sensitivity and specificity of detection for genetic interactions. Applying this strategy to a set of 436 whole genome CRISPR screens, we report more than 1.5 million pairs of correlated "co-functional" genes that provide finer-scale information about cell compartments, biological pathways, and protein complexes than traditional gene sets. Lastly, we employed a gene community detection approach to implicate core genes for cancer growth and compress signal from functionally related genes in the same community into a single score. This work establishes new algorithms for probing cancer cell networks and motivates the acquisition of further CRISPR screen data across diverse genotypes and cell types to further resolve complex cellular processes

The Functional Consequences of Variation in Transcription Factor Binding

One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This combination of data allowed us to infer functional TF binding. On average, 14.7% of genes bound by a factor were differentially expressed following the knockdown of that factor, suggesting that most interactions between TF and chromatin do not result in measurable changes in gene expression levels of putative target genes. We found that functional TF binding is enriched in regulatory elements that harbor a large number of TF binding sites, at sites with predicted higher binding affinity, and at sites that are enriched in genomic regions annotated as active enhancers.Comment: 30 pages, 6 figures (7 supplemental figures and 6 supplemental tables available upon request to [email protected]). Submitted to PLoS Genetic

All-sky signals from recombination to reionization with the SKA

Cosmic evolution in the hydrogen content of the Universe through recombination and up to the end of reionization is expected to be revealed as subtle spectral features in the uniform extragalactic cosmic radio background. The redshift evolution in the excitation temperature of the 21-cm spin flip transition of neutral hydrogen appears as redshifted emission and absorption against the cosmic microwave background. The precise signature of the spectral trace from cosmic dawn and the epoch of reionization are dependent on the spectral radiance, abundance and distribution of the first bound systems of stars and early galaxies, which govern the evolution in the spin-flip level populations. Redshifted 21 cm from these epochs when the spin temperature deviates from the temperature of the ambient relic cosmic microwave background results in an all-sky spectral structure in the 40-200 MHz range, almost wholly within the band of SKA-Low. Another spectral structure from gas evolution is redshifted recombination lines from epoch of recombination of hydrogen and helium; the weak all-sky spectral structure arising from this event is best detected at the upper end of the 350-3050 MHz band of SKA-mid. Total power spectra of SKA interferometer elements form the measurement set for these faint signals from recombination and reionization; the inter-element interferometer visibilities form a calibration set. The challenge is in precision polarimetric calibration of the element spectral response and solving for additives and unwanted confusing leakages of sky angular structure modes into spectral modes. Herein we discuss observing methods and design requirements that make possible these all-sky SKA measurements of the cosmic evolution of hydrogen.Comment: Accepted for publication in the SKA Science Book 'Advancing Astrophysics with the Square Kilometre Array', to appear in 201

Boys on Blue Benches: Disfigured Veterans of the First World War

The First World War saw a multitude of facial wounds, with veterans coming home with severe facial mutilation numbering in the thousands. These veterans have been somewhat overlooked in the historiography of medicine in World War I, and this work seeks to remedy that by examining every aspect of their lives, from the moment of the wound, to the aftermath of their return home. The medical professionals who treated these men gave a great deal of thought to the philosophy behind their work, and frequently voiced the opinion that their work was essential for the wellness of these men’s psyches. This is because patients with facial wounds experienced a double trauma, resulting in both the loss of function and the loss of psychic identity. If surgeons were unsuccessful in covering over severe wounds, sculptors stepped in to take over for them, crafting fine tin masks for the men to wear until they themselves expired. The masks came to serve as a visual reminder of medicine’s inability to cover the wounds of war. Finally, these men experienced unpleasant reactions upon returning home, because their wounds did not fit in with the way that Europeans preferred to memorialize the First World War. The personal accounts of soldiers and medical workers speak to this notion

Wandering Souls: Protestant Migrations in America, 1630–1865

Review of: "Wandering Souls: Protestant Migrations in America, 1630–1865," by S. Scott Rohrer

Investigating understandings of age in the workplace

Age in the workplace has become a hot topic of debate across different countries and sectors. Yet, to date, age has been one of the least researched aspects of diversity at work. Instead, we tend to assume certain ‘facts’ about how age affects people’s ability to work, usually informed by stereotypes about the talents and capabilities of different age groups and generational categories. In this research, we aimed to scrutinise such stereotypes, exploring how they are constructed and their potential effect on experiences of work and employment across different age groups in the UK