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Biomedical subjects

A P Young

Publications and source records attributed to A P Young.

At least 19 recordsLinked to original sources
PubMed2005

Defect energy of infinite-component vector spin glasses.

We compute numerically the zero-temperature defect energy DeltaE of the vector spin glass in the limit of an infinite number of spin components m , for a range of dimensions 2< or d < or =5 . Fitting to DeltaE approximately L(theta) , where L is the system size, we obtain: theta similar to-1.54 (d=2) , theta similar to-1.04 (d=3) , theta similar to -0.67 (d=4) , and theta similar to -0.37 (d=5) . These results show that the lower critical dimension dl (the dimension where theta changes sign) is significantly higher for m=infinity than for finite m (where 2< dl <3 ).

Journal Article↗
PubMed2005

Spin glasses in the limit of an infinite number of spin components.

We consider spin glass models in which the number of spin components m is infinite. In the formulation of the problem appropriate for numerical calculations proposed by several authors, we show that the order parameter defined by the long-distance limit of the correlation functions is actually zero and there is only "quasi-long-range order" below the transition temperature. Nonetheless, there can be a finite temperature phase transition where the decay of correlations changes from exponential to power law. We also show that the spin glass transition temperature is zero in three dimensions so power-law behavior only occurs at T=0 in this case. We also argue that the order of limits, m-->infinity and N-->infinity is important, where N is the number of spins.

Journal Article↗
PubMed2005

Phase transition in vector spin glasses.

We first give an experimental and theoretical introduction to spin glasses, and then discuss the nature of the phase transition in spin glasses with vector spins. Results of Monte Carlo simulations of the Heisenberg spin glass model in three dimensions are presented. A finite size scaling analysis of the correlation length of the spins and chiralities shows that there is a single, finite-temperature transition at which both spins and chiralities order.

Glass↗
PubMed2004

Absence of an Almeida-Thouless line in three-dimensional spin glasses.

We present results of Monte Carlo simulations of the three-dimensional Edwards-Anderson Ising spin glass in the presence of a (random) field. A finite-size scaling analysis of the correlation length shows no indication of a transition, in contrast with the zero-field case. This suggests that there is no Almeida-Thouless line for short-range Ising spin glasses.

Journal Article↗
PubMed2004

Lack of ultrametricity in the low-temperature phase of three-dimensional Ising spin glasses.

We study the low-temperature spin-glass phases of the Sherrington-Kirkpatrick (SK) model and of the 3-dimensional short-range Ising spin-glass (3DISG). By using clustering to focus on the relevant parts of phase space and reduce finite size effects, we found that for the SK model ultrametricity becomes clearer as the system size increases, while for the short-range case our results indicate the opposite, i.e., lack of ultrametricity. Another method, which does not rely on clustering, indicates that the mean-field solution works for the SK model but does not apply in detail to the 3DISG, for which stochastic stability is also violated.

Journal Article↗
PubMed2003

Interface energies in ising spin glasses.

The replica method has been used to calculate the interface free energy associated with the change from periodic to antiperiodic boundary conditions in finite-dimensional spin glasses. At mean-field level the interface free energy vanishes, but after allowing for fluctuation effects, a nonzero interface free energy is obtained which is significantly different from numerical expectations.

Journal Article↗
PubMed2001

Convergence of Monte Carlo simulations to equilibrium.

We give two direct, elementary proofs that a Monte Carlo simulation converges to equilibrium provided that appropriate conditions are satisfied. The first proof requires detailed balance while the second is quite general.

Journal Article↗
PubMed2001

Therapeutic implications of human endothelial nitric oxide synthase gene polymorphism.

Vascular endothelial dysfunction is now recognized as a common phenomenon in an array of cardiovascular disorders. Production of nitric oxide via the endothelial isoform of nitric oxide synthase [eNOS (previously termed NOS3 or ecNOS)] is vital for a healthy endothelium; several polymorphic variations of the gene encoding eNOS (NOS3) are now known and have been investigated with respect to disease risk. Surprisingly, only approximately half of these studies have demonstrated significant associations between NOS3 polymorphisms and cardiovascular disease, and many reports are contradictory. Central issues include adequate statistical power, appropriateness of control cohorts, multigene interactions and plausible biological consequences. So far, the inconsistencies are not unique to the NOS3 polymorphisms, but probably represent the broad challenges in defining genetic aspects of complex disease processes.

Arginine↗
PubMed2000

Nature of the spin glass state.

The nature of the spin glass state is investigated by studying changes to the ground state when a weak perturbation is applied to the bulk of the system. We consider short range models in three and four dimensions and the infinite range Sherrington-Kirkpatrick (SK) and Viana-Bray models. Our results for the SK and Viana-Bray models agree with the replica symmetry breaking picture. The data for the short range models fit naturally a picture in which there are large scale excitations which cost a finite energy but whose surface has a fractal dimension, d(s), less than the space dimension d. We also discuss the possible crossover to other behavior at larger length scales than the sizes studied.

Journal Article↗
PubMed2000

The 5'2 promoter of the neuronal nitric oxide synthase dual promoter complex mediates inducibility by nerve growth factor.

Neuronal nitric oxide synthase (nNOS) is induced by nerve growth factor (NGF) in pheochromocytoma PC12 cells. Previous studies from our laboratory identified two closely linked promoters (designated 5'1 and 5'2) that mediate transcription of the human nNOS gene in the brain [J. Xie, P. Roddy, T.K. Rife, F. Murad, A.P. Young, Two closely linked but separable promoters for human neuronal nitric oxide synthase gene transcription, Proc. Natl. Acad. Sci. U. S. A. 92 (1995) 1242-1246]. In this report, we demonstrate that luciferase fusion genes under transcriptional control by the 5'1 and 5'2 dual promoter complex are inducible by NGF in stably transformed PC12 cells. In sharp contrast, neither epidermal growth factor (EGF) nor fibroblast growth factor 2 (FGF2) are able to significantly enhance the expression of NOS-luciferase fusion genes. Deletion studies indicate that the 5'2 promoter plays a major role in mediating NGF inducibility. The 5'2 promoter contains six potential Ets binding sites as well as four potential AP1 binding sites. Thus, it is possible that activation of Ets and/or AP1 transcription factors by the Ras-Raf-MAP kinase cascade contributes to the NGF-mediated induction of nNOS.

Animals↗
PubMed1999

The bed crisis of winter 1995-1996 in the British NHS: an illustration of accountability issues.

The aim of this article is to explore the practical complexity of accountability in health care by focusing on a particular crisis affecting one NHS trust in the UK, that of insufficient beds to meet demand. It is presented through the eyes of five middle managers with nursing backgrounds. Although the focus is on their words, their expressions of distress and their awareness of conflict, these lead to a commentary highlighting some of the relationships between theory and practice, policy making and implementation, and, in the final analysis, compulsion and choice. The managers seemed to work within four main patterns of provider accountability: public, professional, pecuniary and personal. These four Ps of accountability created incompatibilities in the accountability process, but the conclusion attempts to draw the threads together to suggest a possible way forward. In order to protect confidentiality, pseudonyms are used for the NHS trust and the interviewees, and some personal details have been disguised.

Attitude of Health Personnel↗
PubMed1997

Steroid hormone receptors activate transcription in glial cells of intact retina but not in primary cultures of retinal glial cells.

We have compared the steroid responsiveness of Müller glial cells of intact embryonic chicken retina with that of primary cultures derived from Müller glia. Appropriately constructed fusion genes were found to be highly glucocorticoid inducible after their cotransfection with an expression vector encoding the human glucocorticoid receptor (GR) into intact embryonic d-10 (E10) or E5.5 retina. Dramatically attenuated inductions were obtained after contransfection of Müller cell primary cultures. The progesterone receptor (PR) was also demonstrated to function in intact retina, but not in Müller cell primary cultures. An immunochemical assay was utilized to confirm that a glucocorticoid-responsive, beta-galactosidase-encoding fusion gene was specifically induced in Müller cells after its transfection into intact retina. Thus, in contrast to Müller cells in intact retina, Müller cells in primary culture have lost the capacity to achieve transcriptional activation by steroid receptors. We postulate that coordinate expression of the GR, and other more general factors required for steroid inducibility, is lost by dispersion and primary culture of retinal Müller glial cells.

Animals↗
PubMed1997

Competing ideologies in health care: a personal perspective.

With the introduction of general management and then of planned markets into the National Health Service (NHS), health care in the UK has gone through a massive amount of change. The effect on those working for the NHS has been 'challenging' and often confusing. This paper aims to clarify what is happening by taking an ideological perspective: what ideologies exist, how they are changing and the strategies being used to ensure their survival. Ideologies are basically about power. The relationship between market, managerial and professional ideologies is analysed using charters, codes of conduct and other associated documents. A tentative conclusion is reached that professional ideologies are able to adjust to the overriding market/consumerist ideology. However, the managerial ideology is having difficulty in gaining any real ground against the professional ideology and is having to move strategically by using audit, not just of finance, but also of clinical judgement, to gain power.

Capitalism↗
PubMed1996

Differential regulation of the two neuronal nitric-oxide synthase gene promoters by the Oct-2 transcription factor.

The Oct-2 transcription factor has been shown previously to repress both the cellular tyrosine hydroxylase and the herpes simplex virus immediate-early genes in neuronal cells. Here we identify the gene encoding the neuronal nitric-oxide synthase (nNOS) as the first example of a gene activated in neuronal cells by Oct-2. The levels of the nNOS mRNA and protein are greatly reduced in neuronal cell lines in which Oct-2 levels have been reduced by an antisense method, although these cells have enhanced levels of tyrosine hydroxylase. Moreover, the nNOS gene regulatory region is activated by Oct-2 expression vectors upon cotransfection into both neuronal and non-neuronal cells, and this response is dependent upon a 20-amino acid region within the COOH-terminal activation domain of Oct-2. Of the two closely linked promoters that drive nNOS gene expression, only the downstream 5.1 promoter is activated by Oct-2, whereas the 5.2 promoter is unaffected. These effects are discussed in terms of the potential role of Oct-2 in regulating nNOS expression in the nervous system.

Animals↗
PubMed1996

DNA and RNA oligomer sequences from the 3' noncoding region of the chicken glutamine synthetase gene from intramolecular hairpins.

The DNA sequence of the chicken glutamine synthetase gene contains an A.T-rich stretch of approximately 1500 base pairs in the 3' noncoding regions of exon 7 [Pu, H., & Young, A. P. (1989) Gene 18, 169-175]. Within this region several palindromic sequences occur that could conceivably form intramolecular structures. One such perfect inverted repeat sequence resides between positions 2605 and 2623. To investigate the hairpin-forming potential for this sequence, optical and calorimetric melting and gel electrophoresis studies have been performed on the following synthetically prepared DNA and RNA oligomer subsequences: DNA, 5'd-T-T-T-T-T-T-A-A-T-A-A-T-T-A-A-A-A-A-A-3'; and RNA, 5'r-U-U-U-U-U-U-A-A-U-A-A-U-U-A-A-A-A-A-A-3'. The DNA strand corresponds to the coding strand sequence while the RNA strand represents the transcribed mRNA. Results of melting analysis of these 19-base, partially self-complementary strands performed in 115 mM Na+ yielded evaluations of their thermodynamic transition parameters. These values are consistent with the melting of unimolecular structures, presumably hairpins. Thermodynamic parameters evaluated by analysis of the optical melting transitions assuming a two-state model and measured directly by differential scanning calorimetry agreed within experimental error. Therefore, melting behavior of the hairpins is all-or-none like. The DNA hairpin is slightly more stable than the RNA hairpin with melting enthalpy delta H0 = 41.2 +/- 3.8 kcal/mol and entropy delta S0 = 133 +/- 11 cal/K.mol (eu) compared to delta H0 = 32.0 +/- 6.0 kcal/mol and entropy delta S0 = 105 +/- 20 eu for the RNA. Gel electrophoretic analysis of these oligomers alone and in various mixtures with their DNA and RNA complementary strands was also performed. Consistent with interpretations of melting results, these experiments revealed both strands alone preferentially form intramolecular hairpin structures. In mixtures in which their complementary strands are in vast molar excess (stoichiometric ratios > 10:1), the intramolecular structures are converted to intermolecular duplexes. For the DNA and RNA strands examined, the conversion is not complete until over a 1000-fold excess of the complementary strand is added. Semiquantitative analysis of gel electrophoretograms enabled evaluations of the relative free energies of the hairpin and duplex states as a function of complementary strand concentration. With the finding that these sequences preferentially form hairpins, potential roles these structures could play in regulatory activities are considered.

Animals↗
PubMed1996

Who sets the business agenda?

Business planning is now a key activity in health care organizations and is affecting the way in which both managers and professionals carry out their work. This paper starts by examining some of the recent changes affecting business planning in a number of health care sectors. It then suggests that the business agenda can be based on four possible models-financial, marketing, needs or power. The evidence is examined, looking at input, output and process information, and some conclusions reached on what, in reality, influences the business agenda, as well as what doesn't, but perhaps should. The overwhelming importance of financial and power features of agenda setting are recognized and the paper concludes by suggesting how the contents of the agenda may be shifted by allowing the voices of a wider group of participants to be heard. Perhaps a new model will be developed based initially on information sharing but moving to real communication between the different perspectives now in existence.

Commerce↗
PubMed1995

Two closely linked but separable promoters for human neuronal nitric oxide synthase gene transcription.

In this report we demonstrate that the human cerebellum contains neuronal nitric oxide synthase (nNOS) mRNAs with two distinct 5'-untranslated regions that are encoded through use of closely linked but separate promoters. nNOS cDNA clones were shown to contain different 5' terminal exons spliced to a common exon 2. Genomic cloning and sequence analysis demonstrate that the unique exons are positioned within 300 bp of each other but separated from exon 2 by an intron that is at least 20 kb in length. A CpG island engulfs the downstream 5'-terminal exon. In contrast, most of the upstream exon resides outside of this CpG island. Interestingly, the upstream exon includes a GT dinucleotide repeat. A fusion gene with a 414-bp nNOS genomic fragment that includes a portion of the upstream 5'-terminal exon and its immediate 5'-flanking DNA is expressed in transfected HeLa cells. Also expressed is a fusion gene that contains the luciferase reporter under transcriptional control by a 308-bp genomic fragment that includes the region separating both 5'-terminal exons. These results indicate that expression of these exons is subject to transcriptional control by separate promoters. However, the proximity of these promoters raise the possibility that complex interactions may be involved in regulating nNOS gene expression at these sites.

Amino Acid Oxidoreductases↗