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"Murphy, Jonathan"
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Urban allies : ten brand-new collaborative stories
These collaborative stories unite two beloved characters from two different urban fantasy series in each of ten electrifying new stories.
Book
Reclaiming the Left
The Left has been charged with a lack of self-reflection and self-criticism. This article aims to address this concern through a demarcation of liberal-left values from illiberal pursuits in an attempt to reclaim (or reform) the Left to provide a genuine political opposition to the Right. Drawing together diverse perspectives, and extrapolating from direct quotations and research, four markers of extremism are identified. These markers relate to ideas of equity, culture, free speech and identity. It is hoped readers see this critique as a useful contribution in a crucial conversation on the values we want to preference in our society, a conversation we need to continue.
Journal Article
Balanced interactions of calcineurin with AKAP79 regulate Ca2+–calcineurin–NFAT signaling
The AKAP79 scaffold protein couples plasma membrane Ca
2+
influx in neurons to activation of calcineurin, which in turn activates NFAT. Analysis of this interaction shows that AKAP79 and NFAT bind the same interface on calcineurin, but the affinity of the calcineurin-AKAP79 interaction is finely balanced to promote calcineurin recruitment to the scaffold while still allowing calcineurin release for NFAT activation.
In hippocampal neurons, the scaffold protein AKAP79 recruits the phosphatase calcineurin to L-type Ca
2+
channels and couples Ca
2+
influx to activation of calcineurin and of its substrate, the transcription factor NFAT. Here we show that an IAIIIT anchoring site in human AKAP79 binds the same surface of calcineurin as the PxIxIT recognition peptide of NFAT, albeit more strongly. A modest decrease in calcineurin-AKAP affinity due to an altered anchoring sequence is compatible with NFAT activation, whereas a further decrease impairs activation. Counterintuitively, increasing calcineurin-AKAP affinity increases recruitment of calcineurin to the scaffold but impairs NFAT activation; this is probably due to both slower release of active calcineurin from the scaffold and sequestration of active calcineurin by 'decoy' AKAP sites. We propose that calcineurin-AKAP79 scaffolding promotes NFAT signaling by balancing strong recruitment of calcineurin with its efficient release to communicate with NFAT.
Journal Article
Clinical Outcomes After Percutaneous Coronary Intervention for Left Main Coronary Artery Disease in Patients of Diverse Race/Ethnicity
Data on percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) disease in patients of diverse race/ethnicity are scant. This study aimed to assess the impact of race/ethnicity on clinical outcomes at 12-month follow-up of patients with LMCA disease who underwent PCI with drug-eluting stent implantation. All patients who underwent PCI for LMCA disease between 2010 and 2019 at a tertiary care center were prospectively enrolled. Clinical outcomes were assessed per each race/ethnic group. The primary end point was the composite of all-cause death, myocardial infarction, or stroke at 12 months. A total of 774 consecutive patients with known race/ethnicity were prospectively enrolled (62.1% [n = 481] Caucasian, 17.2% [n = 133] Hispanic, 12.7% [n = 98] Asian, and 8.0% [n = 62] African-American). Compared with Caucasians, the hazard rate of the primary end point tended to be lower in Asian patients (6.1% vs 14.2%; hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.16 to 1.03) and similar in African-American (13.7% vs 14.2%; HR 0.93, 95% CI 0.40 to 2.16) and Hispanic patients (14.2% vs 14.2%; HR 1.02, 95% CI 0.58 to 1.78). Hazard rates of target vessel or lesion revascularization were comparable among the 4 groups. Cox multivariable regression adjustment confirmed consistent findings and revealed higher hazard rates of postdischarge bleeding in African-Americans compared with Caucasians (HR 5.89, 95% CI 1.00 to 34.5). In conclusion, within a racially/ethnically diverse cohort of patients who underwent PCI for LMCA disease, when compared with Caucasians, Asians had lower risk of all-cause death, myocardial infarction, or stroke, whereas African-Americans had increased risk of postdischarge bleeding.
Journal Article
Melanocortin-3 receptor regulates the normal fasting response
The melanocortin-3 receptor–deficient (MC3-R −/− ) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R −/− mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R −/− mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model.
Journal Article
Phenomenology of the sound-induced flash illusion
Past studies, using pairings of auditory tones and visual flashes, which were static and coincident in space but variable in time, demonstrated errors in judging the temporal patterning of the visual flashes—the sound-induced flash illusion. These errors took one of the two forms: under-reporting (sound-induced fusion) or over-reporting (sound-induced fission) of the flash numbers. Our study had three objectives: to examine the robustness of both illusions and to consider the effects of stimulus set and response bias. To this end, we used an extended range of fixed spatial location flash–tone pairings, examined stimuli that were variable in space and time and measured confidence in judging flash numbers. Our results indicated that the sound-induced flash illusion is a robust percept, a finding underpinned by the confidence measures. Sound-induced fusion was found to be more robust than sound-induced fission and a most likely outcome when high numbers of flashes were incorporated within an incongruent flash–tone pairing. Conversely, sound-induced fission was the most likely outcome for the flash–tone pairing which contained two flashes. Fission was also shown to be strongly driven by stimuli confounds such as categorical boundary conditions (e.g. flash–tone pairings with ≤2 flashes) and compressed response options. These findings suggest whilst both fission and fusion are associated with ‘auditory driving’, the differences in the occurrence and strength of the two illusions not only reflect the separate neuronal mechanisms underlying audio and visual signal processing, but also the test conditions that have been used to investigate the sound-induced flash illusion.
Journal Article
Predicting neointimal hyperplasia in stented arteries using time-dependant computational fluid dynamics: A review
This paper reviews the recent literature regarding the time-dependant computational fluid dynamics (CFD) analyses of blood flow through implanted coronary stents. The
in vivo processes which result in arterial restenosis are identified. The definition and range of the computationally predicted variables which are believed to stimulate the restenosis processes are evaluated. The reviewed literature is subdivided into effect-based in which the effects of altering the flow model are investigated and design-based in which different geometric stent configurations are compared. Finally, conclusions are made regarding the body of work reviewed and recommendations are provided for future work in this field.
Journal Article