Shape morphology of dipolar domains in planar and spherical monolayers.

We present a continuum theory for predicting the equilibrium shape and size of dipolar domains formed during liquid-liquid phase coexistence in planar and spherical monolayers. Our main objective is to assess the impact of the monolayer surface curvature on domain morphology. Following previous investigators, we base our analysis around minimizing the free energy, with contributions from line tension and electrostatic dipolar repulsions. Assuming a monodisperse system of circularly symmetric domains, we calculate self-energies and interaction energies for planar and spherical monolayers and determine the equilibrium domain size from the energy minima. We subsequently evaluate the stability of the circularly symmetric domain shapes to an arbitrary, circumferential distortion of the perimeter via a linear stability analysis. We find that the surface curvature generally promotes the formation of smaller, circularly symmetric domains instead of larger, elongated domains. We rationalize these results by examining the effect of the curvature on the intra- and inter-domain dipolar repulsions. We then present a phase diagram of domain shape morphologies, parameterized in terms of the domain area fraction and the monolayer curvature. For typical domain dimensions of 1-30 µm, our theoretical results are relevant to monolayers (and possibly also bilayers) in liquid-liquid phase coexistence with radii of curvature of 1-100 µm.

Interfacial rheology of coexisting solid and fluid monolayers.

Biologically relevant monolayer and bilayer films often consist of micron-scale high viscosity domains in a continuous low viscosity matrix. Here we show that this morphology can cause the overall monolayer fluidity to vary by orders of magnitude over a limited range of monolayer compositions. Modeling the system as a two-dimensional suspension in analogy with classic three-dimensional suspensions of hard spheres in a liquid solvent explains the rheological data with no adjustable parameters. In monolayers with ordered, highly viscous domains dispersed in a continuous low viscosity matrix, the surface viscosity increases as a power law with the area fraction of viscous domains. Changing the phase of the continuous matrix from a disordered fluid phase to a more ordered, condensed phase dramatically changes the overall monolayer viscosity. Small changes in the domain density and/or continuous matrix composition can alter the monolayer viscosity by orders of magnitude.

Active microrheology and simultaneous visualization of sheared phospholipid monolayers.

Two-dimensional films of surface-active agents-from phospholipids and proteins to nanoparticles and colloids-stabilize fluid interfaces, which are essential to the science, technology and engineering of everyday life. The 2D nature of interfaces present unique challenges and opportunities: coupling between the 2D films and the bulk fluids complicates the measurement of surface dynamic properties, but allows the interfacial microstructure to be directly visualized during deformation. Here we present a novel technique that combines active microrheology with fluorescence microscopy to visualize fluid interfaces as they deform under applied stress, allowing structure and rheology to be correlated on the micron-scale in monolayer films. We show that even simple, single-component lipid monolayers can exhibit viscoelasticity, history dependence, a yield stress and hours-long time scales for elastic recoil and aging. Simultaneous visualization of the monolayer under stress shows that the rich dynamical response results from the cooperative dynamics and deformation of liquid-crystalline domains and their boundaries.

Suppression of electro-osmotic flow by surface roughness.

We show that nanoscale surface roughness, which commonly occurs on microfabricated metal electrodes, can significantly suppress electro-osmotic flows when excess surface conductivity is appreciable. We demonstrate the physical mechanism for electro-osmotic flow suppression due to surface curvature, compute the effects of varying surface conductivity and roughness amplitudes on the slip velocities of a model system, and identify scalings for flow suppression in different regimes of surface conduction. We suggest that roughness may be one factor that contributes to large discrepancies observed between classical electrokinetic theory and modern microfluidic experiments.

Road traffic suicides.

A prospective observational study of fatal road traffic collisions in south-east Scotland between 1993 and 2003 revealed 17 cases (2.8% of all road fatalities) which appeared to be the result of suicide. In all 17 cases the judgement that the death was the result of suicide reflected the combination of a consistent mechanism of injury with supporting background information. The 17 individuals comprised 13 car drivers and four pedestrians. Ten of the individuals had a past history of mental illness. Only three (18%) survived to reach hospital alive. Analysis of the injuries revealed nine individuals to have unsurvivable injuries (defined by Abbreviated Injury Scale of six, Injury Severity Score of 75). The number of road traffic suicides may be generally underestimated. They appear to be difficult to prevent.

Acute abdomen as a cause of death in sudden, unexpected deaths in the elderly.

AIMS: This study profiles patients aged 70 years or above dying suddenly of an 'acute abdomen' and investigates the specific features associated with the conditions and their diagnoses. METHODS: A retrospective study using data obtained from autopsy and police reports held in the Forensic Medicine Section of the University of Edinburgh. RESULTS: From 1997 to 2000, out of 2121 autopsies of patients aged 70 or above, an 'acute abdomen' was considered as a primary cause of death in 111 cases. The number of cases increased over the period of study. Peptic ulcer disease was the commonest underlying cause of death. Twenty-nine (26.1%) cases were due to its complications, namely gastrointestinal haemorrhage and perforation. Sixty-nine (62.2%) patients were seen by a medical practitioner in circumstances arising from the onset of acute abdomen. In 27 (39.1%) cases a provisional diagnosis was recorded. CONCLUSION: The 'acute abdomen' is still an appreciably frequent cause of death in sudden, unexpected deaths in the older age group. Some of the deaths may have been preventable with an early diagnosis. A high level of vigilance and early attention to an 'acute abdomen' by medical practitioners is therefore advocated.

Stability of a charged particle in a combined Penning-Ioffe trap.

The axial symmetry of a familiar Penning trap is broken by adding the radial magnetic field of an Ioffe trap. Despite the resulting loss of a confinement theorem, stable orbits related to adiabatic invariants are identified, expressions are given for their frequencies, and resonances that must be avoided are characterized. It seems feasible to experimentally realize the new Penning-Ioffe trap to test these theoretical predictions. It also may be possible to simultaneously confine cold positrons and antiprotons in a Penning-Ioffe trap, along with any cold antihydrogen they may form.

Inhibitors of abscisic acid 8'-hydroxylase.

Structural analogues of the phytohormone (+)-abscisic acid (ABA) have been synthesized and tested as inhibitors of the catabolic enzyme (+)-ABA 8'-hydroxylase. Assays employed microsomes from suspension-cultured corn cells. Four of the analogues [(+)-8'-acetylene-ABA, (+)-9'-propargyl-ABA, (-)-9'-propargyl-ABA, and (+)-9'-allyl-ABA] proved to be suicide substrates of ABA 8'-hydroxylase. For each suicide substrate, inactivation required NADPH, increased with time, and was blocked by addition of the natural substrate, (+)-ABA. The most effective suicide substrate was (+)-9'-propargyl-ABA (K(I) = 0.27 microM). Several analogues were competitive inhibitors of ABA 8'-hydroxylase, of which the most effective was (+)-8'-propargyl-ABA (K(i) = 1.1 microM). Enzymes in the microsomal extracts also hydroxylated (-)-ABA at the 7'-position at a low rate. This activity was not inhibited by the suicide substrates, showing that the 7'-hydroxylation of (-)-ABA was catalyzed by a different enzyme from that which catalyzed 8'-hydroxylation of (+)-ABA. Based on the results described, a simple model for the positioning of substrates in the active site of ABA 8'-hydroxylase is proposed. In a representative physiological assay, inhibition of Arabidopsis thaliana seed germination, (+)-9'-propargyl-ABA and (+)-8'-acetylene-ABA exhibited substantially stronger hormonal activity than (+)-ABA itself.

Hydrodynamic coupling of two brownian spheres to a planar surface.

We describe direct imaging measurements of the collective and relative diffusion of two colloidal spheres near a flat plate. The bounding surface modifies the spheres' dynamics, even at separations of tens of radii. This behavior is captured by a stokeslet analysis of fluid flow driven by the spheres' and wall's no-slip boundary conditions. In particular, this analysis reveals surprising asymmetry in the normal modes for pair diffusion near a flat surface.

Anthracenone ABA analogue as a potential photoaffinity reagent for ABA-binding proteins.

An anthracenone analogue of abscisic acid (ABA) was synthesized as a potential photoaffinity reagent and tested for biological activity. Reaction between 10,10'-dimethoxy-9-anthrone with two equivalents of the lithiated dianion of cis-3-methylpent-2-en-4-yn-1-ol afforded an acetylenic alcohol key intermediate. Subsequent reduction of the triple bond, functional group manipulation of the side chain alcohol and deprotection of the dimethoxy protected anthrone provided anthracenone ABA analogue 7 as a potential photoaffinity reagent for ABA-binding proteins. The effect of natural ABA and the potential photoaffinity anthracenone ABA 7 on corn cell growth was determined at various concentrations. The results show that anthracenone ABA 7 is perceived as ABA-like, although producing less inhibition than ABA itself. For example, 7 at 33 microM produces approximately the same inhibition as ABA at 10 microM.

In vitro development and nutrient uptake by embryos derived from oocytes of pre-pubertal and adult cows.

The present study compared the developmental potential and uptake of nutrients by embryos from pre-pubertal and adult cows. Oocytes retrieved from ovaries of 5 to 7 month old calves and adult cows were matured and fertilized in vitro. Embryos were cultured in SOFaa to the blastocyst stage (7 days post-insemination). At successive stages of development, rates of glucose and pyruvate uptake were measured non-invasively by microfluorescence for individual embryos. Fertilization was equivalent in embryos from pre-pubertal and adult cows (P > 0.05), however development to blastocyst was significantly lower in embryos from pre-pubertal cows (9.8% versus 33.7%, respectively; P < 0.05). Total blastocyst cell number was not different between pre-pubertal and adult material (P > 0.05). Glucose uptake was exponential (pre-pubertal, r = 0.82; adult, r = 0. 82; P < 0.05), with an increase in uptake beyond the 8- to 16-cell stage. Glucose uptake was significantly lower in embryos from pre-pubertal cows at the 2- to 4-cell stages (1.5 versus 3.0 pmoles/embryo/hr; P < 0.05), but was equivalent to the adult cow at all other stages of development (P > 0.05). Pyruvate uptake was low until the blastocyst stage. Pyruvate uptake by embryos from pre-pubertal cows was significantly different to adult cows at the 1-cell stage (2.7 versus 4.6 pmoles/embryo/hr, respectively; P < 0. 05) and 2- to 4-cell stages (4.9 versus 3.6 pmoles/embryo/hr, respectively; P < 0.05). Pyruvate uptake was equivalent in the two groups in the later stages of development (P > 0.05). Perturbations in the uptake of nutrients by embryos from pre-pubertal cows were most likely due to the presence of a high proportion of developmentally incompetent embryos. Further, embryos from pre-pubertal cows that did develop to the blastocyst were as viable as blastocysts from adult cows with respect to nutrient uptakes and total cell number.

Acute myocardial ischaemia presenting as sudden death in the Lothian and Borders regions of Scotland, 1987 and 1997.

OBJECTIVES: To profile deaths from acute myocardial ischaemia presenting as sudden unexpected death in the years 1987 and 1997, and to review the diagnosis of those patients who sought medical attention. DESIGN: A retrospective study using data obtained from autopsy and police reports held in the Forensic Medicine Unit of the University of Edinburgh. RESULTS: Cardiovascular pathology was present in a significant proportion of cases. Clinically 'silent' events presenting as a sudden, unexpected death were common, comprising more than one-half of the events observed in 1987 and one-third of those in 1997. For symptomatic cases, respiratory and upper gastrointestinal symptoms were the most common presentation. The majority of patients seeking medical advice were misdiagnosed as either having a chest infection or indigestion. CONCLUSIONS: Doctors in the primary care setting should include acute myocardial ischaemia as a possible differential diagnosis of a number of symptoms which initially do not suggest a myocardial origin.

Incidence trends in house fire fatalities in eastern Scotland.

Fatal house fires occur more frequently in Scotland than elsewhere in Great Britain.(1,2) Over the last few years several educational campaigns were initiated to instruct the public in the risk factors associated with such fire fatalities and to promote the installation of functional domestic smoke detectors. An epidemiological survey of house fire deaths in the Lothian and Borders region of Scotland over the first half of the present decade, was carried out to evaluate any changing incidence trends by comparison with a survey of the fatalities from the first half of the previous decade. The impact of such campaigns in reducing house fires appears to be limited.

Hanging deaths in children.

Relatively little is known about death in children following hanging. This 12-year retrospective study in southeast Scotland revealed 12 such deaths among children <15 years of age, involving 10 boys and 2 girls. The rate of hanging deaths was 0.7 deaths/100,000 children/year and was equal to that from falls in children during this time period. The children who died following hanging were aged between 4 and 14 years. All 12 children were in cardiac arrest when found, and 11 were declared dead at the scene, demonstrating the limited potential to reduce the death rate through improved treatment. Scrutiny of the circumstances surrounding each death suggested that 6 of the deaths were accidents and 6 were suicides. There appears to be some, albeit limited, potential to prevent some hanging deaths in children through increased parental supervision, education, and restriction of access to ligatures.

Ultrasonically guided transvaginal oocyte recovery from calves treated with or without GnRH.

We investigated the effect of GnRH given after gonadotropin stimulation on follicle growth and oocyte quality in young calves in a transvaginal oocyte recovery program. A 60 mg MPA pessary was inserted into each of nineteen 5-mo-old Friesian calves for 7 d; on Day 5 they received 140 mg, s.c. FSH (Folltropin) and 200 IU, i.m. PMSG and on Day 8 ten of the calves received 40 micrograms, i.m. GnRH (Fertagyl). Follicles were measured and aspirated on Day 9 using an ultrasound unit with a 6 MHz transvaginal probe (Toshiba). Oocytes from individual calves were recovered, graded and cultured in maturation media for 2 h (+GnRH group) or 22 h (-GnRH group), then fertilized and cultured for 6 d in SOF containing 0.8% BSA and amino acids. Oocyte viability (Class A,B or C) and embryo morphology were recorded. This procedure was repeated on the 19 calves plus 5 others 1 m.o. later, after random allocation to their respective groups. Approximately 70% of the calves responded to gonadotropin stimulation (> 2 follicles over 5 mm in diameter). Calves receiving GnRH tended to have both a higher number of follicles > 2 mm in diameter (27.1 vs 18.7) and of aspirated follicles (22.0 vs 14.1); however, there was a large variability between individuals (0 to 83 follicles and 0 to 73 aspirated). The total number of oocytes collected (10.8 vs 10.9) was not affected by GnRH treatment, probably due to the poor recovery rates in the highly stimulated calves from the +GnRH group, but GnRH did improve the proportion of viable oocytes (6.5 vs 4.1) due to a lower number of Class E oocytes (1.4 vs 4.5; P < 0.05). In the GnRH group, 40% of the viable oocytes had matured at the time of collection versus 0% in the group not treated with GnRH. The necessity of different culture runs between times and treatments prevented any meaningful comparison between groups for embryo development. Following the transfer of 19 morula/blastocyst-stage embryos to recipients, 3 pregnancies were detected by ultrasound examination on Day 60, with 1 oocyte originating from the +GnRH group and 2 from the -GnRH group.

Effect of immunisation against leukaemia inhibitory factor on the establishment of pregnancy in sheep.

Leukaemia inhibitory factor (LIF), a pleiotropic cytokine, is implicated in blastocyst implantation in mice and maintains the development of ovine embryos in culture. Previously, LIF mRNA and protein were demonstrated in the endometrium throughout the oestrous cycle and early pregnancy in the ewe. In this study pregnant ewes were passively immunised against human recombinant LIF with polyclonal antibodies raised in cows by active immunisation. Ewes were immunised during two stages of early pregnancy: blastocyst development to hatching, and blastocyst elongation to implantation. Only animals passively immunised against LIF showed detectable LIF antibodies in their sera and in uterine lumina flushings by radioimmunoassay and Western blot analysis. Pregnancy was confirmed by ultrasound on day 55 and a 33.5% non-significant decrease in pregnancy rate of anti-LIF treated animals was observed, when compared to animals in control groups (untreated or treated with bovine anti-keyhole limpet hemocyanin). Cows actively immunised with recombinant human LIF and exhibiting high levels of LIF antibodies in their sera at the time of blastocyst implantation also showed a reduced pregnancy rate in comparison to control animals. Although LIF may not be obligatory for implantation in ruminants it does appear to have a role during the establishment of pregnancy.