Dynamics and excess temperature of a plume throughout its life cycle

Measurements of the velocity field associated with plumes rising through a viscous fluid are performed using stereoscopic Particle-Image Velocimetry in the Rayleigh number range 4.4 × 105 − 6.4 × 105. The experimental model is analogous to a mantle plume rising from the core-mantle boundary to the base of the lithosphere. The behaviour of the plume is studied throughout its life cycle, which is broken up into four stages; the Formation Stage, when the plume forms; the Rising Stage, when the plume rises through the fluid; the Spreading Stage, when the plume reaches the surface and spreads; and finally the Declining Stage, when the heat source has been removed and the plume weakens. The latter three stages are examined in terms of the Finite-Time Lyapunov Exponent fields and the advection of passive tracers throughout the flow. The temperature at the heater and near the fluid surface are measured using thermocouples to infer how the presence of a mantle plume would produce excess temperature near the lithosphere throughout the various stages of its life cycle. In all experiments a time lag is observed between the removal of the heat source and the decline in the excess temperature near the surface, which is proportional to the rise time. A simple analytical model is presented, which suggests that under mantle conditions (i.e. negligible thermal diffusion), the relationship between the time lag and the rise time is robust and independent of the Rayleigh number; however, the constant of proportionality is closer to unity in the absence of diffusion. Once the heat source is removed, the excess temperature near the surface declines exponentially at a rate that is inversely proportional to the rise time. The implications of this result are discussed in terms of the decline in volcanism in the Louisville hotspot chain over the past 20 Ma. The rise velocity of material in the plume is examined; the rise velocity is found to vary significantly with the plume height in a manner that is inconsistent with many of the common semi-analytical models of thermal plumes in the literature. It is also argued that this height-dependency will cause estimates of the rise velocity based on the decay series of Uranium isotopes to significantly underestimate the true value

Capn5 Expression in the Healthy and Regenerating Zebrafish Retina

PURPOSE. Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a devastating inherited autoimmune disease of the eye that displays features commonly seen in other eye diseases, such as retinitis pigmentosa and diabetic retinopathy. ADNIV is caused by a gain-of-function mutation in Calpain-5 (CAPN5), a calcium-dependent cysteine protease. Very little is known about the normal function of CAPN5 in the adult retina, and there are conflicting results regarding its role during mammalian embryonic development. The zebrafish (Danio rerio) is an excellent animal model for studying vertebrate development and tissue regeneration, and represents a novel model to explore the function of Capn5 in the eye. METHODS. We characterized the expression of Capn5 in the developing zebrafish central nervous system (CNS) and retina, in the adult zebrafish retina, and in response to photoreceptor degeneration and regeneration using whole-mount in situ hybridization, FISH, and immunohistochemistry. RESULTS. In zebrafish, capn5 is strongly expressed in the developing embryonic brain, early optic vesicles, and in newly differentiated retinal photoreceptors. We found that expression of capn5 colocalized with cone-specific markers in the adult zebrafish retina. We observed an increase in expression of Capn5 in a zebrafish model of chronic rod photoreceptor degeneration and regeneration. Acute light damage to the zebrafish retina was accompanied by an increase in expression of Capn5 in the surviving cones and in a subset of Müller glia. CONCLUSIONS. These studies suggest that Capn5 may play a role in CNS development, photoreceptor maintenance, and photoreceptor regeneration

Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

<p>Abstract</p> <p>Background</p> <p>Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks.</p> <p>Results</p> <p>We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter.</p> <p>Conclusion</p> <p>We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.</p

Riparian vegetation, Colorado River, and climate: Five decades of spatiotemporal dynamics in the Grand Canyon with river regulation

Documentation of the interacting effects of river regulation and climate on riparian vegetation has typically been limited to small segments of rivers or focused on individual plant species. We examine spatiotemporal variability in riparian vegetation for the Colorado River in Grand Canyon relative to river regulation and climate, over the five decades since completion of the upstream Glen Canyon Dam in 1963. Long-term changes along this highly modified, large segment of the river provide insights for management of similar riparian ecosystems around the world. We analyze vegetation extent based on maps and imagery from eight dates between 1965 and 2009, coupled with the instantaneous hydrograph for the entire period. Analysis confirms a net increase in vegetated area since completion of the dam. Magnitude and timing of such vegetation changes are river stage-dependent. Vegetation expansion is coincident with inundation frequency changes and is unlikely to occur for time periods when inundation frequency exceeds approximately 5%. Vegetation expansion at lower zones of the riparian area is greater during the periods with lower peak and higher base flows, while vegetation at higher zones couples with precipitation patterns and decreases during drought. Short pulses of high flow, such as the controlled floods of the Colorado River in 1996, 2004, and 2008, do not keep vegetation from expanding onto bare sand habitat. Management intended to promote resilience of riparian vegetation must contend with communities that are sensitive to the interacting effects of altered flood regimes and water availability from river and precipitation. å©2015. American Geophysical Union. All Rights Reserved

The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study

Correction to: The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study. Br Dent J (2020). https://doi.org/10.1038/s41415-020-2288-

A boarding school outbreak of pertussis in adolescents : value of laboratory diagnostic methods

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P&lt;0&middot;001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.<br /

Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome

BackgroundWe describe a severe form of congenital myasthenic syndrome (CMS) associated with congenital nephrosis and ocular malformations caused by two truncating mutations in the gene encoding the laminin beta2 subunit (LAMB2).Methods and resultsMutational analysis in the affected patient, who has a history of a serious untoward reaction to treatment with acetylcholinesterase inhibition, revealed two frame-shifting heteroallelic mutations, a maternally inherited 1478delG and a paternally inherited 4804delC. An anconeus muscle biopsy demonstrated a profound distortion of the architecture and function of the neuromuscular junction, which was strikingly similar to that seen in mice lacking laminin beta2 subunit. The findings included: pronounced reduction of the axon terminal size with encasement of the nerve endings by Schwann cells, severe widening of the primary synaptic cleft and invasion of the synaptic space by the processes of Schwann cells, and moderate simplification of postsynaptic folds and intact expression of the endplate acetylcholinesterase. The endplate potential quantal content was notably reduced, while the frequencies and amplitudes of miniature endplate potentials were only moderately diminished and the decay phases of miniature endplate potentials were normal. Western blot analysis of muscle and kidney tissue and immunohistochemistry of kidney tissue showed no laminin beta2 expression.ConclusionThis case, which represents a new type of synaptic CMS, exemplifies the wide variability of phenotypes associated with LAMB2 mutations and underscores the fundamental role that laminin beta2 plays in the development of the human neuromuscular junction

Her9/Hes4 Is Required for Retinal Photoreceptor Development, Maintenance, and Survival

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased numbers of rods and red/green cones, whereas blue and UV cones were relatively unaffected. The reduction in rods and red/green cones correlated with defects in photoreceptor subtype lineage specification. The remaining rods and double cones displayed abnormal outer segments, and elevated levels of apoptosis. In addition to the photoreceptor defects, her9 mutants also possessed a reduced proliferative ciliary marginal zone, and decreased and disorganized Müller glia. Mutation of her9 was larval lethal, with no mutants surviving past 13 days post fertilization. Our results reveal a previously undescribed role for Her9/Hes4 in photoreceptor differentiation, maintenance, and survival

Biomarkers of systemic inflammation predict survival with first-line immune checkpoint inhibitors in non-small-cell lung cancer

INTRODUCTION: Pembrolizumab is an established first-line option for patients with advanced non-small-cell lung cancer (NSCLC) expressing programmed death-ligand 1 ≥50%. Durable responses are seen in a subset of patients; however, many derive little clinical benefit. Biomarkers of the systemic inflammatory response predict survival in NSCLC. We evaluated their prognostic significance in patients receiving first-line pembrolizumab for advanced NSCLC. METHODS: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 expression ≥50% at two regional Scottish cancer centres were identified. Pretreatment inflammatory biomarkers (white cell count, neutrophil count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, albumin, prognostic nutritional index) were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) were examined. RESULTS: Data were available for 219 patients. On multivariate analysis, albumin and neutrophil count were independently associated with PFS (P 7.5 × 10(9)/l to give a three-tier categorical score. SIPS predicted PFS [hazard ratio 2.06, 95% confidence interval (CI) 1.68-2.52 (P < 0.001)] and OS [hazard ratio 2.33, 95% CI 1.86-2.92 (P < 0.001)]. It stratified PFS from 2.5 (SIPS2), to 8.7 (SIPS1) to 17.9 months (SIPS0) (P < 0.001) and OS from 5.1 (SIPS2), to 12.4 (SIPS1) to 28.7 months (SIPS0) (P < 0.001). The relative risk of death before 6 months was 2.96 (95% CI 1.98-4.42) in patients with SIPS2 compared with those with SIPS0-1 (P < 0.001). CONCLUSIONS: SIPS, a simple score combining albumin and neutrophil count, predicts survival in patients with NSCLC receiving first-line pembrolizumab. Unlike many proposed prognostic scores, SIPS uses only routinely collected pretreatment test results and provides a categorical score. It stratifies survival across clinically meaningful time periods that may assist clinicians and patients with treatment decisions. We advocate validation of the prognostic utility of SIPS in this and other immune checkpoint inhibitor treatment settings