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Seasonal migration and natal dispersal represent the major large-scale movements in the lives of animals. Individuals that are relatively prone to movement and exploration might thus be more likely to disperse and also to migrate farther. Such movement might be either negatively associated with parasitic infection (if infection prevents hosts from successful long-distance migration) or positively associated (e.g. if longer-distance migrants encounter more abundant or more diverse parasites). We examined whether natal dispersal tendency predicts seasonal migration distance in song sparrows (Melospiza melodia) and whether migration distance predicts infection with bloodborne parasites upon arrival at the breeding grounds. Migration distance, inferred from stable hydrogen isotope analysis (δ2H) of winter-grown tissue, was repeatable (repeatability = 0.41) over years. Birds that were more likely to have immigrated from outside the breeding grounds, as inferred from genetic assignment tests, also overwintered farther south, as inferred from stable isotope analysis. The finding that individuals more prone to movement in the context of natal dispersal also tended to travel farther, on average, in the context of seasonal migration suggests consistent individual variation in large-scale movements across these two contexts. Although statistically significant, this effect was modest in scope and subtle relative to sex differences in inferred migration distance. Among after-second-year individuals, but not yearlings, longer-distance migrants were more likely, on average, to be infected with bloodborne parasites. Individual variation in propensity to long-distance movement may interact with age-related variation in exposure or susceptibility to parasites, to shape the role of animal migration in transporting infectious disease. In many animal species, individuals vary consistently in activity and movement over small geographic scales. Large-scale movements such as seasonal migration are of particular interest because they can influence disease risk, but until recently, such movements have been difficult to track. We used stable isotope analysis to estimate overwintering latitude of song sparrows returning to their breeding grounds. Individuals overwintering farther south were also more likely to have immigrated from outside the breeding site, indicating that movement is correlated across the contexts of migration and dispersal. Rates of infection with bloodborne parasites increased with migration distance in older birds, but not in yearlings. Our findings suggest that individual variation in movement may interact with age-related variation in infection risk, to shape the role of animal migration in transporting parasites.

The molecular mechanisms of luminal cell differentiation are not understood well enough to determine how differentiation goes awry during oncogenesis. Using RNA-Seq analysis, we discovered that CREB1 plays a central role in maintaining new luminal cell survival and that oncogenesis dramatically changes the CREB1-induced transcriptome. CREB1 is active in luminal cells, but not basal cells. We identified ING4 and its E3 ligase, JFK, as CREB1 transcriptional targets in luminal cells. During luminal cell differentiation, transient induction of ING4 expression is followed by a peak in CREB1 activity, while JFK increases concomitantly with CREB1 activation. Transient expression of ING4 is required for luminal cell induction; however, failure to properly down-regulate ING4 leads to luminal cell death. Consequently, blocking CREB1 increased ING4 expression, suppressed JFK, and led to luminal cell death. Thus, CREB1 is responsible for the suppression of ING4 required for luminal cell survival and maintenance. Oncogenic transformation by suppressing PTEN resulted in constitutive activation of CREB1. However, the tumor cells could no longer fully differentiate into luminal cells, failed to express ING4, and displayed a unique CREB1 transcriptome. Blocking CREB1 in tumorigenic cells suppressed tumor growth in vivo, rescued ING4 expression, and restored luminal cell formation, but ultimately induced luminal cell death. IHC of primary prostate tumors demonstrated a strong correlation between loss of ING4 and loss of PTEN. This is the first study to define a molecular mechanism whereby oncogenic loss of PTEN, leading to aberrant CREB1 activation, suppresses ING4 expression causing disruption of luminal cell differentiation.

Sequential treatment of a previously-calcined solid oxide support (i.e. SiO2, γ-Al2O3, or mixed SiO2–Al2O3) with solutions of Cr{N(SiMe3)2}3 (0.71 wt% Cr) and a Lewis acidic alkyl aluminium-based co-catalyst (15 molar equivalents) affords initiator systems active for the oligomerisation and/or polymerisation of ethylene. The influence of the oxide support, calcination temperature, co-catalyst, and reaction diluent on both the productivity and selectivity of the immobilised chromium initiator systems have been investigated, with the best performing combination (SiO2−600, modified methyl aluminoxane-12 {MMAO-12}, heptane) producing a mixture of hexenes (61 wt%; 79% 1-hexene), and polyethylene (16 wt%) with an activity of 2403 g gCr−1 h−1. The observed product distribution is rationalised by two competing processes: trimerisation via a supported metallacycle-based mechanism and polymerisation through a classical Cossee-Arlman chain-growth pathway. This is supported by the indirect observation of two distinct chromium environments at the surface of the oxide support by a solid-state 29Si NMR spectroscopic study of the Cr{N(SiMe3)2}x/SiO2−600 pro-initiator. Electronic supplementary material The online version of this article (10.1007/s11244-018-0891-8) contains supplementary material, which is available to authorized users.

In vertebrate animals, genes of the major histocompatibility complex (MHC) determine the set of pathogens to which an individual's adaptive immune system can respond. MHC genes are extraordinarily polymorphic, often showing elevated nonsynonymous relative to synonymous sequence variation and sharing presumably ancient polymorphisms between lineages. These patterns likely reflect pathogen‐mediated balancing selection, for example, rare‐allele or heterozygote advantage. Such selection is often reinforced by disassortative mating at MHC. We characterized exon 2 of MHC class II, corresponding to the hypervariable peptide‐binding region, in song sparrows (Melospiza melodia). We compared nonsynonymous to synonymous sequence variation in order to identify positively selected sites; assessed evidence for trans‐species polymorphisms indicating ancient balancing selection; and compared MHC similarity of socially mated pairs to expectations under random mating. Six codons showed elevated ratios of nonsynonymous to synonymous variation, consistent with balancing selection, and we characterized several alleles similar to those occurring in at least four other avian families. Despite this evidence for historical balancing selection, mated pairs were significantly more similar at MHC than were randomly generated pairings. Nonrandom mating at MHC thus appears to partially counteract, not reinforce, pathogen‐mediated balancing selection in this system. We suggest that in systems where individual fitness does not increase monotonically with MHC diversity, assortative mating may help to avoid excessive offspring heterozygosity that could otherwise arise from long‐standing balancing selection.

Purpose To measure right ventricular (RV) trabecular complexity by its fractal dimension (FD) in healthy subjects and patients with pulmonary hypertension (PH) and to assess its relationship with hemodynamic and functional parameters and future cardiovascular events. Materials and Methods This retrospective study used data acquired from May 2004 to October 2013 in 256 patients with newly diagnosed PH who underwent cardiac MRI, right-sided heart catheterization, and 6-minute walk distance testing, with median follow-up of 4.0 years. A total of 256 healthy control subjects underwent cardiac MRI only. Biventricular FD, volumes, and function were assessed on short-axis cine images. Reproducibility was assessed with the intraclass correlation coefficient, correlation between variables was assessed with the Pearson correlation test, and mortality prediction was compared by using uni- and multivariable Cox regression analyses. Results RV FD reproducibility had an intraclass correlation coefficient of 0.97 (95% confidence interval [CI]: 0.96, 0.98). RV FD was higher in patients with PH (median, 1.310; interquartile range [IQR], 1.281-1.341) than in healthy subjects (median, 1.264; IQR, 1.242-1.295; P.001), with the greatest difference near the apex. RV FD was associated with pulmonary vascular resistance (r = 0.30, P.001). At univariable Cox regression analysis, RV FD was a significant predictor of death (hazard ratio [HR], 1.256; 95% CI: 1.011, 1.560; P = .04); however, at multivariable analysis, RV FD did not enable prediction of survival independently of conventional parameters of RV remodeling (HR, 1.179; 95% CI: 0.871, 1.596; P = .29). Conclusion Fractal analysis of RV trabecular complexity is a highly reproducible measure of remodeling in patients with PH that is associated with afterload, although the gain in survival prediction over traditional markers is not significant. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

The major histocompatibility complex (MHC) plays a key role in vertebrate immunity, and pathogen-mediated selection often favours certain allelic combinations. Assessing potential mates' MHC profiles may provide receivers with genetic benefits (identifying MHC-compatible mates and producing optimally diverse offspring) and/or material benefits (identifying optimally diverse mates capable of high parental investment). Oscine songbirds learn songs during early life, such that song repertoire content can reflect population of origin while song complexity can reflect early life condition. Thus birdsong may advertise the singer's genetic dissimilarity to others in the population (and, presumably, compatibility with potential mates), or individual genetic diversity (and thus condition-dependent material benefits). We tested whether song repertoire content and/or complexity signal MHC class IIβ dissimilarity and/or diversity in male song sparrows ( Melospiza melodia ). Pairwise dissimilarity in repertoire content did not predict MHC dissimilarity between males, suggesting that locally rare songs do not signal rare MHC profiles. Thus, geographical variation in song may not facilitate MHC-mediated inbreeding or outbreeding. Larger repertoires were associated with intermediate MHC diversity, suggesting intermediate rather than maximal MHC diversity is optimal. This could reflect trade-offs between resisting infection and autoimmune disorders. Song complexity may advertise optimal MHC diversity, a trait affecting disease resistance and capacity for parental care.

Summary Assessment tools must be investigated for reliability, validity and feasibility before being implemented. In 2013, the Australian and New Zealand College of Anaesthetists introduced workplace-based assessments, including a direct observation of a procedural skills assessment tool. The objective of this study was to evaluate the psychometric properties of this assessment tool for ultrasound-guided regional anaesthesia. Six experts assessed 30 video-recorded trainee performances of ultrasound-guided regional anaesthesia. Inter-rater reliability, assessed using absolute agreement intraclass correlation coefficients, varied from 0.10 to 0.49 for the nine individual nine-point scale items, and was 0.25 for a ‘total score’ of all items. Internal consistency was measured by correlation between ‘total score’ and ‘overall performance’ scale item (r = 0.68, p

In jawed vertebrates, genes of the major histocompatibility complex (MHC) play a key role in immunity by encoding cell-surface proteins that recognize and bind non-self antigens. High variability at MHC suggests that these loci may also function in social signalling such as mate choice and kin recognition. This requires that MHC genotype covaries with some perceptible phenotypic trait. In mammals and fish, MHC is signalled chemically through volatile and non-volatile peptide odour cues, facilitating MHC-dependent mate choice and other behaviours. In birds, despite evidence for MHC-dependent mating, candidate mechanisms for MHC signalling remain largely unexplored. However, feather preen wax has recently been implicated as a potential source of odour cues. We examined whether the chemical composition of preen wax correlates with MHC class IIβ genotypes of wild song sparrows ( Melospiza melodia ). Pairwise chemical distance reflected amino acid distance at MHC for male–female dyads, although not for same-sex dyads. Chemical diversity did not reflect MHC diversity. We used gas chromatography–mass spectrometry (GC-MS) to characterize preen wax compounds, and identified four wax esters that best reflect MHC similarity. Provided songbirds can detect variation in preen wax composition, this cue may allow individuals to assess MHC compatibility of potential mates.

Flexible power transmission couplings are a vital part in the drive train of rotorcraft, conventional aircraft and other land, sea and marine propulsion systems. These components are generally subject to high torque, rotational speeds and temperatures, which result in high static and dynamic loads that make them susceptible to degradation and failure. Additionally, couplings can experience accelerated failures, mainly driven by high cyclic stresses induced by extreme shaft misalignment and secondary causes such as improper assembly, fastener damage and lubricant loss. Damage to other drive train components can also lead to increased vibration and misalignment which, in turn, induces coupling failure. As with many complex systems, the service life of a shaft is randomly distributed and can be modelled by a stochastic deterioration process that allows approximation of remaining useful life (RUL). However, in such an approach, knowledge of actual shaft damage (ie current crack size) is still required. In practical health monitoring applications, actual damage is estimated via inference, as it is nearly impossible to be measured directly. To address this critical need, a shaft and shaft coupling prognostics and health management (PHM) system was developed that integrates vibration diagnostics, finite element stress analysis and material fatigue modelling to predict RUL of helicopter drive shafts and flexible shaft couplings. This modelling and prediction approach was developed and validated against actual sub-scale failure testing that included the requisite measurement of the ‘ground truth’ damage level. Data from a scaled drive shaft/ coupling test stand was used to validate the approach. The results indicated a cumulative prognostic accuracy of 80% over the last 25 minutes of the coupling life. Vibration-based diagnostics helped to improve the accuracy to over 95% once a crack had initiated and been detected over the last five minutes of coupling life. The application of these technologies will establish an economical, safe and effective maintenance-scheduling regime for helicopter shafts and couplings by scheduling maintenance towards the end of actual component life, increasing availability by preventing unscheduled maintenance and reducing inspections.

PCR conditions, procedure for determining error threshold for next-generation sequencing, comparison of genomic vs cDNA-derived MHC sequences

Compounds identified by GC-MS of song sparrow preen wax

The Severn Estuary provides the UK with a unique opportunity to harness a large amount of renewable energy from the tides. A barrage 10 miles (16 km) long has been proposed as a means of harnessing this energy. The scheme would be similar, but on a larger scale, to that in the Rance Estuary, northern France, which has consistently and predictably produced electricity over the last 40 years. The studies presented here illustrate the output patterns of the Severn Barrage once the barrage is closed but before project completion, taking into consideration important factors such as: National Grid integration; environmental sensitivities and turbine and pumping characteristics. Assuming the main determine and of operating procedure is production of maximum energy, total barrage output could be 33 TWh by project completion. This is equivalent to almost two years of output from the completed scheme. Furthermore, if barrage closure were to occur earlier than previously envisaged, significantly more electricity would be produced during the construction phase, thus further enhancing the projects economic prospects.

The predictable, regular reversal of the tides makes this an important renewable energy resource, one which is large, technically well proven and reliable if exploited by applying the conventional principles of hydroelectric power. The basic operating principles of tidal power stations were explored in depth in many studies carried out throughout the twentieth century. With few exceptions, a basic premise was to maximise energy output. Less attention was given to identifying the design and operating procedures needed to maximise aggregated energy value, it presumably being assumed that the latter followed the former. The studies reported in this paper are based on the now strongly established commercial trend for electricity to be marketed competitively, having regard for such factors as time of day and guarantee of use. Consumer technologies have taken advantage of the differential tariff structures which have emerged and will continue to evolve, and this in turn is being reflected in the composition of the supply industry. The much-valued versatility of hydro generation applies equally to tidal power plant. The opportunities for a tidal barrage to be operated flexibly, having regard for fundamental resource constraints, are set out, though without regard for tariff structures because these will depend on the particular network conditions in which any project will operate. The studies have been carried out in the context of a Severn Estuary barrage.

Low head, doubly-regulated (Kaplan) axial flow turbines are well suited to working in reverse as pumps. For good efficiency in both operations, the generating and pumping heads must be complementary. The Rance tidal power scheme in Brittany has been carrying out matched generating and pumping operations to good effect since it was commissioned in 1966. Some simplifications to the range of operations performed at Rance have been identified. There is also potential for these operations to be extended, in particular to make greater use of pumping now that energy storage promises to become a more important function of electricity network operation. The results of the studies reported here explore this opportunity, together with its associated benefit of allowing the timing of generation from the enhanced resource to be varied to best suit that of energy demands.

Reovirus attachment to cells is mediated by the binding of viral attachment protein σ1 to junctional adhesion molecule 1 (JAM1). The crystal structure of the extracellular region of human JAM1 (hJAM1) reveals two concatenated Ig-type domains with a pronounced bend at the domain interface. Two hJAM1 molecules form a dimer that is stabilized by extensive ionic and hydrophobic contacts between the N-terminal domains. This dimeric arrangement is similar to that observed previously in the murine homolog of JAM1, indicating physiologic relevance. However, differences in the dimeric structures of hJAM1 and murine JAM1 suggest that the interface is dynamic, perhaps as a result of its ionic nature. We demonstrate that hJAM1, but not the related proteins hJAM2 and hJAM3, serves as a reovirus receptor, which provides insight into sites in hJAM1 that likely interact with σ1. In addition, we present evidence that the previously reported structural homology between σ1 and the adenovirus attachment protein, fiber, also extends to their respective receptors, which form similar dimeric structures. Because both receptors are located at regions of cell–cell contact, this similarity suggests that reovirus and adenovirus use conserved mechanisms of entry and pathways of infection.

All major JET systems have been fully commissioned for D-T and the DTE1 series of experiments has started with the D-T fuel mixture and operating conditions foreseen for ITER. In the area of ITER physics, significant results have been produced in both D-D and D-T. In D-D, the LH threshold power database has been extended, the bounds on edge-electron temperature and density in ELMy H-modes have been defined and the advantages of Types I and III ELMy discharges have been compared. In D-T plasmas, the isotope effect on H-mode threshold power and transport has been determined so that a more accurate assessment can be made of the ignition margin and heating requirements for ITER. Trace tritium experiments have provided first particle transport measurements and an assessment of the ITER reference ion-cyclotron resonance-frequency heating scenarios has been started, In the area of fusion performance, record D-D neutron yields have been obtained by controlling the plasma and current profiles in hot ion ELM-free H-modes and optimized shear modes. In D-T, internal transport barriers have been readily established in optimized shear discharges and Alfven eigenmodes have been observed.

The orientational alignment of anisotropic colloidal particles in an electric field arises from a coupling of the field with any permanent or induced dipole moments. With suitable frequency alternating fields, only the latter are effective. They have their origins in the anisotropy of the electrical polarizability (∆ α ) of the particles or of the electric double layer. This parameter depends upon particle size and there is a need to evaluate this dependence experimentally and theoretically for various frequently encountered geometries. This study reports the measurement of the electric birefringence of aqueous suspensions of lozenge and rod-like polytetrafluoroethylene particles and of kaolin disc-like platelets simultaneously with a full size characteri­zation of the samples. Allowance is made for sample polydispersity. In the general equation where ∆ α is proportional to I s , the parameter S has the values of 3, 2 and 2 for the near-spherical lozenges, the fibrous and the discotic particles respectively. Theoretical implications are discussed. The versatility of the electric birefringence method for characterization of the size and electrical properties of colloidal particles is evident.

OBJECTIVE The best dynamic test for the assessment of the hypothalamic–pituitary–adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic–pituitary–adrenal axis. DESIGN Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING Programmed Investigation Unit. SUBJECTS Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycaemia (plasma glucose 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

The JET neutral beam injection system has proved to be both effective and reliable as a plasma heating device. The ion heating and plasma fuelling characteristics of the system are ideally suited to the production of high fusion performance plasmas while the flexibility in the choice of beam species (H, D, T, 3 He or 4 He) and the ability to inject into almost any JET plasma configuration allows a wide variety of related physics experiments to be carried out. The capability to inject (for the first time) tritium beams was essential to the successful execution of the first tritium experiments in which 1.7 MW of power from DT fusion reactions was generated.

An account is given of the high performance plasmas established by development of the H-mode regime in JET in the experimental campaigns up to 1992. High performance in this case is measured in terms of the confinement enhancement achieved over the L-mode scaling as measured using the plasma diamagnetism. Three JET H-mode regimes have achieved enhancement factors (H G DIA ) over Goldston L-mode scaling of 2.5 < H G DIA < 4.0. These are the Pellet Enhanced Performance (PEP) H-MODE, the high bootstrap fraction (high β POL ) H-mode and the Hot Ion (HI) H-mode. The phenomenology of these three regimes is reviewed and contrasts and common threads are elucidated

We describe a sample cell capable of attaining 100% relative humidity that is suitable for the study of aligned lipid multibilayers using x-ray diffraction. The basic principles of this cell are applicable to sample environments used in a variety of physical techniques (e.g., nuclear magnetic resonance, light scattering, infrared spectroscopies, etc.) thus enabling these techniques, for the first time, to study aligned samples having the same physical characteristics (i.e., repeat spacing, transition temperature, etc.) as their liposomal counterparts immersed in water.

In this study we examined the effects of insulin on protein kinase C (PKC) activity in cultured fetal chick neurons. PKC activity, measured as 32P incorporation into histone H1 in the presence of calcium (500 microM), phosphatidylserine (100 micrograms/ml), and diolein (3.3 micrograms/ml) minus the incorporation in the presence of calcium alone, was detected in neuronal cytosolic (207 +/- 33 pmol/min/mg) and membrane (33 +/- 8 pmol/min/mg) fractions. Insulin added to intact neurons increased the activity of PKC in both cytosolic and membrane fractions by about 40%. Neurons preincubated with cycloheximide (10 micrograms/ml) 30 min prior to insulin treatment showed the same degree of stimulation of PKC activity by insulin. The activation of PKC was maximal within 5-10 min of insulin exposure and was sustained for at least 60 min. Insulin stimulated PKC in a dose-dependent manner, with a maximal response obtained at 100 ng/ml. Addition of phosphatidylserine and diolein to neuronal cell extracts resulted in the phosphorylation of four major cytosolic proteins (70, 57, 18, and 16 kDa) and one major membrane protein (75 kDa). Phosphorylation of all five proteins was increased 2-fold in extracts from insulin-treated neurons. Immunoblot analysis of whole cell extracts using antibodies against PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon revealed that cultured fetal chick neurons contained only one of these PKC isoforms, the epsilon-isoform. The enzyme was mostly cytosolic. Insulin had no effect on either the amount of distribution of PKC-epsilon in cultured neurons but induced a small change in the mobility of PKC-epsilon on sodium dodecyl sulfate-polyacrylamide gels. When assay conditions were designed to measure specifically the activity of PKC-epsilon, using a synthetic peptide substrate in the absence of calcium, activity was 50 +/- 12% higher in insulin-treated cells (p less than 0.005). PKC activity in control and insulin treated-neurons was almost completely inhibited when assays included a peptide identical to the pseudo-substrate binding site of PKC-epsilon. We conclude that PKC-epsilon is the major PKC isoform present in cultured fetal chick neurons. Insulin stimulates PKC-epsilon activity by a mechanism that does not involve translocation of the enzyme from cytosol to membrane.

As oilfield developments become more technically and economically challenging, Flow Assurance has become crucial to the feasibility of projects. Consequently, Flow Assurance issues, such as hydrates or wax deposition must now be considered early in concept selection. Modern numerical methods, coupled with the latest software engineering techniques, now allow the rigorous calculation of multiphase thermal-hydraulic behaviour in an integrated asset model (IAM) on timescales acceptable for concept selection. The paper describes the application of a new IAM tool to analyse options for the development of fields in the Western part of BP's Angolan deepwater Block 18. Novel aspects include the embedding of field scheduling rules such that the drilling schedules were predicted automatically from the model. In addition, different field architectures were considered, including tubing and pipeline sizes, looping of pipelines and subsea multiphase boosting, and the impact on production rates and drilling schedules was quantified. Furthermore, the option to tie back to the planned Greater Plutonio FPSO was also modelled with the forecast ullage profile being imposed on production from the new fields. All calculations were performed using rigorous multiphase thermal-hydraulic models allowing Flow Assurance constraints to be analysed simultaneously.

Using neutron diffraction and a specially constructed high pressure cell suitable for aligned multibilayer systems, we have studied, as a function of pressure, the much observed anomalous swelling regime in dimyristoyl- and dilauroyl-phosphatidylcholine bilayers, DMPC and DLPC, respectively. We have also reanalyzed data from a number of previously published experiments and have arrived at the following conclusions. (a). The power law behavior describing anomalous swelling is preserved in all PC bilayers up to a hydrostatic pressure of 240 MPa. (b). As a function of increasing pressure there is a concomitant decrease in the anomalous swelling of DMPC bilayers. (c). For PC lipids with hydrocarbon chainsor=13 carbons the theoretical unbinding transition temperature T small star, filled is coupled to the main gel-to-liquid crystalline transition temperature T(M). (d). DLPC is intrinsically different from the other lipids studied in that its T small star, filled is not coupled to T(M). (e). For DLPC bilayers we predict a hydrostatic pressure (290 MPa) where unbinding may occur.

We describe a temperature controlled sample cell suitable for the study of biomimetic materials (e.g., lipid bilayers) using neutron diffraction, and capable of exerting hydrostatic pressures of up to 370 MPa. The advantage of this sample cell, compared to previous high-pressure cells of its type, is that it allows for the use of samples aligned on a solid support which, compared to “powder” or so-called liposomal preparations, requires only small amounts of sample and allows for the clear differentiation between in-plane and out-of-plane structure.

Scene simulation has proved to be a valuable tool for analysing the images perceived by visible and infrared imaging systems. Accurate scene simulation requires accurate incorporation of the optical properties of all the materials within a scene, with reflectance incorporated with the bidirectional reflectance distribution function (BRDF) and emission incorporated through the directional emissivity or hemispherical directional reflectance (HDR). This paper compares the fit of various parameterised models to experimental BRDF data from a variety of surfaces representing the extremes of material properties found in the environment. One of the main aims is to infer the accuracy and validity of an in-house BRDF model called Mopaf using data representative of different sorts of isotropically reflecting materials. Where appropriate physical and semiempirical models and a novel parameter based BRDF model were compared with Mopaf and with BRDF data from a Surface Optics Corporation SOC-200 instrument. It was concluded that Mopaf might not be reliable for all the angular BRDF data, especially specularly reflecting surfaces or grazing incidence data. Likewise, the other BRDF models investigated tended to be limited to a range of physical conditions such as only diffuse reflection or to a range of surface roughness. It was shown that the proposed new BRDF model was more generally applicable from the visible to infrared wavelengths, over a wide range of reflection angles and for different sorts of surface material.

We report the misleading sonographic appearance of Surgicel in the diagnosis of renal vein thrombosis in a case of kidney transplant and a review of the literature. Removal of the Surgicel before closure is advisable to avoid misdiagnosis.

Mingos et al. have prepared two isomers of the cluster compound (Rh{sub 2}(mu-Cl{sub 2})(CNC{sub 8}H{sub 9}){sub 4}(mu-AuPPh{sub 3})){sub 2}(PF{sub 6}){sub 2} and have characterized these isomers using single crystal x-ray techniques. The volumes per cluster cation were found to be very similar for both isomers, 1,430 and 1,413 angstroms, and the Rh-Rh bond lengths were found to be 3.262 and 3.008 angstroms for the same isomer. The cluster skeletal geometries were found to differ only at an interior link, and applied pressure appeared to induce a conformational transition around this bond.

There has been increasing interest in the measurement, validation, and parameterization of the bidirectional reflectance distribution function (BRDF) from surface coatings for image simulation and rendering, and design models of coating systems. The complexity of data required depends on the finish or final appearance of the surface coating. In particular the development of optical effect pigments places heightened requirements on the BRDF data needed for adequate characterization of a surface coating. Measurements of the BRDF are presented from pigmented films representative of the top layer of a paint coating. The measurements investigate the scattering characteristics of pearlescent pigments as a function of the incident polar angle and the polar and azimuthal scatter angles, including a study of the spectral variation of the BRDF across the visible waveband from 350 nm to 800 nm. In addition, measurements of linearly polarized BRDF as a function of incident and reflected directions are reported. The measurements emphasize the various optical properties of coatings such as surface and volume scattering and polarization contributions, which need to be considered if the data is to be accurately modelled or parameterized and used effectively.

1. The nature of the membrane channels underlying the membrane conductance changes induced by the nitric oxide (NO) donors, S-nitroso-L-cysteine (NOCys) and sodium nitroprusside (SNP) were investigated in single myocytes isolated from the circular muscle layer of the guinea-pig proximal colon, by use of standard whole-cell and single channel recording techniques. 2. Under voltage clamp, depolarizing steps from -60 mV elicited a rapidly-developing, little-inactivating outward K+ current (IK) at potentials positive to -40 mV (at 20-25 degrees C). The steady-state level (ISS) of this K current increased in amplitude as the step potential was made to more positive potentials. If the depolarizing steps were made from a holding potential of -80 mV an additional rapidly activating and inactivating outward K+ current was also elicited, superimposed on IK. 3. At 20-25 degrees C, NOCys (2.5 microM), SNP (100 microM) and 8-bromo-cyclic GMP (500 microM) increased the amplitude of ISS of IK elicited from a holding potential of -60 mV. In contrast, NOCys (2-5 microM) had little effect on ISS at 35 degrees C. Higher concentrations (or = 5 microM at 20-25 degrees C andor = 10 microM at 35 degrees C) of NOCys decreased the peak amplitude (I[Peak]) and ISS of IK in a concentration-dependent manner. This blockade of IK with NOCys was always associated with an increase of the holding current (IHold), due to the activation of a membrane conductance with a reversal potential between 0 and + 30 mV and which was reduced approximately 50% upon the addition of Cd2+ (1 mM). 4. NOCys (2.5 to 10 microM) or SNP (100 microM) increased the activity of large conductance Ca2+-activated (BK) K' channels in both cell-attached and excised inside-out patches, bathed in either a symmetrical high K+ (130 mM) or an asymmetrically K+ (6 mMout: 130 mMin) physiological saline. Increases in BK channel activity in NOCys (10 microM) or SNP (100 microM) were associated with an increase in the probability of BK channel opening (N.Po), and with a negative shift of the plots of ln(N.Po) against the patch potential, with little change in the slopes of these plots. In cell-attached patches, the increase in N.Po with NOCys was often associated with a decrease in the BK single channel conductance. 5. In both cell-attached and excised patches, NOCys (2.5 to 10 microM) also activated an additional population of channels which allowed inward current flow at potentials positive to EK. In excised inside-out patches bathed in asymmetrical K+ physiological saline, these single channel currents were 2-3 pA in amplitude at -30 mV and reversed in direction near + 10 mV, even if the NaCl (126 mM) concentration in the pipette solution had been replaced with an equimolar concentration of Na gluconate. 6. Under current clamp, NOCys (2.5 microM) and SNP (100 microM) had variable effects on the membrane potential of colonic myocytes, inducing either a small membrane hyperpolarization of5 mV, or a slowly-developing membrane depolarization of about 5 mV. In contrast, NOCys (5 microM) produced a transient membrane hyperpolarization which was followed by a large depolarization of the membrane potential to positive potentials. The electrotonic potentials elicited in response to an injection of constant hyperpolarizing current (10 pA for 400 ms) were little changed during the NOCys (5 PM)-induced membrane hyperpolarization, but significantly reduced (to 61% of control) during the periods of membrane depolarization. 7. It was concluded that NOCys and SNP, directly increased the number of active BK channels in the membrane of colonic myocytes which leads to a small rapidly oscillating membrane hyperpolarization. The following rebound depolarization in NOCys arises from both the direct opening of a population of cationic channels and the blockade of voltage- and Ca-activated K+ conductances. Finally, the apamin-sensitive K+channels underlying the initial transient hyperpolarization recorded in the intact proximal colon, in response to nerve-released or directly-applied NO, have yet to be identified at the single channel or whole-cell current level.

JET was extensively modified in the 1992/93 shutdown. The new pumped divertor and many new systems were brought into operation early in 1994. Operations have progressed to 4MA plasma current and, with substantial additional heating, H-mode confinement results confirm the expected scaling. The high power handling capability of the pumped divertor with sweeping is estimated at 20MW for 20s. H-mode plasmas have large Type I ELMs. With lower hybrid heating alone, 2MA full current drive has been achieved with good efficiency, with ICRF power, effective heating and direct electron heating have been demonstrated.

The dexamethasone suppression test was carried out on 44 children to assess agreement with diagnosis of depression. No significant association was found between suppression of plasma cortisol and depression diagnosed clinically or by cluster analysis.

In this study we examined the effects of insulin on protein kinase C (PKC) activity in cultured fetal chick neurons. PKC activity, measured as 32P incorporation into histone H1 in the presence of calcium (500 microM), phosphatidylserine (100 micrograms/ml), and diolein (3.3 micrograms/ml) minus the incorporation in the presence of calcium alone, was detected in neuronal cytosolic (207 +/- 33 pmol/min/mg) and membrane (33 +/- 8 pmol/min/mg) fractions. Insulin added to intact neurons increased the activity of PKC in both cytosolic and membrane fractions by about 40%. Neurons preincubated with cycloheximide (10 micrograms/ml) 30 min prior to insulin treatment showed the same degree of stimulation of PKC activity by insulin. The activation of PKC was maximal within 5-10 min of insulin exposure and was sustained for at least 60 min. Insulin stimulated PKC in a dose-dependent manner, with a maximal response obtained at 100 ng/ml. Addition of phosphatidylserine and diolein to neuronal cell extracts resulted in the phosphorylation of four major cytosolic proteins (70, 57, 18, and 16 kDa) and one major membrane protein (75 kDa). Phosphorylation of all five proteins was increased 2-fold in extracts from insulin-treated neurons. Immunoblot analysis of whole cell extracts using antibodies against PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon revealed that cultured fetal chick neurons contained only one of these PKC isoforms, the epsilon-isoform. The enzyme was mostly cytosolic. Insulin had no effect on either the amount of distribution of PKC-epsilon in cultured neurons but induced a small change in the mobility of PKC-epsilon on sodium dodecyl sulfate-polyacrylamide gels. When assay conditions were designed to measure specifically the activity of PKC-epsilon, using a synthetic peptide substrate in the absence of calcium, activity was 50 +/- 12% higher in insulin-treated cells (p less than 0.005). PKC activity in control and insulin treated-neurons was almost completely inhibited when assays included a peptide identical to the pseudo-substrate binding site of PKC-epsilon. We conclude that PKC-epsilon is the major PKC isoform present in cultured fetal chick neurons. Insulin stimulates PKC-epsilon activity by a mechanism that does not involve translocation of the enzyme from cytosol to membrane.

We describe the addition of a simple, low-cost 0.9 T fixed magnetic field to a commercially available, variable-temperature sample environment suitable for optical microscopy. The magnetic field is achieved with the use of Fe-Nd-B rare-earth permanent magnets and steel yoke assembly, packaged into a Linkam Scientific Instruments model THMS600 heating and cooling stage. We demonstrate its effectiveness with examples of magnetic ordering of a lipid/water system doped with paramagnetic Tm3+ ions in the presence and absence of the applied magnetic field and at different temperatures.

We describe a variable temperature, relative humidity (0%–100% RH), and bulk liquid neutron reflectometry sample cell suitable for the study of polymeric and biomimetic materials (e.g., lipid bilayers). Compared to previous reflectometry cells, one of the advantages of the present sample environment is that it can accommodate ovens capable of handling either vapor or bulk liquid hydration media. Moreover, the design of the sample cell is such that temperature gradients are minimal over a large area (∼80cm2) allowing for the nontrivial 100% RH condition to be attained. This permits the study, by neutron reflectometry, of samples that are intrinsically unstable in bulk water conditions, and is demonstrated by the lamellar repeat spacing of lipid bilayers at 100% RH being indistinguishable from those same bilayers hydrated in liquid water.

The hormonal and metabolic effects of the somatostatin analogue SMS 201-995 have been examined in normal and diabetic humans. When 50 micrograms of analogue was administered subcutaneously at 8 A.M. and 5:30 P.M., growth hormone secretion over 24 hours was not significantly affected, and the nocturnal growth hormone surge persisted in normal subjects and in type II diabetic patients. Insulin secretion was suppressed in both groups, but glucose tolerance deteriorated only in the normal subjects. Gastrointestinal side effects developed in both groups. Subcutaneous administration of 50 micrograms of SMS 201-995 at 11 P.M. decreased nocturnal growth hormone secretion (peak, 5 +/- 2 milliunits/liter versus 23 +/- 6 milliunits/liter; p less than 0.01) in normal subjects. Postprandial circulating glucose and insulin levels the following day were unaffected by SMS 201-995, and no side effects were observed. In type I diabetic patients receiving a variable rate insulin infusion overnight to maintain normoglycemia, SMS 201-995 (50 micrograms) administered at 11 P.M. decreased insulin requirements for two to three hours after injection. Insulin sensitivity thereafter was unaffected despite suppression of growth hormone secretion. Alternative dosage regimens are necessary to suppress growth hormone release over 24 hours and to minimize side effects in type II diabetes. Administration of the analogue in the late evening suppresses growth hormone secretion overnight, but the "dawn phenomenon" persists in type I diabetic patients.

Changes in thyroid hormone concentration and distribution and plasma cortisol levels have been followed in 11 patients undergoing elective cholocystectomy. A significant rise in total and free thyroxine (T4) and fall in total and free triiodothyronine (T3) were noted after surgery. Reverse T3 concentrations rose substantially, suggesting that peripheral conversion of T4 to T3 is diminished and that there is preferential formation of reverse T3. Serum thyroid stimulating hormone concentrations did not change. There was no direct correlation between the change in cortisol and the change in thyroid hormone or reverse T3 concentrations.

Eight patients who had received megavoltage therapy for Cushing's disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushing's disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow mega-voltage therapy and these may progress to overt hypopituitarism.

Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone greater than 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean +/- SEM prolactin, 288 +/- 36 mU/l, patients, n = 7; 291 +/- 21 mU/l, controls, n = 9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 micrograms (at 20 min, 2417 +/- 658 mU/l, patients, n = 7; 2113 +/- 424 mU/l, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 +/- 536 mU/l, patients, n = 7; 5858 +/- 460 mU/l, controls, n = 8) and insulin-induced hypoglycaemia (at 60 min, 1441 +/- 551 mU/l, patients, n = 7; 1298 +/- 183 mU/l, controls, n = 7) were similar in patients and controls. Two different radioimmunoassays using two different antisera gave similar estimates of serum prolactin levels and prolactin bioactivity in serum was normal in an in-vitro bioassay based on the ability of prolactin to stimulate proliferation of Nb2 node rat lymphoma cells (basal bioassayable prolactin, patients 355 +/- 43 mU/l, n = 10; controls 348 +/- 64 mU/l, n = 7). Metabolic abnormalities similar to those previously noted in hyperprolactinaemia were observed in the patients' 24 h profiles. These included mild hyperglycaemia (24 h mean +/- SEM glucose, 5.47 +/- 0.08 mmol/l, patients; 5.05 +/- 0.14 mmol/l, controls; P less than 0.05) and elevations in circulating lactate, pyruvate and alanine. Blood glycerol was decreased (24 h mean +/- SEM, 0.044 +/- 0.004 versus 0.058 +/- 0.004 mmol/l, P less than 0.05). In the majority of patients with idiopathic galactorrhoea, prolactin concentrations, regulation of secretion and bioactivity in vitro are normal. The galactorrhoea and metabolic abnormalities suggest increased tissue sensitivity to the lactogenic and metabolic actions of prolactin, while ovarian cyclical function is relatively spared.

An alteration of the hypothalamic dopaminergic regulation of LH secretion has been implicated in the abnormal LH secretion of polycystic ovarian syndrome (PCOS). To investigate this, the acute effect of dopamine (DA) receptor blockade on LH, FSH, PRL and TSH secretion was determined. No effect was observed on either LH or FSH secretion in the PCOS patients or in normal women and LH pulsatility appeared to be maintained. When the PCOS patients were divided into those who ovulated in the preceding cycle and those who were anovulatory, it was observed that the ovulatory patients had a normal PRL and TSH response; whereas in the anovulatory patients, the PRL rise was blunted and the TSH response was absent. We conclude that this study gives no evidence to support the hypothesis of altered hypothalamic DA regulation of LH secretion in PCOS. The lack of LH response to DA blockade suggests that a physiological role of DA in the control of LH secretion seems unlikely as determined under these experimental conditions. The differences in PRL and TRH response may reflect anovulation rather than a fundamental abnormality in PCOS.

Ten endocrinologically normal men with secondary sexual impotence were given 500 microng LHRH subcutaneously every 8 h. After 4 weeks treatment the LH response to 500 microng LHRH was reduced from a peak of 35.7+/-5.2 to 16.8+/-3.5 mu/ml (P less than 0.01) and the FSH response from 4.2+/-0.93 to 2.39+/-0.4 mu/ml (P greater than 0.01). Circulating total testosterone, oestradiol, prolactin and sex hormone binding globulin showed no significant changes. Whether this inability of the pituitary to maintain it s response to LHRH is peculiar to impotent men requires further study.

The long-term sequelae of external pituitary irradiation alone or in combination with surgery and/or bromocriptine therapy have been studied in 14 patients with large prolactinomas over an observation period of 6-22 years (mean 13 years). Galactorrhoea was abolished in four of the five females with this symptom, but menstrual disturbance persisted in five of six patients. Sexual function was normal without sex hormone replacement in only one of the eight males after treatment. Neurological deficits were abolished or improved by treatment in all 9 patients with this presentation. Serum prolactin levels declined after treatment (P less than 0.001) and fell to within the normal range off bromocriptine therapy in six of the 14 patients at a mean of 9 years (range 5-17 years) after radiotherapy. All patients had anterior pituitary deficiency of some degree at reassessment, and 13 required replacement treatment. Serial skull radiographs revealed remineralization of the fossa floor in five patients and a decrease in fossa size in three. All five patients who did not also have surgery had evidence of tumour shrinkage without bromocriptine treatment (on CT scan or metrizamide cisternography). Fourth generation CT scans on completion of the study revealed a decrease in tumour mass in all patients, with varying degrees of empty sella in 13 and a cystic intrasellar tumour in the remaining one. Residual tumour was demonstrated in 10 patients, three of whom had normal serum prolactin levels, while one patient without visible tumour had persistent hyperprolactinaemia. Radiotherapy, alone or in combination with surgery and bromocriptine, effectively decreases prolactin secretion and tumour size in patients with large prolactinomas at the expense of other anterior pituitary function. Circulating prolactin levels are a poor marker of residual tumour volume.

The role of serotonin in the prolactin, growth hormone, ACTH and cortisol responses to hypoglycaemia has been investigated in normal subjects using a selective serotonin (5HT2) receptor antagonist, ketanserin. Circulating concentrations of these hormones were measured after administration of insulin (0.1 units/kg body weight iv) to eight normal male subjects with and without simultaneous iv ketanserin (10 mg). Plasma glucose fell to less than 2.0 mmol/1 in all subjects and was unaffected by ketanserin. Ketanserin induced a 50% decrease in the serum prolactin response to hypoglycaemia, 45 and 60 min after administration of insulin (increase in serum prolactin at 60 min: 1145 +/- 295 mU/l without ketanserin; 558 +/- 176 mU/l with ketanserin, P less than 0.05). The peak ACTH response was reduced by 30% (95.3 +/- 33.6 ng/l without ketanserin; 60.0 +/- 22.9 ng/l with ketanserin, P less than 0.05) but the plasma cortisol response was not significantly altered. The serum growth hormone response was unaffected by serotonin blockade. These findings suggest that serotonin, probably acting through 5HT2 receptors, is involved in the stimulation of prolactin and ACTH release but not in the release of growth hormone, during insulin induced hypoglycaemia.