Ocean stratification under oscillatory surface buoyancy forcing

Laboratory experiments with overturning circulation driven by oscillatory heat fluxes at one boundary are used to explore implications, for the ocean stratification, of a cyclic fluctuation in sea-surface buoyancy forcing. Fluctuations having a range of periods spanning the timescale for global recycling of the ocean volume through the thermocline are considered, with emphasis on inter-hemispheric \u27see-saw\u27 oscillations. Episodic sinking of dense water in the oceans is represented by convection in a channel with a base that is cooled over a central region and subjected to oscillatory heating near both ends, while providing a constant total heat input. For this simplified system the time-average interior temperature is found to be insensitive to the forcing period, but does vary with oscillation amplitude, whereas the interior fluctuations increase with forcing period. The circulation and density field are significantly different from those given by a steady forcing equal to the time-average of the actual oscillatory forcing, even for high-frequency oscillations. The results indicate that the overall stratification lies between that expected from the strongest phase of deep sinking and that given by symmetric sinking in both hemispheres. Glacial cycles are predicted to involve significant temperature fluctuations in the abyssal ocean. However, they are too short for the ocean to remain in quasi-equilibrium with the changing boundary conditions

The crying clarinet: Emotion and music in Parakalamos

Social narratives in Pogoni, Greece are dominated by a sense of pain that is associated with local history. This emotional trope relates directly to cultural expression, especially in terms of music. Traditional music in the village of Parakalamos is recognised locally as music that is full of pain and sorrow and is epitomised by the sound of a ‘crying clarinet’. An instrumental form of lament is central to this tradition. Yet, the pain that this music expresses is experienced as bittersweet. Rather than articulating the raw grief associated with lament in the event of a death, this form of lament is associated with a reflective bittersweet nostalgia. The same musical phrases that characterise lament accompany the dance music of the area. In this context, the sound of the crying clarinet provokes emphatic displays of joy. In the music and dance of Parakalamos, there is no conflict between pain and joy; instead they are recognised as complementary emotions. This thesis considers how emotion is conveyed through music in Parakalamos. It also looks at the relationship between musical ‘style’ and social space. The ‘Parakalamos style’ (Parakalamiótika gr. Παρακαλαμιώτικα) is created and remade in every moment of performance. In Parakalamos, style is a fluid social process. The notion of musical spontaneity or ‘inspiration’ is linked to emotional expression, and in this way improvisation is highly valued. Despite this, phrases that represent ‘crying motifs’ are frequently repeated in performance. These crying motifs embody meaning as they are connected to experiences and memories of place. This thesis considers how emotion is conveyed through music in Parakalamos. It also looks at the relationship between musical ‘style’ and social space. The ‘Parakalamos style’ (Parakalamiótika gr. Παρακαλαμιώτικα) is created and remade in every moment of performance. In Parakalamos, style is a fluid social process. The notion of musical spontaneity or ‘inspiration’ is linked to emotional expression, and in this way improvisation is highly valued. Despite this, phrases that represent ‘crying motifs’ are frequently repeated in performance. These crying motifs embody meaning as they are connected to experiences and memories of place

Drivers of change in the UK Fire Service: an operations management perspective

The UK Fire and Rescue Service is subject to reform, along with other public sector services, resulting in later retirement age and budget limitations; the fire service is also subject to other societal changes such as shifts in fitness levels and a reduction in call outs. This chapter reviews these changes and considers them from an operations management perspective. A method for how to measure operational effectiveness is proposed and its use in informing changes to operating practice in the fire service is advocated

Partitioning climate projection uncertainty with multiple large ensembles and CMIP5/6

Partitioning uncertainty in projections of future climate change into contributions from internal variability, model response uncertainty and emissions scenarios has historically relied on making assumptions about forced changes in the mean and variability. With the advent of multiple single-model initial-condition large ensembles (SMILEs), these assumptions can be scrutinized, as they allow a more robust separation between sources of uncertainty. Here, the framework from Hawkins and Sutton (2009) for uncertainty partitioning is revisited for temperature and precipitation projections using seven SMILEs and the Coupled Model Intercomparison Project CMIP5 and CMIP6 archives. The original approach is shown to work well at global scales (potential method bias < 20 %), while at local to regional scales such as British Isles temperature or Sahel precipitation, there is a notable potential method bias (up to 50 %), and more accurate partitioning of uncertainty is achieved through the use of SMILEs. Whenever internal variability and forced changes therein are important, the need to evaluate and improve the representation of variability in models is evident. The available SMILEs are shown to be a good representation of the CMIP5 model diversity in many situations, making them a useful tool for interpreting CMIP5. CMIP6 often shows larger absolute and relative model uncertainty than CMIP5, although part of this difference can be reconciled with the higher average transient climate response in CMIP6. This study demonstrates the added value of a collection of SMILEs for quantifying and diagnosing uncertainty in climate projections

Familial Infiltrative Fibromatosis (Desmoid Tumours) (MIM135290) Caused by a Recurrent 3′ APC Gene Mutation

Desmoid tumours are generally very rare but occur about 100 times more frequently in the colorectal cancer predisposition syndrome familial adenomatous polyposis (MIM 175100), being represented in about 10% of patients. In addition to desmoid disease occurring in familial adenomatous polyposis (FAP) there exist familial infiltrative fibromatosis (MIM 135290) kindreds where there is no evidence of FAP. Previously we have described a kindred with familial infiltrative fibromatosis (FIF) in which desmoid tumours were associated with nonpolyposis colorectal cancer. FAP is caused by mutations in the APC gene and various genotype-phenotype relationships have been defined including reports that colorectal polyposis is less severe with mutations 5′ to codon 157 and that the risk of desmoid tumours is high in FAP patients with APC gene mutations between codons 1444 and 1598. There is relatively little information on the phenotype of APC gene mutations 3′ to codon 1598; however, one large family has been reported with a mutation at codon 1987 which presents with a highly variable phenotype which includes desmoid disease. We screened our original FIF kindred and three further families with a similar phenotype for mutations in the APC gene. A 4 bp frameshift deletion in codon 1962 was identified in the original FIF kindred and two further apparently unrelated families. Haplotype analysis suggests a common origin for the APC mutation in all three families. Affected individuals had no evidence of congenital hypertrophy of the retinal pigment epithelium. Colorectal polyposis was variable, and most affected patients had either none or a few late onset polyps. These findings demonstrate (i) that FAP and FIF are allelic, and (ii) that APC gene mutations which truncate the APC protein distal to the beta-catenin binding domain are associated with desmoid tumours, absent CHRPE and variable but attenuated polyposis expressio

Microcavity supported lipid bilayers; evaluation of drug- lipid membrane Interactions by electrochemical impedance and fluorescence correlation spectroscopy

Many drugs have intracellular or membrane-associated targets thus understanding their interaction with the cell membrane is of value in drug development. Cell-free tools used to predict membrane interactions should replicate the molecular organization of the membrane. Microcavity array supported lipid bilayer (MSLB) platform are versatile biophysical models of the cell membrane that combine liposome-like membrane fluidity with stability and addressability. We used an MSLB herein to interrogate drugmembrane interactions across seven drugs from different classes, including non-steroidal antiinflammatories; Ibuprofen (Ibu) and Diclofenac (Dic), antibiotics; Rifampicin (Rif), Levofloxacin (Levo) and Pefloxacin (Pef), and bisphosphonates; Alendronate (Ale) and Clodronate (Clo). Fluorescence lifetime correlation spectroscopy (FLCS) and electrochemical impedance spectroscopy (EIS) were used to evaluate the impact of drug on DOPC and binary bilayers over physiologically relevant drug concentrations. Whereas FLCS data revealed Ibu, Levo, Pef, Ale and Clo had no impact on lipid lateral mobility, EIS which is more sensitive to membrane structural change, indicated modest but significant decreases to membrane resistivity consistent with adsorption but weak penetration of drugs at the membrane. Ale and Clo, evaluated at pH 5.25, did not impact the impedance of the membrane except at concentrations exceeding 4mM. Conversely, Dic and Rif dramatically altered bilayer fluidity, suggesting their translocation through the bilayer and, EIS data, showed resistivity of the membrane decreased substantially with increasing drug concentration. Capacitance changes to the bilayer in most cases were insignificant. Using a Langmuir-Freundlich model to fit the EIS data, we propose Rsat as an empirical value that reflects permeation. Overall, the data indicate that Ibu, Levo, and Pef, adsorb at the interface of the lipid membrane but Dic and Rif interact strongly, permeating the membrane core modifying the water/ion permeability of the bilayer structure. These observations are discussed in the context of previously reported data on drug permeability and Log P