Calcium(II)3 (3,5-Diisopropylsalicylate)6(H2O)6 Activates Nitric Oxide Synthase: An Accounting for its Action in Decreasing Platelet Aggregation

Purposes of these studies were first; to determine whether or not Calcium(II)3 (3,5- diisopropylsalicylate)6(H2O)6 [Ca(II)3(3,5-DIPS)6], a lipophilic calcium complex, could decrease activated-platelet aggregation, and second; to determine whether or not it is plausible that Ca(II)3(3,5-DIPS)6 decreases activated-platelet aggregation by facilitating the synthesis of Nitric Oxide (NO) by Nitric Oxide Synthase (NOS). The influence of Ca(II)3(3,5-DIPS)6 on the initial rate of activated-platelet aggregation was determined by measuring the decrease in rate of increase in transmission at 550 nm for a suspension of Thrombin-CaCl2 activated platelets following the addition of 0, 50, 100, 250, or 500 μM Ca(II)3(3,5-DIPS)6. To establish that the Ca(lI)3(3,5- DIPS)6-mediated decrease in aggregation was due to activation of NOS, the effect of ʟ-NMMA, an inhibitor of NOS, on the inhibition of platelet aggregation by Ca(II)3(3,5-DIPS)6 was determined using a suspension of activated platelets contaimng 0 or 250 μM Ca(II)3(3,5-DIPS)6 without or with 1 mM ʟ-NMMA. An in vitro Bovine Brain NOS reaction mixture, containing CaCl2 for the activation of Phosphodiesterase-3' ,5'-Cyclic Nucleotide Activator required for the activation of NOS, was used to determine whether or not Ca(II)3(3,5-DIPS)6 could be used as a substitute for the addition of Ca. The decrease in absorbance at 340 nm, lambda maximum for NADPH, was measured to determine NOS activity following the addition of NOS to the complete reaction mixture containing either CaCl2, Ca(II)3(3,5-DIPS)6, or neither Ca compound. Increasing the concentration of Ca(II)3(3,5-DIPS)6 caused a concentration related decrease in activated platelet aggregation. The addition of ʟ-NMMA to activated platelets, in the absence of Ca(II)3(3,5-DIPS)6, caused a 129% increase in initial rate of platelet aggregation. The initial rate of platelet aggregation decreased 74% with the addition of 250 μM Ca(II)3(3,5-DIPS)6 and the addition of ʟ-NMMA plus 250 μM Ca(II)3(3,5-DIPS)6 caused a 197% decrease in initial rate of aggregation compared to the initial rate observed width the presence of 1 mM ʟ-NMMA alone. There was only a small, 27%, increase in initial rate of 0.4 mM NADPH oxidation when 0.9 mM CaCl2 was added to the NOS reaction mixture in comparison to the initial rate of NADPH oxidation with no addition of CaCI2. Addition of an equivalent amount of Ca in the form of Ca(II)3(3,5-DIPS)6, 333 μM, caused a 37% increase in initial rate of NADPH oxidation compared to the addition of 0.9 mM CaCl2. Addition of increasing concentrations of ʟ-NMMA plus 0.9 mM CaCl2 or 333 μM Ca(II)3(3,5-DIPS)6 to the NOS reaction mixture caused a concentration related increase in initial rate of NADPH oxidation. Addition of ʟ-NMMA while expected to decrease NADPH oxidation actually increased the rate of NADPH oxidation. Additions of 133 μM or 267 μM Ca(II)3(3,5- DIPS)6 also caused concentration related increases in initial rate of NADPH oxidation in the presence of 113 μM ʟ-NMMA. However, the addition of 533 μM Ca(II)3(3,5-DIPS)6 caused a dramatic decrease in initial rate of NADPH oxidation by NOS. It is concluded that: 1) Ca(II)3(3,5- DIPS)6 activates platelet NOS in preventing platelet aggregation, 2) in vitro NOS activity can be observed spectrophotometrically by following the consumption of NADPH as a decrease in absorbance at 340 nm, 3) Ca(II)3(3,5-DIPS)6 plays a role in enhancing Bovine Brain NOS activity resulting in an increased rate of NADPH oxidation by NOS, 4) Ca(II)3(3,5-DIPS)6 is a useful form of Ca in activating NOS and superior to CaCl2 with regard to the facilitation of a NADPH oxidation, and 5) ʟ-NMMA stimulates Bovine Brain NOS activity rather than causing an inhibition of this enzyme and must serve as a reducible substrate for Bovine Brain NOS

Clients' interpretation of risks provided in genetic counseling.

Clients in 544 genetic counseling sessions who were given numeric risks of having a child with a birth defect between 0% and 50% were asked to interpret these numeric risks on a five-point scale, ranging from very low to very high. Whereas clients' modal interpretation varied directly with numeric risks between 0% and 15%, the modal category of client risk interpretation remained "moderate" at risks between 15% and 50%. Uncertainty about normalcy of the next child increased as numeric risk increased, and few clients were willing to indicate that the child would probably or definitely be affected regardless of the numeric risk. Characteristics associated with clients' "pessimistic" interpretations of risk, identified by stepwise linear regression, included increased numeric risk, discussion in depth during the counseling session of whether they would have a child, have a living affected child, discussion of the effects of an affected child on relationships with client's other children, and seriousness of the disorder in question (causes intellectual impairment). Client interpretations are discussed in terms of recent developments in cognitive theory, including heuristics that influence judgments about risks, and implications for genetic counseling

Dynamic optical lattices: two-dimensional rotating and accordion lattices for ultracold atoms

We demonstrate a novel experimental arrangement which rotates a 2D optical lattice at frequencies up to several kilohertz. Ultracold atoms in such a rotating lattice can be used for the direct quantum simulation of strongly correlated systems under large effective magnetic fields, allowing investigation of phenomena such as the fractional quantum Hall effect. Our arrangement also allows the periodicity of a 2D optical lattice to be varied dynamically, producing a 2D accordion lattice.Comment: 7 pages, 5 figures, final versio

Investigating what works to support family carers of people with dementia: a rapid realist review

Introduction - Advances in longevity and medicine mean that many more people in the UK survive life-threatening diseases but are instead susceptible to life-limiting diseases such as dementia. Within the next 10 years those affected by dementia in the UK is set to rise to over 1 million, making reliance on family care of people with dementia (PWD) essential. A central challenge is how to improve family carer support to offset the demands made by dementia care which can jeopardise carers’ own health. This review investigates ‘what works to support family carers of PWD’. Methods - Rapid realist review of a comprehensive range of databases. Results - Five key themes emerged: (1) extending social assets, (2) strengthening key psychological resources, (3) maintaining physical health status, (4) safeguarding quality of life and (5) ensuring timely availability of key external resources. It is hypothesized that these five factors combine and interact to provide critical biopsychosocial and service support that bolsters carer ‘resilience’ and supports the maintenance and sustenance of family care of PWD. Conclusions - ‘Resilience-building’ is central to ‘what works to support family carers of PWD’. The resulting model and Programme Theories respond to the burgeoning need for a coherent approach to carer support

'Mindless markers of the nation': The routine flagging of nationhood across the visual environment

The visual environment has increasingly been used as a lens with which to understand wider processes of social and economic change with studies employing in-depth qualitative approaches to focus on, for example, gentrification or trans-national networks. This exploratory paper offers an alternative perspective by using a novel method, quantitative photo mapping, to examine the extent to which a particular socio-cultural marker, the nation, is ‘flagged’ across three contrasting sites in Britain. As a multi-national state with an increasingly diverse population, Britain offers a particularly fruitful case study, drawing in debates around devolution, European integration and Commonwealth migration. In contributing to wider debates around banal nationalism, the paper notes the extent to which nations are increasingly articulated through commerce, consumption and market exchange and the overall significance of everyday markers (signs, objects, infrastructure) in naturalising a national view of the world

Students as co-creators of teaching approaches, course design and curricula: implications for academic developers

Within higher education, students’ voices are frequently overlooked in the design of teaching approaches, courses and curricula. In this paper we outline the theoretical background to arguments for including students as partners in pedagogical planning processes. We present examples where students have worked collaboratively in design processes along with the beneficial outcomes of these examples. Finally we focus on some of the implications and opportunities for academic developers of proposing collaborative approaches to pedagogical planning

Does coevolution promote species richness in parasitic cuckoos?

Why some lineages have diversified into larger numbers of species than others is a fundamental but still relatively poorly understood aspect of the evolutionary process. Coevolution has been recognized as a potentially important engine of speciation, but has rarely been tested in a comparative framework. We use a comparative approach based on a complete phylogeny of all living cuckoos to test whether parasite–host coevolution is associated with patterns of cuckoo species richness. There are no clear differences between parental and parasitic cuckoos in the number of species per genus. However, a cladogenesis test shows that brood parasitism is associated with both significantly higher speciation and extinction rates. Furthermore, subspecies diversification rate estimates were over twice as high in parasitic cuckoos as in parental cuckoos. Among parasitic cuckoos, there is marked variation in the severity of the detrimental effects on host fitness; chicks of some cuckoo species are raised alongside the young of the host and others are more virulent, with the cuckoo chick ejecting or killing the eggs/young of the host. We show that cuckoos with a more virulent parasitic strategy have more recognized subspecies. In addition, cuckoo species with more recognized subspecies have more hosts. These results hold after controlling for confounding geographical effects such as range size and isolation in archipelagos. Although the power of our analyses is limited by the fact that brood parasitism evolved independently only three times in cuckoos, our results suggest that coevolutionary arms races with hosts have contributed to higher speciation and extinction rates in parasitic cuckoos

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

Connexin 43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43(ΔCT/fl)) were studied. Cx43(ΔCT/fl) mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43(fl/fl) controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43(ΔCT) is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43(ΔCT) mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43(ΔCT) were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions

The Pseudosquares Prime Sieve

We present the pseudosquares prime sieve, which finds all primes up to n

SWIFT Code Assessment for Two Similar Transonic Compressors

One goal of the NASA Fundamental Aeronautics Program is the assessment of computational fluid dynamic (CFD) codes used for the design and analysis of many aerospace systems. This paper describes the assessment of the SWIFT turbomachinery analysis code for two similar transonic compressors, NASA rotor 37 and stage 35. The two rotors have identical blade profiles on the front, transonic half of the blade but rotor 37 has more camber aft of the shock. Thus the two rotors have the same shock structure and choking flow but rotor 37 produces a higher pressure ratio. The two compressors and experimental data are described here briefly. Rotor 37 was also used for test cases organized by ASME, IGTI, and AGARD in 1994-1998. Most of the participating codes over predicted pressure and temperature ratios, and failed to predict certain features of the downstream flowfield. Since then the AUSM+ upwind scheme and the k- turbulence model have been added to SWIFT. In this work the new capabilities were assessed for the two compressors. Comparisons were made with overall performance maps and spanwise profiles of several aerodynamic parameters. The results for rotor 37 were in much better agreement with the experimental data than the original blind test case results although there were still some discrepancies. The results for stage 35 were in very good agreement with the data. The results for rotor 37 were very sensitive to turbulence model parameters but the results for stage 35 were not. Comparison of the rotor solutions showed that the main difference between the two rotors was not blade camber as expected, but shock/boundary layer interaction on the casing