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Molecular dynamics simulations based on the Girifalco central two-body potential are performed in order to study bulk properties of solid C76 and C84. The fullerene cages are modelled as rigid sphere whose ‘effective’ diameter is first determined in such a way that NVT–NPT simulations of the model fullerite reproduce the experimental lattice constant at ambient pressure and at various temperatures. It turns out that the diameter so fixed depends only slightly on the temperature. A unique molecular size, yielding the fit of the lattice constant at a conveniently chosen temperature, is then adopted throughout the whole temperature ranges investigated; the lattice constants, and the internal potential energy of C76 and C84 thereby calculated at various T, turn out to be in qualitative agreement with the available experimental data. The equation of state at ambient temperature is then also calculated. Results for C76 compare favorably with experiment only at low pressures; by converse, results for C84 turn out to be qualitatively or semi-quantitatively accurate up to 9 GPa. Other possible applications of the model are discussed. [Copyright &y& Elsevier]

The free energy of the solid and fluid phases of the Girifalco C[sub 60] model are determined through extensive Monte Carlo simulations. In this model the molecules interact through a spherical pair potential, characterized by a narrow and attractive well, adjacent to a harshly repulsive core. We have used the Widom test particle method and a mapping from an Einstein crystal in order to estimate the absolute free energy in the fluid and solid phases, respectively; we have then determined the free energy along several isotherms, and the whole phase diagram, by means of standard thermodynamic integrations. The dependence of the simulation's results on the size of the sample is also monitored in a number of cases. We highlight how the interplay between the liquid-vapor and the liquid-solid coexistence conditions determines the existence of a narrow liquid pocket in the phase diagram, whose stability is assessed and confirmed in agreement with previous studies. In particular, the critical temperature follows closely an extended corresponding-state rule recently outlined by Noro and Frenkel [J. Chem. Phys. 113, 2941 (2000)]. We discuss the emerging "energetic" properties of the system, which drive the phase behavior in systems interacting through short-range forces [A. A. Louis, Philos. Trans. R. Soc. London, Ser. A 359, 939 (2001)], in order to explain the discrepancy between the predictions of several structural indicators and the results of full free energy calculations, to locate the fluid phase boundaries. More generally, we aim to provide extended reference data for calculations of the free energy of the C60 fullerite in the low temperature regime, as for the determination of the phase diagram of higher order C[sub n]>60 fullerenes and other fullerene-related materials, whose description is based on the same model adopted in this work. [ABSTRACT FROM AUTHOR]

We show by extensive molecular dynamics simulations that accurate predictions of liquid-vapor coexistence in molten alkali halides can be achieved in terms of a rigid ion potential description in which temperature-dependent ionic diameters are employed. The new ionic sizes result from the fitting of the experimental isothermal compressibilities, a condition whose physical implications and consequences are illustrated. The same diameters also allow us to formulate confident predictions for the compressibilities of salts in cases where the experimental data are lacking. The extension of the present approach to molten alkali-halide mixtures and to other classes of molten salts is discussed.

The emergence of supramolecular aggregates from simple microscopic interaction rules is a fascinating feature of complex fluids which, besides its fundamental interest, has potential applications in many areas, from biological self-assembly to smart material design. We here investigate by Monte Carlo simulation the equilibrium structure of a two-dimensional mixture of asymmetric dimers and spheres (disks). Dimers and disks are hard particles, with an additional short-range attraction between a disk and the smaller monomer of a dimer. The model parameters and thermodynamic conditions probed are typical of colloidal fluid mixtures. In spite of the minimalistic character of the interaction, we observe-upon varying the relative concentration and size of the two colloidal species-a rich inventory of mesoscale structures at low temperature, such as clusters, lamellæ (i.e., polymer-like chains), and gel-like networks. For colloidal species of similar size and near equimolar concentrations, a dilute fluid of clusters gives way to floating lamellæ upon cooling; at higher densities, the lamellæ percolate through the simulation box, giving rise to an extended network. A crystal-vapour phase-separation may occur for a mixture of dimers and much larger disks. Finally, when the fluid is brought in contact with a planar wall, further structures are obtained at the interface, from layers to branched patterns, depending on the nature of wall-particle interactions.

We report extensive calculations, based on the modified hypernetted chain (MHNC) theory, on the hierarchical reference theory (HRT), and on Monte Carlo simulations, of thermodynamical, structural and phase coexistence properties of symmetric binary hard-core Yukawa mixtures (HCYM) with attractive interactions at equal species concentration. The obtained results are throughout compared with those available in the literature for the same systems. It turns out that the MHNC predictions for thermodynamic and structural quantities are quite accurate in comparison with the MC data. The HRT is equally accurate for thermodynamics, and slightly less accurate for structure. Liquid-vapor (LV) and liquid-liquid (LL) consolute coexistence conditions as emerging from simulations, are also highly satisfactorily reproduced by both the MHNC and HRT for relatively long ranged potentials. When the potential range reduces, the MHNC faces problems in determining the LV binodal line; however, the LL consolute line and the critical end point (CEP) temperature and density turn out to be still satisfactorily predicted within this theory. The HRT also predicts with good accuracy the CEP position. The possibility of employing liquid state theories HCYM for the purpose of reliably determining phase equilibria in multicomponent colloidal fluids of current technological interest, is discussed.

We investigate the structure of a dilute mixture of amphiphilic dimers and spherical particles, a model relevant to the problem of encapsulating globular "guest" molecules in a dispersion. Dimers and spheres are taken to be hard particles, with an additional attraction between spheres and the smaller monomers in a dimer. Using the Monte Carlo simulation, we document the low-temperature formation of aggregates of guests (clusters) held together by dimers, whose typical size and shape depend on the guest concentration χ. For low χ (less than 10%), most guests are isolated and coated with a layer of dimers. As χ progressively increases, clusters grow in size becoming more and more elongated and polydisperse; after reaching a shallow maximum for χ≈50%, the size of clusters again reduces upon increasing χ further. In one case only (χ=50% and moderately low temperature) the mixture relaxed to a fluid of lamellae, suggesting that in this case clusters are metastable with respect to crystal-vapor separation. On heating, clusters shrink until eventually the system becomes homogeneous on all scales. On the other hand, as the mixture is made denser and denser at low temperature, clusters get increasingly larger until a percolating network is formed.

Inspired by significant improvements obtained for the performances of the polymer reference interaction site model (PRISM) theory of the fluid phase when coupled with 'molecular closures' (Schweizer and Yethiraj 1993 J. Chem. Phys. 98 9053), we exploit a matrix generalization of this concept, suitable for the more general RISM framework. We report a preliminary test of the formalism, as applied to prototype square-well homonuclear diatomics. As for the structure, comparison with Monte Carlo shows that molecular closures are slightly more predictive than their 'atomic' counterparts, and thermodynamic properties are equally accurate. We also devise an application of molecular closures to models interacting via continuous, soft-core potentials, by using well established prescriptions in liquid state perturbation theories. In the case of Lennard-Jones dimers, our scheme definitely improves over the atomic one, providing semi-quantitative structural results, and quite good estimates of internal energy, pressure and phase coexistence. Our finding paves the way to a systematic employment of molecular closures within the RISM framework to be applied to more complex systems, such as molecules constituted by several non-equivalent interaction sites.

We perform structural and thermodynamic calculations in the framework of the modified hypernetted chain (MHNC) integral equation closure to the Ornstein-Zernike equation for binary mixtures of size-different particles interacting with hard-core Yukawa pair potentials. We use the Percus-Yevick (PY) bridge functions of a binary mixture of hard-sphere (HSM) particles. The hard-sphere diameters of the PY bridge functions of the HSM system are adjusted so to achieve thermodynamic consistency between the virial and compressibility equations of state. We show the benefit of thermodynamic consistency by comparing the MHNC results with the available computer simulation data reported in the literature, and we demonstrate that the self-consistent thermodynamic theory provides a better reproduction of the simulation data over other microscopic theories.

We study by Monte Carlo simulation the coating process of colloidal dimers onto spherical nanoparticles. To this end we investigate a simplified mixture of hard spheres (the guest particles) and hard dimers formed by two tangent spheres of different sizes (the encapsulating agents) in an implicit-solvent representation; in our scheme, the range of effective interactions between the smaller particle in a dimer and a guest sphere depends on their relative size. By tuning the size and concentration of guests, under overall dilute conditions a rich phase behavior emerges: for small sizes and/or low concentrations, the preferred arrangement is compact aggregates (capsules) of variable sizes, where one or few guest particles are coated with dimers; for larger sizes and moderate guest concentrations, other scenarios are realized, including equilibrium separation between a guest-rich and a guest-poor phase. Our results serve as a framework for a more systematic investigation of self-assembled structures of functionalized dimers capable of encapsulating target particles, like for instance bioactive substances in a colloidal dispersion.

In this study, Boltzmann inversion is applied in conjunction with molecular dynamics simulations to derive inter-molecular potential for protein lysozyme in aqueous solution directly from experimental static structure factor. The potential has a soft repulsion at short distances and an attraction well at intermediate distances that give rise to the liquid-liquid phase separation. Moreover, Gibbs ensemble Monte Carlo simulations demonstrate that a non-spherical description of lysozyme is better suited to correctly reproduce the experimentally observed properties of such a phase separation. Our findings shed new light on the common problem in molecular and cell biology: "How to model proteins in their natural aqueous environments?"

Context: Available markers are not reliable parameters to early detect kidney injury in transplanted patients., Objective: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome., Patients and Methods: NGAL was evaluated in 124 transplanted patients., Results: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04-1.25; p < 0.001) and 15% (HR: 1.15; 95% CI: 1.09-1.26; p < 0.001) increased risk of DGF and allograft nephropathy progression, respectively., Conclusion: NGAL reflects the entity of renal impairment in transplanted patients, representing a biomarker and an independent risk factor for DGF and chronic allograft nephropathy progression.

Within the coexistence region between liquid and vapor the equilibrium pressure of a simulated fluid exhibits characteristic jumps and plateaus when plotted as a function of density at constant temperature. These features exclusively pertain to a finite-size sample in a periodic box, as they are washed out in the bulk limit. Below the critical density, at each pressure jump the shape of the liquid drop undergoes a morphological transition, changing from spherical to cylindrical to slablike as the density is increased. We formulate a simple theory of these shape transitions, which is adapted from a calculation originally developed by Binder and coworkers [L. G. MacDowell, P. Virnau, M. Muller, and K. Binder, J. Chem. Phys. 120, 5293 (2004)]. Our focus is on the pressure equation of state (rather than on the chemical potential, as in the original work) and includes an extension to elongated boxes. Predictions based on this theory well agree with extensive Monte Carlo data for the cut-and-shifted Lennard-Jones fluid. We further discuss the thermodynamic stability of liquid drops with shapes other than the three mentioned above, like those found deep inside the liquid-vapor region in simulations starting from scratch. Our theory classifies these more elaborate shapes as metastable.

We investigate thermodynamic properties of anisotropic colloidal dumbbells in the frameworks provided by the Reference Interaction Site Model (RISM) theory and an Optimized Perturbation Theory (OPT), this latter based on a fourth-order high-temperature perturbative expansion of the free energy, recently generalized to molecular fluids. Our model is constituted by two identical tangent hard spheres surrounded by square-well attractions with same widths and progressively different depths. Gas-liquid coexistence curves are obtained by predicting pressures, free energies, and chemical potentials. In comparison with previous simulation results, RISM and OPT agree in reproducing the progressive reduction of the gas-liquid phase separation as the anisotropy of the interaction potential becomes more pronounced; in particular, the RISM theory provides reasonable predictions for all coexistence curves, bar the strong anisotropy regime, whereas OPT performs generally less well. Both theories predict a linear dependence of the critical temperature on the interaction strength, reproducing in this way the mean-field behavior observed in simulations; the critical density—that drastically drops as the anisotropy increases—turns to be less accurate. Our results appear as a robust benchmark for further theoretical studies, in support to the simulation approach, of self-assembly in model colloidal systems.

Specialized Monte Carlo methods are nowadays routinely employed, in combination with thermodynamic integration (TI), to locate phase boundaries of classical many-particle systems. This is especially useful for the fluid-solid transition, where a critical point does not exist and both phases may notoriously go deeply metastable. Using the Lennard-Jones model for demonstration, we hereby investigate on the alternate possibility of tracing reasonably accurate transition lines directly by integrating the pressure equation of state computed in a canonical-ensemble simulation with local moves. The recourse to this method would become a necessity when the stable crystal structure is not known. We show that, rather counterintuitively, metastability problems can be alleviated by reducing (rather than increasing) the size of the system. In particular, the location of liquid-vapor coexistence can exactly be predicted by just TI. On the contrary, TI badly fails in the solid-liquid region, where a better assessment (to within 10% accuracy) of the coexistence pressure can be made by following the expansion, until melting, of the defective solid which has previously emerged from the decay of the metastable liquid.

We numerically investigate colloidal dimers with asymmetric interaction strengths to study how the interplay between molecular geometry, excluded volume effects and attractive forces determines the overall phase behavior of such systems. Specifically, our model is constituted by two rigidly-connected tangent hard spheres interacting with other particles in the first instance via identical square-well attractions. Then, one of the square-well interactions is progressively weakened, until only the corresponding bare hard-core repulsion survives, giving rise to a "Janus dumbbell" model. We investigate structure, thermodynamics and phase behavior of the model by means of successive umbrella sampling and Monte Carlo simulations. In most of the cases, the system behaves as a standard simple fluid, characterized by a gas-liquid phase separation, for sufficiently low temperatures. In these conditions we observe a remarkable linear scaling of the critical temperature as a function of the interaction strength. But, as the interaction potential approaches the Janus dumbbell limit, we observe the spontaneous formation of self-assembled lamellar structures, preempting the gas-liquid phase separation. Comparison with previous studies allows us to pinpoint the role of the interaction range in controlling the onset of ordered structures and the competition between the formation of these structures and gas-liquid condensation.

Vasopressin (AVP) plays a detrimental role in autosomal dominant polycystic kidney disease (ADPKD). Copeptin represents a measurable substitute for circulating AVP whereas apelin counteracts AVP signaling. The aim of this study was to investigate the predictive value of apelin and copeptin for the progression of ADPKD disease. 52 ADPKD patients were enrolled and followed until the end of the observation period or the primary study endpoint was reached, defined by the combined outcome of decrease of glomerular filtration rate associated with a total renal volume increase. Receiver operating characteristics (ROC) analysis was employed for identifying the progression of renal disease and Kaplan-Meier curves assessed the renal survival. Adjusted risk estimates for progression endpoint and incident renal replacement therapy (RRT) were calculated using Cox proportional hazard regression analysis. ADPKD patients were characterized by lower apelin levels and higher copeptin levels when compared with healthy subjects. These biomarkers were strictly correlated with osmolality and markers of renal function. At ROC analysis, apelin and copeptin showed a very good diagnostic profile in identifying ADPKD progression. After the follow up of 24 months, 33 patients reached the endpoint. Cox proportional hazard regression analysis showed that apelin predicted renal disease progression and incident RRT independently of other potential confounders. Apelin is associated with kidney function decline in ADPKD, suggesting that it may be a new marker to predict kidney outcome., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We report the determination of an effective protein-protein central potential for a lysozyme solution, obtained from the direct inversion of the total structure factor of the system, as extracted from small angle neutron scattering. The inversion scheme rests on a hypernetted-chain relationship between the effective potential and the structural functions, and is preliminarily tested for the case of a Lennard-Jones interaction. The characteristics of our potential are discussed in comparison with current models of effective interactions in complex fluids. The phase behavior predictions are also investigated.

We report protein-protein structure factors of aqueous lysozyme solutions at different pH and ionic strengths, as determined by small-angle neutron scattering experiments. The observed upturn of the structure factor at small wavevectors, as the pH increases, marks a crossover between two different regimes, one dominated by repulsive forces, and another one where attractive interactions become prominent, with the ensuing development of enhanced density fluctuations. In order to rationalize such experimental outcome from a microscopic viewpoint, we have carried out extensive simulations of different coarse-grained models. We have first studied a model in which macromolecules are described as soft spheres interacting through an attractive r(-6) potential, plus embedded pH-dependent discrete charges; we show that the uprise undergone by the structure factor is qualitatively predicted. We have then studied a Derjaguin-Landau-Verwey-Overbeek (DLVO) model, in which only central interactions are advocated; we demonstrate that this model leads to a protein-rich/protein-poor coexistence curve that agrees quite well with the experimental counterpart; experimental correlations are instead reproduced only at low pH and ionic strengths. We have finally investigated a third, "mixed" model in which the central attractive term of the DLVO potential is imported within the distributed-charge approach; it turns out that the different balance of interactions, with a much shorter-range attractive contribution, leads in this latter case to an improved agreement with the experimental crossover. We discuss the relationship between experimental correlations, phase coexistence, and features of effective interactions, as well as possible paths toward a quantitative prediction of structural properties of real lysozyme solutions., (© 2012 American Institute of Physics)

Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 [6986A>G] as well as ABCB1 at exons 21 [2677G>T/A] and 26 [3435C>T] in both liver transplant donors and recipients and in kidney transplant recipients. Of the 152 subjects studied, 84.9% showed a CYP3A5*3/*3 genotype. The total frequency of the allelic variant *3 was 93%. For the G2677T/A and C3435T polymorphisms the total frequencies of the allelic variants T/A and T were 44.7 and 46.7%, respectively. At 1, 3 and 6 months after transplantation the dose-adjusted C0 levels were significantly lower in patients with one copy of the *1 allele compared to those homozygous for the *3 allele. In the case of liver transplant patients the tacrolimus dose requirements were dominantly influenced by the polymorphisms of the CYP3A5 gene in the donors. With regard to the ABCB1 SNPs, in general they did not show any appreciable influence on tacrolimus dosing requirements; however, kidney transplant recipients carrying the 2677T/A allele required significantly higher daily tacrolimus doses than subjects homozygous for the wild-type allele. Identification of CYP3A5 single nucleotide polymorphisms prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus in the patients.

We study the thermodynamic and structural properties of a five-site tetrahedral molecular model by means of different Monte Carlo simulation techniques, and the reference interaction site model (RISM) theory of molecular fluids. Simulations and theory signal the onset, at sufficiently low temperatures, of two different tetrahedral molecular arrangements, with a more open topology progressively giving place to a fully bonded one, as the temperature decreases. The RISM theory reproduces the splitting of the static structure factor at low temperatures, a feature intimately related to the onset of the tetrahedral ordering. Less accurate predictions are obtained for the liquid-vapor coexistence and the short-range correlations., (© 2011 American Institute of Physics.)

We report molecular dynamics and reference interaction site model (RISM) theory of methanol and carbon tetrachloride mixtures. Our study encompasses the whole concentration range, by including the pure component limits. We majorly focus on an analysis of partial, total, and concentration-concentration structure factors, and examine in detail the k-->0 limits of these functions. Simulation results confirm the tendency of methanol to self-associate with the formation of ring structures in the high dilution regime of this species, in agreement with experimental studies and with previous simulations by other authors. This behavior emerges as strongly related to the high nonideality of the mixture, a quantitative estimate of which is provided in terms of concentration fluctuation correlations, through the structure factors examined. The interaggregate correlation distance is also thereby estimated. Finally, the compressibility of the mixture is found in good agreement with experimental data. The RISM predictions are throughout assessed against simulation; the theory describes better the apolar solvent than the alcohol properties. Self-association of methanol is qualitatively reproduced, though this trend is much less marked in comparison with simulation results.

We revisit the thermodynamic and structural properties of fluids of homonuclear hard dumbbells in the framework provided by the reference interaction site model (RISM) theory of molecular fluids. Besides the previously investigated Percus-Yevick (PY) approximation, we test the accuracy of other closures to the RISM equations, imported from the theory of simple fluids; specifically, we study the hypernetted chain (HNC), the modified HNC (MHNC) and, less extensively, the Verlet approximations. We implement our approach for models characterized by several different elongations, up to the case of tangent diatomics, and investigate the whole fluid density range. The theoretical predictions are assessed against Monte Carlo simulations, either available from literature or newly generated by us. The HNC and PY equations of state, calculated via different routes, share on the whole the same level of accuracy. The MHNC is applied by enforcing an internal thermodynamic consistency constraint, leading to good predictions for the equation of state as the elongation of the dumbbell increases. As for the radial distribution function, the MHNC appears superior to other theories, especially for tangent diatomics in the high density limit; the PY approximation is better than the HNC and Verlet closures in the high density or elongation regime. Our structural analysis is supplemented by an accurate inversion procedure to reconstruct from Monte Carlo data and RISM the "exact" direct correlation function. In agreement with such calculations and consistent with the forecast of rigorous diagrammatic analysis, all theories predict the occurrence in the direct correlation function of a first cusp inside the dumbbell core and (with the obvious exception of the PY) of a second cusp outside; the cusps' heights are also qualitatively well reproduced by the theories, except at high densities.

Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR) inhibitors for calcineurin inhibitors.

We use theory and computer simulation to study the structure and phase behavior of colloid-polymer mixtures in the presence of quenched disorder. The Asakura-Oosawa model (AO) (Asakura and Oosawa 1954 J. Chem. Phys. 22 1255) is used to describe the colloid-colloid, colloid-polymer, and polymer-polymer pair interactions. We then investigate the behavior of this model in the presence of frozen-in (quenched) obstacles. The obstacles will be placed according to two different scenarios, both of which are experimentally feasible. In the first scenario, polymers are distributed at positions drawn from an ideal gas configuration. In the second scenario, colloidal particles are distributed at positions drawn from an equilibrium hard sphere configuration. We investigate how the unmixing transition of the AO model is affected by the type of quenched disorder. The theoretical formalism is based on the replica method of Given and Stell (1994 Physica A 209 495). Our foremost aim is to test the accuracy of three common closures to the replica Ornstein-Zernike equations, namely the hypernetted chain, the Percus-Yevick, and the Martinov-Sarkisov equations. The accuracy is determined by comparison with grand canonical Monte Carlo simulations. We find that, for quenched polymer disorder, all three closures perform remarkably well. However, when quenched colloid disorder is considered, i.e. the second mentioned scenario, the predictions of all three closures worsen dramatically.

Thermodynamic and structural properties of various models of liquid methanol are investigated in the framework provided by the reference interaction site model (RISM) theory of molecular fluids. The theoretical predictions are systematically compared with molecular dynamics simulations both at ambient conditions and along a few supercritical isotherms. RISM results for the liquid-vapor phase separation are also obtained and assessed against available Gibbs ensemble Monte Carlo data. At ambient conditions, the theoretical correlations weakly depend on the specific details of the molecular models and reproduce the simulation results with different degrees of accuracy, depending on the pair of interaction sites considered. The position and the strength of the hydrogen bond are quite satisfactorily predicted. RISM results for the internal energy are almost quantitative whereas the pressure is generally overestimated. As for the liquid-vapor phase coexistence, RISM predictions for the vapor branch and for the critical temperature are quite accurate; on the other side, the liquid branch densities, and consequently the critical density, are underestimated. We discuss our results in terms of intrinsic limitations, and suitable improvements, of the RISM approach in describing the physical properties of polar fluids, and in the perspective of a more general investigation of mixtures of methanol with nonpolar fluids of specific interest in the physics of associating fluids.

Objective: To evaluate any correlations between erythropoietin (EPO) and vascular endothelial growth factor (VEGF) levels in the serum and the menstrual fluid of healthy women during the different phases of the menstrual cycle., Study Design: Blood samples from 25 healthy female volunteers were obtained for serum VEGF and EPO detection on the 1st, 7th, 14th, 21st and 25th days of the menstrual cycle. Menstrual fluid samples for VEGF and EPO detection were obtained on the 1st and 4th days of menstruation., Results: Circulating VEGF levels were found to increase in a stage-dependent cyclic manner. The mean VEGF concentration in menstrual blood on the 1st day of the cycle was significantly higher than the mean plasma value and was reduced to a significant extent on the 4th day of the cycle. We found no significant changes in serum EPO levels. Mean EPO concentration detected in menstrual blood was comparable to those in serum blood either on the 1st or 4th day of the menstrual cycle., Conclusion: During menstruation, a local production of VEGF occurs independent of systemic production, thus sustaining angiogenic activity in autonomous, independent ways. Our findings demonstrate the presence of an "open compartment" that reflects the systemic pattern of EPO at the uterine level that allows us to speculate on different effects beyond the angiogenic action of EPO.

HMG-CoA reductase inhibitors (statins) are among the most widely used hypolypemizing drugs with a pleiotropic activity. Numerous clinical trials have demonstrated that statins can have a significant effect in the prevention of cardiovascular diseases in the general population. In patients with renal failure, this drug preserves the hypolypemizing efficacy found in the general population without increasing their unwanted side-effects. The re-analysis of data from epidemiological studies conducted on the general population has confirmed that statins provide cardiovascular protection also in subjects with renal failure. These data have been partly confirmed by the findings made by 4D (Die Deutsche Diabetes Dialyse Studie) and Alert studies, conducted on diabetic patients on dialysis and patients with renal transplants, respectively. The results of other studies, such as AURORA, SHARP, REnal and Vascular End stage Disease, and ESPLANADE, clearly indicate that statins prevent cardiovascular disease in patients with renal insufficiency, just as they do in the general population.

Background: In end-stage renal disease (ESRD) patients on hemodialysis (HD) there may be a link between oxidative stress, genomic damage and the tendency of peripheral lymphocytes to die by apoptosis. Our aim was to verify this hypothesis, and to ascertain whether the link, if present, could explain lymphopenia in uremic patients., Methods: The series investigated comprised 55 participants: 30 HD patients on regular maintenance acetate-free bio-filtration (AFB) and 25 age-matched healthy volunteers. One blood sample was drawn from the cubital vein of each participant. In HD patients, samples were drawn 3 times: predialytic, postdialytic and interdialytic (24 hours after the end of the session). Thiobarbituric acid reactants (TBARs), sister chromatid exchange (SCE) rate, high frequency cells (HFCs), total circulating lymphocytes and the percentage of circulating apoptotic lymphocytes were assayed in all samples. A statistical analysis of the findings was made using multiple and linear regression., Results: In AFB patients, TBAR levels appeared higher than in controls, even at baseline (2.15 +/- 0.5 micromol/L vs. 1.20 +/- 0.4 micromol/L; p < 0.05). The highest peak occurred at the end of the session (3.2 +/- 0.4 micromol/L; p < 0.05 vs. basal), and a prompt return to basal values was observed 24 hours later (2.2 +/- 0.6 micromol/L, p < 0.5 vs. basal). In AFB patients, the per-centages of HFCs (8.63% vs. 3%; p < 0.05), SCE (6 +/- 0.6 vs. 4.65 +/- 2.18; p < 0.04) and apoptotic lymphocytes (3-fold) were greater than in controls, even at baseline, whereas the values for total lymphocytes were lower (1,140 +/- 652 vs. 1,590 +/- 822). After an AFB session the differences between patients and control values appeared greater (HFCs, 16.81%, p < 0.04 vs. basal; SCE, 7.02 +/- 1.2, p < 0.03; apoptotic lymphocytes 3.5-fold greater than control values). Twenty-four hours later, a further increase was observed in the expression of genomic damage (HFCs, 50%, p < 0.05 vs. basal; SCE, 9.82 +/- 2.1, p < 0.03) and the percentage of apoptotic lymphocytes (4.7-fold greater than control values), while the lowest peak occurred for total circulating lymphocyte count (997 +/- 854, p < 0.04). At linear regression, a strong positive correlation was found between HFCs and TBARs at the beginning and at the end of the AFB session(r = 0.7, p < 0.03). With multiple regression analysis, a strong positive correlation was found between TBAR levels at the end of AFB session, HFC rate and apoptotic lymphocytes at 24 hours, with the last as the dependent variable (multiple r = 0.8, TBARs, beta = 0.51, p < 0.04; HFCs, beta = 0.43, p < 0.03)., Discussion and Conclusions: An AFB session has an immediate impact, causing an increase in TBAR levels, genomic da-mage and lymphocytic apoptosis. Twenty-four hours after the session there was a further expression of genomic damage, and an increase in apoptosis, while the peak for lymphocytes dropped sharply. Our findings indicate that lymphopenia affecting end-stage renal disease (ESRD) patients may be strictly related to genomic damage exerted, at least in part, by TBARs, and to a dysregulation in programmed cell death.

We studied the thermodynamic stability of fluid-fluid phase separation in binary nonadditive mixtures of hard-spheres for moderate size ratios. We are interested in elucidating the role played by small amounts of nonadditivity in determining the stability of fluid-fluid phase separation with respect to the fluid-solid phase transition. The demixing curves are built in the framework of the modified-hypernetted chain and of the Rogers-Young integral equation theories through the calculation of the Gibbs free energy. We also evaluated fluid-fluid phase equilibria within a first-order thermodynamic perturbation theory applied to an effective one-component potential obtained by integrating out the degrees of freedom of the small spheres. A qualitative agreement emerges between the two different approaches. We also addressed the determination of the freezing line by applying the first-order thermodynamic perturbation theory to the effective interaction between large spheres. Our results suggest that for intermediate size ratios a modest amount of nonadditivity, smaller than earlier thought, can be sufficient to drive the fluid-fluid critical point into the thermodinamically stable region of the phase diagram. These findings could be significant for rare-gas mixtures in extreme pressure and temperature conditions, where nonadditivity is expected to be rather small.

In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage. Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration. Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82+/-2.1 vs. 4.65+/-2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage. Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients. In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity. Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque.

Extensive molecular dynamics simulations show that a short-range central potential, suited to model C60, undergoes a high temperature transition to a glassy phase characterized by the positional disorder of the constituent particles. Crystallization, melting, and sublimation, which also take place during the simulation runs, are illustrated in detail. It turns out that vitrification and the mentioned phase transitions occur when the packing fraction of the system-defined in terms of an effective hard-core diameter-equals that of hard spheres at their own glass and melting transition, respectively. A close analogy also emerges between our findings and recent mode coupling theory calculations of structural arrest lines in a similar model of protein solutions. We argue that the conclusions of the present study might hold for a wide class of potentials currently employed to mimic interactions in complex fluids (some of which are of biological interest), suggesting how to achieve at least qualitative predictions of vitrification and crystallization in those systems.

Background: The risk of developing cardiovascular diseases is higher in patients on haemodialysis than in the general population. These patients may develop arrhythmias that depend on the extra- and intracellular concentrations of potassium. ECG findings, particularly the QT interval and its dispersion (QT(d)) and the QT(c) (QT interval corrected for heart rate according to Bazett's formula) and its dispersion (QT(cd)), may be direct indicators of the risk of developing arrhythmia., Methods: Our cohort comprised 28 patients who were dialysed for 3.5-4 h three times per week, first with haemodiafiltration with a constant potassium concentration (HDF) in the dialysis bath then with haemodiafiltration with variable concentrations of potassium (HDF(k)). ECGs were done at different time intervals: at the start of dialysis (T(0)), at 15 (T(15)), 45 (T(45)), 90 (T(90)) and 120 min (T(120)) after the beginning of the session, and at the end of treatment (T(end)). ECG-derived data (QT, QT(d), QT(c) and QT(cd)) were measured. At the same time points, plasma electrolytes, intra-erythrocytic potassium and the electrical membrane potential at rest (REMP) of the erythrocytic membrane were measured., Results: Plasma potassium concentration diminished more gradually in HDF(k) than in HDF, the difference being statistically significant at T(15) and T(45) (P<0.05), and T(90) (P<0.01). The intra-erythrocytic potassium concentration remained constant throughout the observation period. In both HDF and HDF(k), REMP was lower at all points after T(0) (P<0.05), but the reduction was greater and more significant in HDF than in HDF(k) at T(15) and T(120) (P<0.05). ECG revealed a statistically significant diminution in HDF(k) vs HDF in the measures of dispersion of QT and QT(c) at T(15), T(90), T(120) and T(end) (P<0.01) and of QT(cd) at T(45) (P<0.05). The mean of QT(d), adjusted for plasma potassium, increased over time in HDF with large alternate mean increase and decrease peaks and error intervals. In HDF(k), instead, there was a progressive and constant diminution with minor error intervals. QT(cd) adjusted for plasma potassium had the same trend. A marked difference was found between the final values in standard HDF and those in HDF(k)., Conclusions: HDF and HDF(k) have significantly different effects on QT(c). ECG data demonstrate that the risk of arrhythmia could be lower, with a variable removal of potassium during haemodialysis. With HDF but not HDF(k), hyperpolarization of the cell membrane is detected, and this could have a destabilizing effect on different types of cardiac cell, giving rise to retrograde circuits.

Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia-induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neurotransmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issue, because of its possible action as a growth and an angiogenic factor. In our speculative hypothesis Epo could be involved in a "two steps process" that, after a neovascularization phase, leads to its down regulation. Moreover, Epo-activated signaling pathways could be modulated as possible targets to interfere in neoplastic cells cycle. In conclusion, treatment with rHuEpo could change therapeutical perspectives in different pathological conditions, such as central nervous system (CNS) diseases, but further studies are needed to clarify its physiopathological activities in different clinical fields.

Background and Aim: Our aim was to evaluate QTc interval and QTc dispersion in 27 end-stage renal disease (ESRD) patients undergoing Acetate Free Biofiltration (AFB) in order to ascertain any correlations between the electrrocardiographic (ECG) parameters, serum Na+, K+, Ca++, Mg++ and intraerythrocytic Mg++ (Mg++e) concentrations. All measures were made at t0 (session beginning), t1 (first hour), t2 (second hour), t3 (third hour), and t4 (session end)., Results: Blood pressure, heart rate, bodyweight and total ultrafiltration in the three dialysis sessions were constant. A significant progressive increase occurred in serum Ca++ during the sessions, while there was a significant diminution in serum K+. The pattern for Mg++ concentrations in serum and erythrocytes differed: in serum it decreased, whereas Mg++e increased. At t4, the QTc interval was reduced to a significant extent with respect to the baseline value. QTc dispersion significantly increased at t1 without there being significant variations at other times with respect to t0. At t2, t3 and t4, values promptly returned to baseline levels. QTc had a negative correlation with serum Ca++ levels at t4. In contrast, an inverse correlation was found between QTc dispersion and serum K+ at t1. No other correlations could be found between any other electrolytes, QTc interval or QTc dispersion., Conclusion: In conclusion, the decrease observed in the QTc interval at the end of an AFB session was inversely related to serum Ca++ concentrations. Moreover, an increase in QTc dispersion occurred during the first hour of the session, and was negatively correlated with serum K+.

We report on an extensive molecular dynamics investigation of two models of C60. The first model is based on an effective pair, central potential obtained by integrating the interaction between two carbon atoms over the fullerene cages [L.A. Girifalco, J. Phys. Chem. 96, 858 (1992)]. The second model explicitly takes into account the discrete, "atomistic" structure of the C60 molecules; we study two different parametrizations of the carbon-carbon interaction, one identical to that employed in the Girifalco approach, the other borrowed from previous studies on graphite [A. Cheng and M.L. Klein, J. Phys. Chem. 95, 6750 (1991)]. We consider a temperature range spanning from 300 to 1900 K, and pressures up to 200 kbar. Results for the lattice spacing and several thermodynamic quantities, as well as for the radial distribution functions, are reported and compared among each other and with experimental data. The central pair model yields only semiquantitative predictions at typical ambient densities, whereas pressures are generally overestimated. Atomistic simulations reproduce to an overall quantitative level of accuracy the experimental C60 properties. A comparison is also made of the central versus the atomistic potential predictions, when using the same potential parameters in the carbon-carbon interaction. We discuss applications of the adopted modelizations to fullerene systems of current interest, as well as different strategies to optimize the values of the potential parameters.

The Short Form 36 Health Survey (SF-36) is a self-administered scoring system that has been widely used and validated as a quality of life (QOL) assessment tool. In our study, a cluster analysis of SF-36 scores was performed in 50 healthy volunteers (controls) and 50 neurobiologically asymptomatic patients on maintenance hemodialysis (MHD). Firstly, we assayed the tendency to form clusters from each of the investigated dimensions. Statistic analysis was performed using the Student's t-test for independent measurements and multiple regression analysis. Secondly, we attempted to evaluate if the MHD to apply to both groups a general psychobiological personality model developed by Cloninger in 1987. Cloninger describes three independent personality dimensions: novelty seeking (NS), harm avoidance (HA)and reward dependence (RD). Each personality dimension would be the expression of hereditary variations integrating the three main brain systems, respectively: dopaminergic, serotoninergic and noradrenergic. Finally, we then aimed to investigate possible interferences among the seric concentrations of the neuromodulators and SF-36 scores, in the attempt to identify, using a simple approach, the complex personality structure of MHD patients. QOL self-assessment and seric neuromodulators were measured in both groups, choosing an interdialytic day for MHD patients. We found that MHD patients perceived a significant worsening in their QOL in all investigated dimensions with respect to the controls. In addition, they showed significantly lower dopamine and serotonine concentrations and significantly higher noradrenaline concentrations. Therefore, our study, confirmed data reported previously in the literature, that cluster analysis of SF-36 scores provides different results in the MHD population in comparison to normal subjects. In fact, comparing the hierarchical trees of both groups, it appeared evident that in MHD patients, cluster dimensions were greater than in the controls. In cluster compositions showed differences between the two groups. In fact, in MHD patients there were only a few of the clusters that were observed in the controls (mental health and social functioning, vitality and general health), while role-physical and role-emotional dimensions aligned outside the hierarchical tree, with a considerable linkage distance. In our opinion, it is fascinating that the three Cloninger neuromodulators could suggest that HD patient personalities are potentially cyclothymiac, altering the disposition of the two role functions inside the hierarchical tree.