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The evolution of the liquid–vapor interface of a Lennard-Jones fluid is examined with molecular dynamics simulations using the intrinsic sampling method. Results suggest clear damping of the intrinsic profiles with increasing temperature. Investigating the surface stress distribution, we have identified a linear variation of the space-filling nature (fractal dimension) of the stress clusters at the intrinsic surface with increasing surface tension or, equivalently, with decreasing temperature. A percolation analysis of these stress networks indicates that the stress field is more disjointed at higher temperatures. This leads to more fragile (or poorly connected) interfaces which result in a reduction in surface tension.

Background/Objectives:: Iron and phosphate are both vital to many biological cellular processes with central roles in energy metabolism, cellular proliferation and nucleic acid synthesis. Regulatory pathways in some of these metabolic pathways may intersect at fibroblast growth factor 23 (FGF23), a major phosphate regulatory hormone. Iron is reported to induce hypophosphataemia in rare cases, and recent reports suggest that iron deficiency may upregulate FGF23 synthesis by mechanisms involving hypoxia-inducible factor 1α (HIF1α). Our objective was to evaluate the effect of administration of intravenous iron polymaltose on intact and c-terminal FGF23 (i:cFGF23) ratios in two independent cohorts of patients, iron-deficient but non-inflamed patients and haemodialysis (HD)-dependent patients, and to examine the balance of synthesis and degradation. Subjects/Methods:: We studied biochemical effects of intravenous iron polymaltose on both iFGF23 and cFGF23 fragments and their ratios in two patient groups: iron-deficient patients with normal renal function (ID-norm) and HD patients receiving iron supplementation (HD-ESKD) at a single institution. Patients were tested at baseline, day 4 and day 12 post iron administration. Results:: Parenteral iron polymaltose resulted in increased i:cFGF23 ratios in ID-norm patients where circulating cFGF23 levels decreased with no appreciable effect on iFGF23, whereas no significant changes in i:cFGF23 ratios were observed in HD-ESKD patients following intravenous administration of 100mg iron polymaltose. Conclusions:: Dysregulation of intracellular FGF23-processing mechanisms may be related to iron deficiency per serather than iron repletion with iron polymaltose. In ID-norm, i:cFGF23 ratios altered with iron administration without significant clinical alterations in mineral parameters, implying that other regulatory mechanisms may be important. Finally, iron supplementation in HD-ESKD patients does not appear to significantly affect i:cFGF23 ratios already disturbed by a chronic inflammatory or functionally iron-deficient state.

It has become well established for several genes that targeting of histone acetylation to promoters is required for the activation of transcription. In contrast, global patterns of acetylation have not been ascribed to any particular regulatory function. In Drosophila, a specific modification of H4, acetylation at lysine 16, is enriched at hundreds of sites on the male X chromosome due to the activity of the male-specific lethal (MSL) dosage compensation complex. Utilizing chromatin immunoprecipitation, we have determined that H4Ac16 is present along the entire length of X-linked genes targeted by the MSL complex with relatively modest levels of acetylation at the promoter regions and high levels in the middle and/or 3' end of the transcription units. We propose that global acetylation by the MSL complex increases the expression of X-linked genes by facilitating transcription elongation rather than by enhancing promoter accessibility. We have also determined that H4Ac16 is absent from a region of the X chromosome that includes a gene known to be dosage-compensated by a MSL-independent mechanism. This study represents the first biochemical interpretation of the very large body of cytological observations on the chromosomal distribution of the MSL complex.

Retinoic acid induces cell differentiation and suppresses cell growth in a wide spectrum of cell lines, and down-regulation of activator protein-1 activity by retinoic acid contributes to these effects. In embryonic stem cell-like F9 teratocarcinoma cells, which are widely used to study retinoic acid actions on gene regulation and early embryonic differentiation, retinoic acid treatment for 4 days resulted in suppression of cell growth and differentiation into primitive and then visceral endoderm-like cells, accompanied by a suppression of serum-induced c-Fos expression. The MAPK (ERK) pathway was involved in mitogenic signaling in F9 cells stimulated with serum. Surprisingly, although c-Fos expression was reduced, the MAPK activity was not decreased by retinoic acid treatment. We found that retinoic acid treatment inhibited the phosphorylation of Elk-1, a target of activated MAPK required for c-Fos transcription. In F9 cells, the MAPK/MEK inhibitor PD98059 suppressed Elk-1 phosphorylation and c-Fos expression, indicating that MAPK activity is required for Elk-1 phosphorylation/activation. Phosphoprotein phosphatase 2B (calcineurin), the major phosphatase for activated Elk-1, is not the target in the disassociation of MAPK activation and c-Fos expression since its inhibition by cyclosporin A or activation by ionomycin had no significant effects on serum-stimulated c-Fos expression and Elk-1 phosphorylation. Thus, we conclude that retinoic acid treatment to induce F9 cell differentiation uncouples Ras/MAPK activation from c-Fos expression by reduction of Elk-1 phosphorylation through a mechanism not involving the activation of phosphoprotein phosphatase 2B.

In Drosophila, dosage compensation-the equalization of most X-linked gene products in males and females-is achieved by a twofold enhancement of the level of transcription of the X chromosome in males relative to each X chromosome in females. A complex consisting of at least five gene products preferentially binds the X chromosome at numerous sites in males and results in a significant increase in the presence of a specific histone isoform, histone 4 acetylated at lysine 16. Recently, RNA transcripts (roX1 and roX2) encoded by two different genes have also been found associated with the X chromosome in males. We have partially purified a complex containing MSL1, -2, and -3, MOF, MLE, and roX2 RNA and demonstrated that it exclusively acetylates H4 at lysine 16 on nucleosomal substrates. These results demonstrate that the MSL complex is responsible for the specific chromatin modification characteristic of the X chromosome in Drosophila males.

The adipocyte fatty acid-binding protein (AFABP) is believed to transfer unesterified fatty acids (FA) to phospholipid membranes via a collisional mechanism that involves ionic interactions between lysine residues on the protein surface and phospholipid headgroups. This hypothesis is derived largely from kinetic analysis of FA transfer from AFABP to membranes. In this study, we examined directly the binding of AFABP to large unilamellar vesicles (LUV) of differing phospholipid compositions. AFABP bound LUV containing either cardiolipin or phosphatidic acid, and the amount of protein bound depended upon the mol % anionic phospholipid. The K(a) for CL or PA in LUV containing 25 mol % of these anionic phospholipids was approximately 2 x 10(3) M(-1). No detectable binding occurred when AFABP was mixed with zwitterionic membranes, nor when acetylated AFABP in which surface lysines had been chemically neutralized was mixed with anionic membranes. The binding of AFABP to acidic membranes depended upon the ionic strength of the incubation buffer: >/=200 mM NaCl reduced protein-lipid complex formation in parallel with a decrease in the rate of FA transfer from AFABP to negatively charged membranes. It was further found that AFABP, but not acetylated AFABP, prevented cytochrome c, a well characterized peripheral membrane protein, from binding to membranes. These results directly demonstrate that AFABP binds to anionic phospholipid membranes and suggest that, although generally described as a cytosolic protein, AFABP may behave as a peripheral membrane protein to help target fatty acids to and/or from intracellular sites of utilization.

Cells in culture often undergo a "burst" of free sphingosine, sphingosine 1-phosphate, ceramide, and other bioactive lipids upon removal of "conditioned" medium, and at least one lipid signaling pathway (protein kinase C) has been shown to be affected by these changes (Smith, E. R. & Merrill A. H., Jr. (1995) J. Biol. Chem. 270, 18749-18758; Smith, E. R., Jones, P. L., Boss, J. M. & Merrill, A. H., Jr. (1997) J. Biol. Chem. 272, 5640-5646). Whereas increases in sphinganine and dihydroceramide are responses to provision of precursors for sphingolipid biosynthesis de novo in the new medium, the sphingosine burst is due to sphingolipid turnover upon removal of suppressive factor(s) in conditioned medium. This study describes the purification and characterization of these suppressive factors. Conditioned medium from J774 cells was fractionated into two components that suppress the burst as follows: ammonium ion, which reaches 2-3 mM within 48 h of cell culture; and a low molecular weight, cationic compound that has been assigned the structure 2, 6-bis(omega-aminobutyl)-3,5-diimino-piperazine (for which we suggest the name "batrachamine" based on its appearance) by (1)H and (13)C NMR, Fourier transform infrared spectroscopy, and mass spectrometric analyses. The physiological significance of these compounds as suppressors of sphingolipid metabolism is unclear; however, ammonium ion is a by-product of amino acid catabolism and reaches high concentrations in some tissues. Batrachamine is even more intriguing because this is, as far as we are aware, the first report of a naturally occurring compound of this structural type. Considering the many cell functions that are affected by sphingoid bases and their derivatives, the effects of NH(4) and batrachamine on sphingolipid metabolism may have important implications for cell regulation.

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We study the interaction energy of a system of N particles with embedded point dipoles in a cube, this cube being duplicated indefinitely throughout space. We are able to evaluate exactly this energy for arbitrary positions and orientations of the N particles, to provide an effective hamiltonian suitable for the study of the statistical mechanics of dipolar systems by both rigorous methods and computer simulation techniques. We describe methods for the rapid numerical evaluation of the hamiltonian and how it may be employed for the tasks outlined above.

Fast moment methods in computational statistical mechanics allow the computation time for a time step of a molecular dynamics algorithm of N charged particles to grow linearly with N. The method is developed and optimized, with timing estimates, for any potential which has a Taylor series about a non-zero interparticle separation. Some examples, are given with a discussion of their errors.

Castration of mice in freerunning conditions (total darkness, DD) causes a reduction of running wheel activity in the beginning of the active period (alpha) and stimulates activity at the end of alpha. Simultaneously, the period (tau) of the freerunning rhythm is increased. Both effects are abolished by implantation of a Silastic capsule from which a physiological dose of testosterone is released at a constant rate. The results are tentatively explained by differential endocrine influences on two oscillating components in the pacemaker of the circadian activity rhythm.

PCAF and hGCN5 are distinct human genes that encode proteins related to the yeast histone acetyltransferase and transcriptional adapter GCN5. The PCAF protein shares extensive similarity with the 439 amino acids of yGCN5, but it has an approximately 350 amino acid N-terminal extension that interacts with the transcriptional co-activator p300/CBP. Adenoviral protein E1a can disrupt PCAF-CBP interactions and prevent PCAF-dependent cellular differentiation. In this report, we describe the cloning and initial characterization of a Drosophila homolog of yGCN5. In addition to the homology to yGCN5, the Drosophila protein shares sequencesimilarity with the N-terminal portion of human PCAF that is involved in binding to CBP. In the course of characterizing dGCN5, we have discovered that hGCN5 also contains an N-terminal extension with significant similarity to PCAF. Interestingly, in the case of the h GCN5 gene, alternative splicing may regulate the production of full-length hGCN5. The presence of the N-terminal domain in a Drosophila GCN5 homolog and both human homologs suggests that it was part of the ancestral form of metazoan GCN5.

Plasma and pituitary concentrations of prolactin (PRL) were determined by radioimmunoassay in younger mature (2–6-month-old) and aged (14–20-month-old) C57BL/6 mice, Chinese hamsters, Syrian hamsters, Mongolian gerbils and Wistar rats. All females exhibited a predominantly leukocytic vaginal smear prior to bleeding. Preliminary tests indicated that PRL in C. hamsters crossreacted to a greater extent with mouse PRL antiserum than with rat PRL antiserum. Gerbil PRL crossreacted with either mouse or rat PRL antisera; however, the parallelism of plasma and pituitary dose-response curves was not statistically identical to standards of either antisera. The assays were conducted using mouse PRL antiserum since gerbil PRL was closest to standard curves of the mouse. PRL levels in the S. hamster were assayed using rat PRL. Circulating plasma levels of PRL were significantly lower (P<0.001) in aged S. hamsters and statistically higher (P<0.001) in senescent rats when compared with those in their younger counterparts. Pituitary levels of PRL were significantly depressed (P<0.001) in aged mice and gerbils compared with levels in younger females. There were no statistical differences in the levels of plasma or pituitary PRL in the two age groups of C. hamsters. These data reflect age-related changes in PRL secretion and emphasize species diversity in the secretion of this hormone among older laboratory rodents.

We consider the grand canonical partition function for the ordered one-dimensional, two-component plasma at fugacity? in an applied electric fieldE with Dirichlet boundary conditions. The system has a phase transition from a low-coupling phase with equally spaced particles to a high-coupling phase with particles clustered into dipolar pairs. An exact expression for the partition function is developed. In zero applied field the zeros in the? plane occupy the imaginary axis from -i8 to -i?c and i?c to i8 for some ?c. They also occupy the diamond shape of four straight lines from ±i?c to ?c and from ±i?c to -?c. The fugacity? acts like a temperature or coupling variable. The symmetry-breaking field is the applied electric fieldE. A finite-size scaling representation for the partition in scaled coupling and scaled electric field is developed. It has standard mean field form. When the scaled coupling is real, the zeros in the scaled field lie on the imaginary axis and pinch the real scaled field axis as the scaled coupling increases. The scaled partition function considered as a function of two complex variables, scaled coupling and scaled field, has zeros on a two-dimensional surface in a domain of four real variables. A numerical discussion of some of the properties of this surface is presented.

To determine whether changes in peripheral vitamin B6 levels are associated with symptoms of premenstrual syndrome (PMS), ten PMS patients and ten controls were studied. They gave blood at 2- or 3-day intervals through three menstrual cycles. The vitamin B6 was measured by fluorometry after the serum was heated with semicarbazide, and luteinizing hormone (LH) was measured by radioimmunoassay. In the controls, vitamin B6 values were 15.3 ± 3.0 μg/dl (mean ± SEM) during the luteal phase, and 14.2 ± 3.0 μg/dl during the follicular phase. No significant changes were noted between the two values. In the patients, the values were 14.7 ± 1.9 μg/dl during the luteal phase which was not significantly different from 15.4 ± 3.3 μg/dl during the follicular phase. No significant changes were noted between the controls and the patients in either the luteal or the follicular phase. Although it remains possible that vitamin B6 deficiency may exist in a subgroup of PMS patients, its deficiency was not demonstrated by peripheral vitamin B6 levels in our study.An zehn Patientinnen mit prämenstruellem Syndrom (PMS) und zehn Kontrollpersonen wurde untersucht, ob ein Zusammenhang zwischen Veränderungen des peripheren Vitamin B6-Spiegels und den bei PMS auftretenden Beschwerden besteht. Im Verlaufe dreier Menstru-arionszyklen wurde den Patientinnen im Abstand von zwei bis drei Tagen Blut abgenommen. Die Bestimmung des Vitamin B6-Gehalts erfolgte mittels Fluorimetrie, nachdem das Serum zusammen mit Semicarbazid erhitzt worden war. Der Gehalt an Luteinisierungshormon (LH) wurde durch Radioimmunoassay ermittelt. Bei den Kontrollpersonen lagen die Vitamin B6-Werte in der Lutealphase bei 15-3 ± 3-0 μg/dl (Mittel ± Standardfehler des Mittels) und in der follikulären Phase bei 14.2 ± 3.0 μg/dl. Es wurden keine signifikanten Veranderungen im Verhältnis der beiden Werte gefunden. Die Patientinnen wicsen in der Lutealphase Werte von 14.7 ± 1.9 μg/dl auf, die sich nicht signifikant von den in der follikulären Phase gemessenen Werten - nämlich 15.4 ± 3.3 μg/dl - unterschieden. Weder in der Luteal- noch in der follikulären Phase wurden im Vergleich zwischen Kontrollpersonen und Patientinnen signifikantc Veränderungen festgestellt. Zwar ist nach wic vor denkbar, daß bei einer Untergruppe von PMS-Patientinnen ein Mangel an Vitamin B6 vorliegt, doch konnte cin solchcr Mangel bei der Messung der peripheren Vitamin B6-Werte im Rahmen unserer Studie nicht nachgewiescn werden.Pour savoir si les changements de nivcaux périphériques de vitamine B6 sont associés aux sympto˘mes du syndrome premenstruel (SPM), les auteurs ont étudié 10 patientes SPM et 10 témoins. Toutes ont subi des prélèvements sanguins à intervalles de 2 ou 3 jours, dans le cadre de 3 cycles menstruels. La vitamine B6 a été mesurée par la fluorimétrie après chauffage du sérum avec du semicarbazide, tandis que l'hormone lutéinisante (LH) a été mesurée par radio-immunodosage. Chez les temoins, les valeurs de la vitamine B6 ont ete de 15.3 ± 3.0 μg/dl (moyenne ± erreur type de la moyenne) pendant la phase lutéale, et 142 ± 3.0 μg/dl pendant la phase folliculaire. Aucun changement appréciable n'a été relevé entre les deux valeurs. Chez les patientes, les valeurs ont été de 14.7 ± 1.9 μg/dl pendant la phase luteale, valeurs assez proches des 15.4 ± 3.3 μg/dl de la phase folliculaire. Aucun changement significatif n'a été relevée entre les temoins et les patientes, ni durant la phase lutéale, ni durant la phase folliculaire. Bien qu'il demeure possible qu'il existe une carence de vitamine B6 dans un sousgroupe de patientes soufFrant du SPM, cette carence n'a pas été démontrée par les niveaux périphériques de vitamine B6 dans le cadre de notre étude.

A geometry for simulation of polar surfaces of ionic crystals is described. The simulation cells form a two-dimensional periodic array with one side bounded by the polar surface of a large piece of rigid ionic crystal. To simulate a polar surface in this way, the surface must carry excess charge to ensure that the cells are a model of the surface of a piece of crystal in bulk thermodynamic equilibrium. The electrostatic energy of the simulation cells is presented as a sum of convergent two dimensional lattice sums. The cancellation of divergences implicit in this energy because of the excess charge distributions is described in detail.

We investigate the effects of a change in external dielectric constant ε' on the properties of a system of charges in periodic boundary conditions. The mean square dipole moment fluctuations of a configuration are shown to depend strongly on ε' in the thermodynamic limit. Simulations of 216 restricted primitive electrolyte particles with ε' = 1 and ε' = ∞ at η = 0·35 and Γ = 2, 5 and 10 are reported and obey the formula for the change in mean square dipole moment fluctuations rather well.

We report molecular dynamics simulations of 64 model ethylene oxide (oxirane) molecules at a mass density of 0·9 g cm-3 and a temperature in the vicinity of 260 K. We obtained a dielectric constant of 12·6 ± 0·05 which compares well with the experimental value of 13·9 at 272·15 K.

A method of solution of the mean spherical approximation (MSA) is given for systems of hard spheres whose interaction potential is of the form [image omitted] outside the hard core. The method thus allows solution of the MSA for a wide range of potentials. Details are given for the cases [image omitted] and [image omitted] +φ2 exp (-μ2r). The method is also used to study the MSA for systems in which the interparticle potential is of the form [image omitted] The difficulties of an exact solution for such systems are pointed out and an approximate method of solution developed. The limit μ →0 is considered. Details are given for the case [image omitted]

The RISM equation for diatomic symmetric molecules is solved using a Weiner-Hopf factorization technique. This procedure introduces a function Q(r) which is related to both the site-site total correlation function h(r) and the site-site direct correlation function c(r). Determining Q(r) effectively solves the RISM equation. We show that Q(r) can be written as an infinite sum, for r greater than the hard sphere diameter R, and using this form, solve for Q(r) when 0 < r < R. To generate a solution, this infinite series must be truncated. A method to determine the coefficients in the truncated series is outlined.

A graphical decomposition theorem is proven which allows an exact summation of the one-particle distribution function ρ1(1). Using the superposition approximation, a monolayer density profile and adsorption isotherm are calculated numerically for krypton at 100 K. The monolayer profile illustrates the structure due to hard-sphere geometrical exclusion in the adsorbate. The adsorption isotherm is compared with one derived using the Percus-Yevick approximation.

We introduce a model hard-sphere solid with correlation functions in excellent agreement with hard-sphere solid correlation functions calculated from simulations. The model solid is of independently distributed Gaussian particles centred at the points of a face-centred cubic lattice. We generalize the model to any lattice and use it to calculate contributions to the internal energy due to long-ranged potentials.

We analyse a simple model for the correlation functions of the hard-sphere solid. The result is in agreement with the parametrization introduced by Weis and Kincaid and Weis. By transforming this result we show singularities in the structure factor which result from the long-range part of g(r).

Summary.Circulating plasma concentrations of LH from young mature (3–4 months old), middle-aged (15–18 months old) and aged (31–32 months old) male C57BL/6 mice, Syrian hamsters (3–4, 19–20 and 24–25 months old), Fischer 344 rats (3–4, 18–19 and 28–29 months old), Chinese hamsters (3–4, 19–20 and 29–30 months old) and Mongolian gerbils (3–4 and 19–22 months old) were analysed using a radioimmunoassay (RIA) and a radioreceptor assay (RRA). Male rats exhibited the greatest changes with advancing age: the oldest rats had an almost undetectable quantity of plasma LH, as measured by both assays. In contrast, the oldest male Syrian hamsters had significantly higher levels of LH than did younger animals. A significant decrease occurred in the amounts of LH detectable by RRA in middle-aged Chinese hamsters which was not evident with the RIA. There were no statistically significant differences in LH levels of C57BL/6 mice and gerbils with increasing age. The mean RRA:RIA ratios indicated that age-related differences in LH concentrations resulted from physiological changes in the secretion or the metabolic clearance of LH and not from changes in the biological potency of LH.

A prospective, two-phase, drug utilization review (DUR) was performed at the Royal Adelaide Hospital (RAH) to determine the extent and pattern of vancomycin use. For all patients commencing oral or parenteral vancomycin, treatment indication, route of administration, duration of therapy, results of culture and sensitivity tests, adverse drug reactions and results of therapeutic drug level monitoring were recorded. Vancomycin courses were classified as being for therapy or prophylaxis and compared with predetermined audit criteria to assess appropriateness of use.

We present a reverse phase liquid chromatographic assay involving pre-column o-phthalaldehyde derivatization and fluorescence detection with the capability of measuring dezocine in human serum and urine for pharmacokinetic or forensic purposes. It features a simple liquid-liquid extraction scheme using hexane, conservative detection limits of 1 ng/ml, linearity to 1000 ng/ml, precision of 10% (CV%) in the low ng/ml region, approximate chromatography time of 25 minutes and the use of a new internal standard, WY-19083.

We consider coulombic interactions between particles confined to a region between two half spaces of a dielectric constant different to that of the region in between and with periodic boundary conditions with square unit cells imposed along the surfaces of the plane slab shaped region. We find two representations for the resulting lattice sums and discuss the construction of an algorithm which can optimize numerical performance (in terms of computer time) by using the two representations in different circumstances. Analysis of the resulting algorithm for the coulombic interactions shows that the computation time for the optimized algorithm for an N particle system should grow as N5/3.

Methods for obtaining a static dielectric constant ε from measurements of mean square dipole moment in a simulation are discussed. The simulations are seen as models of a macroscopic experiment to measure the dielectric constant. Such an experiment is usually carried out on a macroscopic sample of fixed shape. This sample is modelled by an array of copies of a microscopic simulation sample, the array having the appropriate shape. The different shapes correspond to different macroscopic experiments. The periodic boundary condition simulation sample hamiltonians appropriate to some different macroscopic geometries are described and appropriate fluctuation formulae for the dielectric constant obtained. The formulae are illustrated by simulations of fairly weakly dipolar molecules (which are rigid models of methyl chloride molecules) using samples of 27, 64, 125 and 216 molecules. All sample sizes give the same dielectric constant to within the error in the simulations, but the structure obtained for 27 molecules seems slightly distorted by small sample sizes. The measured wavevector dependent dielectric tensor ε(k) appears able to be extrapolated to k = 0 to agree with the values of ε obtained.

We use the Percus-Yevick approximation to study indirect correlation functions in the sticky hard-sphere model introduced by Baxter. The model has a critical point below which there is a liquid gas transition. We illustrate the changes in the structure of the correlation function as the density increases on the critical isotherm and on supercritical and subcritical isotherms. We also examine the local effects on this structure of introducing a large isolated sticky particle. For the gas part of the subcritical isotherm, such a particle can act as a condensation nucleus. We examine the dependence of the structure changes on the radius of the large particle.

Plasma levels of LH were measured in young sexually mature (2- to 5-month-old) and aged (13- to 20-month-old) female C57BL/6 mice, Syrian hamsters and Wistar rats using a radioimmunoassay (RIA) and a radioreceptor assay (RRA). There were no statistically significant differences when comparing data from the two assays when examining young oestrous and dioestrous mice. Aged oestrous and dioestrous mice exhibited significantly higher levels of LH as measured by RIA than by RRA. Levels of LH analysed by RIA were also higher in aged mice compared with those in younger mice. Comparing LH concentrations with the two types of assays in younger dioestrous and aged anoestrous hamsters produced similar results. In contrast, aged pseudopregnant rats exhibited significantly lower levels of plasma LH than younger dioestrous females and there were no differences in RIA and RRA values. There were also no differences when comparing data from the two assays in younger rats. The mean (± s.e.m.) RRA: RIA ratios of 0·96 ± 0·05 (oestrous) and 0·96 ± 0·04 (dioestrous) for younger mice and 0·92 ± 0·08 for younger hamsters were significantly higher than the ratios of 0·66 ± 0·72± 0·05 and 0·71 ± 0·05 respectively of their aged counterparts. The mean RRA: RIA ratios in the two age groups of rats were almost identical (0·79 ± 0·05 and 0·80 ± 0·10). These studies suggested that a portion of the higher LH levels detectable by RIA in some aged female rodents results from qualitative changes in the LH molecule.

The effects of acetazolamide, amiloride, furosemide, ouabain and theophylline on nerve-induced prostatic secretion were determined in pentobarbital-anesthetized dogs. In one set of experiments the glands were exposed to normal saline or drug-containing saline between periods of nerve-induced secretion by connecting a urethral cannula for 30-min periods to a buret filled with normal saline or drug-containing saline at a height of 100 cm above the gland and by allowing retrograde penetration of these solutions into the gland. Secretion in response to stimulation of the hypogastric nerves at 20 Hz was markedly inhibited by intraurethral exposure to 0.1 and 1 mM ouabain but not to 10 mM furosemide, 3 mM amiloride or 30 mM theophylline; responses to stimulation at 2 Hz were potentiated by 30 mM theophylline. In other experiments, secretion in response to stimulation at 20 Hz was inhibited by i.v. administration of 10 to 30 mg/kg of furosemide but not 2 to 8 mg/kg of amiloride or 18.5 to 25 mg/kg of acetazolamide. Because active Cl- transport is a major process in canine prostatic fluid formation and because secretion of this fluid was selectively modified by these drugs in the same manner as is Na+,K+-coupled active Cl- transport by a variety of other epithelia, these epithelia appear to share a common Cl- transporting system.

The establishment of a comprehensive retrospective clinicopathological database of patients who died with traumatic spinal injury is described. All necropsy patients examined from 1957 onwards, at the Royal Perth Hospital (RPH) with either a spinal cord or spinal column injury or both were included in the study. There are two broad categories of material. Firstly, those patients with a spinal cord injury (SCI) who survived the initial episode and were treated in the Sir George Bedbrook Department of Paraplegia, RPH. Secondly there are those who suffered either a vertebral column or SCI and died immediately, referred by the Coroner. In most cases, in both groups the spinal injury was not the direct cause of death. The catchment area includes the entire state of Western Australia. The database is essentially a neuropathological resource and is not intended to have any direct epidemiological implications. The information in the database is available for clinicopathological research such as:(a) To assist the clinician in planning the bedside management of patients with SCI.(b) To assess and quantify preserved anatomical structures for correlation with residual physiology in human SCI as a foundation for restorative neurology.(c) To define the spinal cord lesion in detail as a framework for the application of the many recent advances in basic neurobiology toward the reconstruction of the injured spinal cord.(d) To provide clinical data for use in conjunction with the tissue bank of spinal injuries established at RPH, in further research.

We consider the statistical mechanics of a fluctuating string (1D solid-on-solid model) ofN columns with a contact energy term displaying a critical wetting transition. For this model we derive a contour integral representation for the finite-size partition function. From this representation we derive a polynomial representation and obtain the Lee-Yang zeros forN ?, 100. Through the asymptotic evaluation of the contour integral we evaluate the zeros for higherN. This asymptotic evaluation displays a Stokes phenomenon providing a different viewpoint of the mechanism by which a phase transition can arise, supplementing the picture of Lee and Yang. We also reproduce and extend somewhat the results of Smith for the finite-size scaling limit of the partition function.

Studies of the mean spherical model with Coulomb interactions are continued, by considering a system on ad-dimensional lattice which is periodic ind-1 dimensions and has a free surface in the remaining dimension. It is shown explicitly that correlations along the free surface decay asy-dind dimensions and show that the surface properties of this model are those expected for a charged system in its plasma phase.

We derive a finite-size scaling representation for the partition function for an Onsager-Temperley string model with a wetting transition, and analyze the zeros of this partition function in the complex scaled coupling parameter of relevance. The system models the one-dimensional interface between two phases in a rectangular two-dimensional region (x, y) ?R2,-L =y?L,o=x=N. The two phases are at coexistence. The string or interface has a surface tension 2KkT per unit length and an extra Boltzmann weighta per unit length if it touches the surfaces aty=±L. There is a critical valueac=1/2K and fora>ac the string is confined to one of the surfaces, while fora tac the string moves roughly in the rectangular region. The finite-size scaling parameters are a=ac2N/L2 and ?=L(a-ac)/ac2. We find that for |?| large, the zeros of the scaled partition function lie close to the lines arg(?)=±p/4 with re(?)>0. We discuss the motion of all the zeros as a changes by both analytic and numerical arguments.

A mean spherical model of classical dipoles on a simple cubic lattice of sideM=2N+1 sites is considered. Exact results are obtained for finite systems using periodic boundary conditions with an external dielectric constant?' and using reaction field boundary conditions with a cutoff radiusRc?N and an external dielectric constant?'. The dielectric constant in the disordered phase is calculated using a variety of fluctuation formulas commonly implemented in Monte Carlo and molecular dynamics simulations of dipolar systems. The coupling in the system is measured by the parametery=4pµ2/9kT, whereµ2 is the fixed mean square value of the dipole moments on the lattice. The system undergoes a phase transition aty˜2.8, so that very high dielectric constants cannot be obtained in the disordered phase. The results show clearly the effects of system size, cutoff radius, external dielectric constant, and different measuring techniques on a dielectric constant estimate. It is concluded that with periodic boundary conditions, the rate of approach of the dielectric constant estimate to its thermodynamic limit is asN-2/3 and depends only weakly on?'. Methods of implementing reaction field boundary conditions to give rapid convergence to the thermodynamic limit are discussed.

We consider simple cubic lattice systems? ind dimensions with a continuous real charge variableq(n) at each lattice siten. These variables are subject t'o a mean spherical constraint forcing n??q2(n)>=???Q2, where ??? is the number of lattice sites in? andQ is an elementary charge. The energy of the charges comes from interactions with an electrostatic potential, which is the solution of a symmetric second-difference Poisson equation on the lattice. Two cases are considered, both of which allow the inclusion of the effects of a fixed, constant, external electric field. On the lattice?1=[1,N]?d, a Neumann condition is imposed at the surface of the lattice. The lattice?2=[1,N]? [-M,M]?(d-1) is periodic in each direction ranging over [-M, M] and has a Dirichlet condition imposed at the other two surfaces. On?2 a finite electric field may be applied, while on?2 a finite potential difference may be applied across the lattice. The models are exactly solvable. We study the distribution functions on each system and show that they satisfy appropriate forms of the first two Stillinger-Lovett moment conditions. The two charge distribution functions show screening behavior at high temperature and extreme short range at an intermediate temperatureT0(d), and oscillate as they decay to zero forT0(d). Because of the continuous nature of the charge variables, there is no Kosterlitz-Thouless transition in two dimensions. In three dimensions the change in the decay behavior of the distribution functions atT0(d) is precursor to a phase transition to a charge ordered state.

A model of a binary mixture, showing a wetting transition, is examined. No prewetting phenomena are found. The scaling functions are obtained for the film thickness and for the correlation lengths.

We derive adsorption isotherms for an adsorbate of hard-sphere particles with “sticky” interactions at any fluid density being adsorbed onto a plane, “sticky” surface. The theory is based on the Percus-Yevick theory for bulk fluids and explicitly includes the equilibrium between the adsorbed fluid and the bulk adsorbate. The theory predicts a surface condensation at low temperatures and low bulk densities in good agreement with surface condensations found in experimental studies of adsorption of gases onto graphite. An approximate law of corresponding states for these transitions is developed. At higher bulk densities and room temperatures, the adsorption isotherms can show a maximum, in accord with recent experimental work.

Some of the problems associated with Monte Carlo and molecular dynamics simulations of three dimensional ionic and dipolar systems are discussed, with emphasis on the use of periodic boundary conditions (PBC). It is shown that analogous problems may arise in two dimensional systems provided that the interactions are two dimensional electrostatic interactions, that is, interactions derived from the two dimensional Laplace equation. The PBC hamiltonian is evaluated by considering the appropriate two dimensional lattice sums, and a computable form for the effective pair interactions in PBC developed. The idea of an external dielectric constant is introduced and its effects included in the PBC hamiltonian. Formulae for evaluating the dielectric constant from a simulation with any external dielectric constant are given. Perturbation formulae showing the effects on the structure and mean square dipole moment of a dipolar system which are caused by a change in external dielectric constant are derived. A formula for the shift in mean square dipole moment of an ionic system is also developed. The problem of interpreting results from such simulations is discussed briefly.

The structure and dielectric properties of the hard sphere dipolar fluid, calculated using both perturbation theory and computer simulation, are reported. Both methods predict a short ranged hΔ(r), a much lower dielectric constant than previously obtained, and non-zero higher spherical harmonic coefficients of the angular correlation function.

Sphingosine, sphinganine, and other long-chain (sphingoid) bases are highly bioactive intermediates of sphingolipid metabolism that have diverse effects when added to cells, including the inhibition of protein kinase C (PKC) as evaluated by both enzymatic activity and [3H]phorbol dibutyrate ([3H]PDBu) binding. Nonetheless, changes in endogenous sphingoid bases have not been proven to affect PKC or other signal transduction pathways. We have discovered recently that changing J774A.1 cells to new medium results in up to 10-fold increases in sphingoid bases (Smith, E. R., and Merrill, A. H., Jr. (1995) J. Biol. Chem. 270, 18749-18758); therefore, this system was used to elevate sphingosine and sphinganine and determine if PKC was affected. Incubation of J774A.1 cells in new medium for 30 min increased the levels of these endogenous sphingoid bases to approximately 0.5 nmol/mg of protein and decreased [3H]PDBu binding by 40-60%. Addition of NH4Cl, which suppresses the change in sphingosine, restored [3H]PDBu binding. Elevation of endogenous sphinganine by a second method (addition of fumonisin B1, an inhibitor of ceramide synthase) also reduced [3H]PDBu binding; therefore, elevations in sphingosine and sphinganine can both affect PKC. The elevation in sphingoid bases was also associated with an increase in the amount of PKC-delta (the major PKC isozyme in J774A. 1 cells) in the cytosol, as determined by activity assays and immunoblot analyses. Changing the culture medium affected other PKC isozymes, increased cellular levels of diacylglycerol, dihydroceramide, and ceramide, and altered the expression of two genes (the expression of JE was increased, and the induction of MnSOD by TNF-alpha was potentiated). Thus, changing the culture medium has numerous effects on J774A.1 cells, including the modulation of PKC by endogenous sphingoid bases.