Structure and dynamics of nanoconfined water and aqueous solutions.

This review is devoted to discussing recent progress on the structure, thermodynamic, reactivity, and dynamics of water and aqueous systems confined within different types of nanopores, synthetic and biological. Currently, this is a branch of water science that has attracted enormous attention of researchers from different fields interested to extend the understanding of the anomalous properties of bulk water to the nanoscopic domain. From a fundamental perspective, the interactions of water and solutes with a confining surface dramatically modify the liquid's structure and, consequently, both its thermodynamical and dynamical behaviors, breaking the validity of the classical thermodynamic and phenomenological description of the transport properties of aqueous systems. Additionally, man-made nanopores and porous materials have emerged as promising solutions to challenging problems such as water purification, biosensing, nanofluidic logic and gating, and energy storage and conversion, while aquaporin, ion channels, and nuclear pore complex nanopores regulate many biological functions such as the conduction of water, the generation of action potentials, and the storage of genetic material. In this work, the more recent experimental and molecular simulations advances in this exciting and rapidly evolving field will be reported and critically discussed.

Environmental chamber with controlled temperature and relative humidity for ice crystallization kinetic measurements by atomic force microscopy.

The present work describes the development of an environmental chamber (EC), with temperature and humidity control, for measuring ice growth kinetics over a substrate with an atomic force microscope (AFM). The main component of the EC is an AFM fluid glass cell. The relative humidity (RH) inside the EC is set by the flow of a controlled ratio of dry and humid nitrogen gases. The sample temperature is fixed with an AFM commercial accessory, while the temperature of the nitrogen gas inside the EC is controlled by circulating cold nitrogen vapor through a copper cooler, specially designed for this purpose. With this setup, we could study the growth rate of ice crystallization over a mica substrate by measuring the force exerted between the tip and the sample when they approach each other as a function of time. This experimental development represents a significant improvement with respect to previous experimental determinations of ice growth rates, where RH and temperature of the air above the sample were determined far away from the ice crystallization regions, in opposition to the present work.

Computational investigation of structure, dynamics and nucleation kinetics of a family of modified Stillinger-Weber model fluids in bulk and free-standing thin films.

In recent years, computer simulations have found increasingly widespread use as powerful tools for studying phase transitions in wide variety of systems. In the particular and very important case of aqueous systems, the commonly used force-fields tend to offer quite different predictions with respect to a wide range of thermodynamic and kinetic properties, including the ease of ice nucleation, the propensity to freeze at a vapor-liquid interface, and the existence of a liquid-liquid phase transition. It is thus of fundamental and practical interest to understand how different features of a given water model affect its thermodynamic and kinetic properties. In this work, we use the forward-flux sampling technique to study the crystallization kinetics of a family of modified Stillinger-Weber (SW) potentials with energy (ε) and length (σ) scales taken from the monoatomic water (mW) model, but with different tetrahedrality parameters (λ). By increasing λ from 21 to 24, we observe the nucleation rate increases by 48 orders of magnitude at a supercooling of ζ = T/Tm = 0.845. Using classical nucleation theory, we are able to demonstrate that this change can largely be accounted for by the increase in |Δµ|, the thermodynamic driving force. We also perform rate calculations in freestanding thin films of the supercooled liquid, and observe a crossover from surface-enhanced crystallization at λ = 21 to bulk-dominated crystallization for λ ≥ 22.

Diffusion-viscosity decoupling in supercooled glycerol aqueous solutions.

The diffusion of ferrocene methanol in supercooled glycerol-water mixtures has been measured over a wide viscosity range, which allowed analyzing the composition dependence of the Stokes-Einstein breakdown (diffusion-viscosity decoupling). The observed decoupling exhibits a common behavior for all studied compositions (glycerol mass fractions between 0.7 and 0.9), determined by the reduced temperature (T/Tg) of the mixtures. This result differs from that reported previously for the diffusion of glycerol in its aqueous solutions, where the reduced temperature for the decoupling decreases with increasing water content. We conclude that the contradictory results are only apparent, and they can be explained by the use of inconsistent extrapolated values of the viscosity of the glycerol-water mixtures in the supercooled region.

Concentration and temperature dependence of the viscosity of polyol aqueous solutions.

The concentration and temperature dependence of the viscosity of supercooled polyol (sucrose, trehalose, glucose and glycerol) aqueous solutions was analyzed with the aim of finding simple and accurate correlation equations for the description of this transport property. Three different equations were examined and compared, two empirical equations and an equation derived from the Avramov-Milchev (AM) model. If a description of the viscosity temperature dependence is intended, the AM model gives the best representation of the experimental data with only two adjustable parameters, which have a clear physical meaning. However, if we focus on both, temperature and concentration dependence, the empirical equations are found to be superior to the AM model, except for the glycerol aqueous system. The AM model includes a parameter related to the system fragility, which was obtained for all the aqueous polyol mixtures previously mentioned as a function of concentration, and also for water-trehalose-sodium tetraborate mixtures as a function of the electrolyte content. The results show that the fragility parameter increases with polyol concentration in the series glycerol

A 30-year epidemiologic survey (1974-2003) of haematological malignancies on the island of Sardinia: temporal changes in incidence and a geographic comparison of incidence rates.

In a previous survey of newly diagnosed haematological malignancies (HMs) in Sardinia from 1974 to 1993, we observed a marked increase in the incidence of many HMs that we chiefly attributed to improvements in case ascertainment. To better define the nature of this increase, we extended the survey by an additional decade (1994-2003), applying the same previously used methods. The incidence of HMs further increased from 1994 to 2003. The incidence rate of total HMs (THMs), standardised to the world population, was 30.15 × 10(5) person-years vs. 21.58 from 1984 to 1993 and 15.26 from 1974 to 1983. The temporal variations in the incidence differed in different HMs and were correlated with the diseases clinical characteristics and the increased availability of diagnostic tools and skills in Sardinia. These observations support the hypothesis that the temporal differences in the incidence rates observed for many HMs in Sardinia over the 30-year survey period were caused by temporal differences in diagnostic efficiency rather than by disease occurrence. An important exception was the increase in non-Hodgkin's lymphoma, which represents a true increase in occurrence, similarly to most Western countries. The incidence rates of HMs already having or reaching stable values in the decade 1994-2003 were similar to those of most Western countries. No significant evidence emerged to suggest that Sardinian particularities influenced the occurrence of HMs. This study demonstrates the extent to which diagnostic efficiency can influence incidence evaluations and emphasises the importance of prolonged observation to determine the validity of incidence rates for both temporal and geographic comparisons.

Excess protons in water-acetone mixtures. II. A conductivity study.

In the present work we complement a previous simulation study [R. Semino and D. Laria, J. Chem. Phys. 136, 194503 (2012)] on the disruption of the proton transfer mechanism in water by the addition of an aprotic solvent, such as acetone. We provide experimental measurements of the mobility of protons in aqueous-acetone mixtures in a wide composition range, for water molar fractions, xw, between 0.05 and 1.00. Furthermore, new molecular dynamics simulation results are presented for rich acetone mixtures, which provide further insight into the proton transport mechanism in water-non-protic solvent mixtures. The proton mobility was analyzed between xw 0.05 and 1.00 and compared to molecular dynamics simulation data. Results show two qualitative changes in the proton transport composition dependence at xw ∼ 0.25 and 0.8. At xw < 0.25 the ratio of the infinite dilution molar conductivities of HCl and LiCl, Λ(0)(HCl).Λ(0)(LiCl)(-1), is approximately constant and equal to one, since the proton diffusion is vehicular and equal to that of Li(+). At xw ∼ 0.25, proton mobility starts to differ from that of Li(+) indicating that above this concentration the Grotthuss transport mechanism starts to be possible. Molecular dynamics simulation results showed that at this threshold concentration the probability of interconversion between two Eigen structures starts to be non-negligible. At xw ∼ 0.8, the infinite molar conductivity of HCl concentration dependence qualitatively changes. This result is in excellent agreement with the analysis presented in the previous simulation work and it has been ascribed to the interchange of water and acetone molecules in the second solvation shell of the hydronium ion.

Unbalanced 1q whole-arm translocation resulting in der(14)t(1;14)(q11-12;p11) in myelodysplastic syndrome.

Unbalanced whole-arm translocations (WATs) of the long arm of chromosome 1, resulting in complete trisomy 1q, are chromosomal abnormalities detectable in both solid tumors and hematologic neoplasms. Among the WATs of 1q to acrocentric chromosomes, a few patients with der(1;15) described as a dicentric chromosome have been reported so far, whereas cases of der(1;14) are much rarer. We report on a case of der(1;14) detected as single anomaly in a patient with myelodysplastic syndrome. The aim of our work was to investigate the breakpoints of the (1;14) translocation leading to the der(1;14). Fluorescence in situ hybridization (FISH) experiments have been performed on chromosome preparations from bone marrow aspirate, using specific centromeric probes of both chromosomes, as well as a probe mapping to 1q11 band. FISH results showed that in our patient the derivative chromosome was monocentric with a unique centromere derived from chromosome 14. The breakpoints of the translocation were located in the short arm of chromosome 14 and in the long arm of chromosome 1, between the alphoid D1Z5 and the satellite II domains. The 1q breakpoint was within the pericentromeric region of chromosome 1, which is notoriously an unstable chromosomal region, involved in different chromosomal rearrangements.

Viscosity of supercooled aqueous glycerol solutions, validity of the Stokes-Einstein relationship, and implications for cryopreservation.

The viscosity of supercooled glycerol aqueous solutions, with glycerol mass fractions between 0.70 and 0.90, have been determined to confirm that the Avramov-Milchev equation describes very well the temperature dependence of the viscosity of the binary mixtures including the supercooled regime. On the contrary, it is shown that the free volume model of viscosity, with the parameters proposed in a recent work (He, Fowler, Toner, J. Appl. Phys. 100 (2006) 074702), overestimates the viscosity of the glycerol-rich mixtures at low temperatures by several orders of magnitude. Moreover, the free volume model for the water diffusion leads to predictions of the Stokes-Einstein product, which are incompatible with the experimental findings. We conclude that the use of these free volume models, with parameters obtained by fitting experimental data far from the supercooled and glassy regions, lead to incorrect predictions of the deterioration rates of biomolecules, overestimating their life times in these cryopreservation media.

Anomalies in supercooled NaCl aqueous solutions: a microscopic perspective.

In this work we studied the effect of NaCl on the thermodynamic and dynamic properties of supercooled water, for salt concentrations between 0.19 and 1.33 mol kg(-1), using molecular dynamic simulations for TIP5P∕E water model and ion parameters specially designed to be used in combination with this potential. We studied the isobaric heat capacity (C(p)) temperature dependence and observed a maximum in C(p), occurring at T(m), that moves to lower temperature values with increasing salt concentration. Many characteristic changes were observed at scaled temperature T∕T(m) ∼ 0.96, namely a minimum in the density of the system, a reduction of the slope of the number of hydrogen bonds vs. temperature, and a crossover from Vogel-Tamman-Fulcher to Arrhenius dynamics. Finally, at low temperatures we observed that water dynamics become heterogeneous with an apparently common relationship between the fraction of immobile molecules and T/T(m) for all studied systems.

Multiple laparotomic myomectomy during pregnancy: a case report.

The presence of uterine myomas during pregnancy is considered a risk factor for gestation and delivery. In literature, myomas are related to spontaneous abortion, bleeding, PPROM, preterm delivery, placenta previa, placental abruption, fetal malpresentations, mechanical dystocia and high incidence of cesarean section. Laparotomic myomectomy done during pregnancy is indicated when symptoms related to uterine myomas, as acute pelvic pain or gastroenteric or urinary symptoms, persist despite the pharmacological therapy. The purpose of this study is to show a successful surgical management of uterine myomas at 15.5 weeks of pregnancy, which allowed the continuation of gestation and a delivery without major complications.

Fractional Walden rule for electrolytes in supercooled disaccharide aqueous solutions.

The electrical conductivity of CsCl, KCl, Bu(4)NBr, and Bu(4)NI was studied in stable and supercooled (metastable) sucrose and trehalose aqueous solutions over a wide viscosity range. The results indicate that large positive deviations from the Walden rule occur in these systems due to the higher tendency of the ions to move in water-rich regions, as previously observed for NaCl and MgCl(2). The electrical molar conductivity viscosity dependence can be described with a fractional Walden rule (Lambdaeta(alpha) = constant), where alpha is a decoupling parameter which increases with ionic size and varies between 0.61 and 0.74 for all of the studied electrolytes. Using the electrical molar conductivity dependence of ion-ion interactions, an effective dielectric constant was calculated for a trehalose 39 wt% aqueous solution as a function of temperature. Above 278 K, the effective and the bulk solution dielectric constants are similar, but at lower temperatures, where the carbohydrate becomes less mobile than water, the effective dielectric constant approaches the dielectric constant of water. We also conclude that the solute-solvent dielectric friction contribution can be neglected, reinforcing the idea that the observed breakdown of the Walden rule is due to the existence of local microheterogeneities. The Walden plots for the studied ionic solutes show a decoupling similar to that found for the diffusion of water in the same solutions.

Secondary relaxations in supercooled and glassy sucrose-borate aqueous solutions.

The dielectric relaxation spectra of concentrated aqueous solutions of sucrose-borate mixtures have been measured in the supercooled and glassy regions in the frequency range of 40Hz to 2MHz. The secondary (beta) relaxation process was analyzed in the temperature range 183-233K at water contents between 20 and 30wt%. The relaxation times were obtained, and the activation energy of that process was calculated. In order to assess the effect of borate on the relaxation of disaccharide-water mixtures, we also studied the dielectric behavior of sucrose aqueous solutions in the same range of temperatures and water contents. Our findings support the view that, beyond a water content of approximately 20wt%, the secondary relaxation of water-sucrose and water-sucrose-borate mixtures adopts a universal character that can be explained in terms of a simple exponential function of the temperature scaled by the glass transition temperature (T(g)). The behavior observed for water-sucrose and water-sucrose-borate mixtures is compared with previous results obtained in other water-carbohydrate systems.

Two cases of chronic lymphoproliferative disorders in psoriatic patients treated with cyclosporine: hairy cell leukemia and Waldenstrom macroglobulinemia.

The real risk of lymphoproliferative disease in psoriatic patients has not yet been defined. Two explanations can be given for the occurrence of these malignancies: the broad immune activation typical of psoriasis and the administration of an immuno-suppressive treatment. A few studies describing the development of non Hodgkin lymphomas in psoriatic patients undergoing cyclosporine A have been published, but data about the occurrence of chronic lymphoproliferative disorders have never been reported. Here we describe the occurrence of hairy cell leukemia and Waldenstrom macroglobulinemia in two psoriatic patients treated with cyclosporine A. It remains unclear in our cases of chronic lymphoproliferative disease, as well as in the reported cases of psoriatic patients who develop lymphomas, whether psoriasis or the immunosuppressive treatment could play a role, although it is not possible to exclude a synergism between these factors.

Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia.

Several cases of spontaneous remission (SR) interrupting the invariably progressive course of untreated acute myeloblastic leukemia (AML) have been reported so far. We shall add to this series the hematological and cytogenetic SR occurring in a 72-yr-old man affected by AML following myelodysplastic syndrome. At diagnosis cytogenetic analysis showed the 48, xy, del (6) (p22-pter), +13, +14 karyotype. Owing to a lobar pneumonia, the chemotherapy was deferred and a broad spectrum antibiotic therapy was established. Supportive care included red cells and platelet transfusions and low-dose corticosteroid. Two months later, after the pneumonia had completely disappeared, a complete remission, lasting about 5 months, was documented on bone marrow morphological and cytogenetical examination, although some degree of myeloid dysplasia persisted. Possible mechanisms of the various SRs described during the course of AML are discussed with a review of the literature.

Effect of salts on the properties of aqueous sugar systems, in relation to biomaterial stabilization. 1. Water sorption behavior and ice crystallization/melting.

Trehalose and sucrose, two sugars that are involved in the protection of living organisms under extreme conditions, and their mixtures with salts were employed to prepare supercooled or freeze-dried glassy systems. The objective of the present work was to explore the effects of different salts on water sorption, glass transition temperature (T(g)), and formation and melting of ice in aqueous sugar systems. In the sugar-salt mixtures, water adsorption was higher than expected on the basis of the water uptake by each pure component. In systems with a reduced mass fraction of water (w less-than-or-equal 0.4), salts delayed water crystallization, probably due to ion-water interactions. In systems where > 0.6, water crystallization could be explained by the known colligative properties of the solutes. The glass transition temperature of the maximally concentrated matrix (T(g)') was decreased by the presence of salts. However, the actual T(g) values of the systems were not modified. Thus, the effect of salts on sorption behavior and formation of ice may reflect dynamic water-salt-sugar interactions which take place at a molecular level and are related to the charge/mass ratio of the cation present without affecting supramolecular or macroscopic properties.

Maximal gamma-globin expression in the compound heterozygous state for -175G gamma HPFH and beta degree 39 nonsense thalassaemia: a case study.

The -175 (T-->C) G gamma hereditary persistence of fetal haemoglobin is a very rare promoter mutation occurring in Caucasians as well as in African-Americans. Heterozygotes for this non-deletional HPFH show 20% HbF, mostly of G gamma type. We describe here a healthy Sardinian man who coinherited -175 (T-->C) G gamma HPFH with the beta-thalassaemia codon 39 nonsense mutation in trans; he showed 64% HbF, 100% of G gamma type. Although the beta-globin haplotype pattern (II/II) was indicative of the presence of the A gamma T allele on both chromosomes, the A gamma T expression was undetectable by HPLC even in red cell populations separated by age. The proband was, moreover, homozygous for the -4 bp deletion at position -225 to -222 of A gamma promoter which has recently been associated with decreased A gamma T globin expression. These findings suggest that this maximal overexpression of G gamma-globin probably reflects intensified stimulation of the mutated G gamma promoter in this hitherto undescribed genetic condition.

Frequency of delta+ 27-thalassaemia in Sardinians.

To determine the incidence of delta+ 27 thalassaemia in Northern Sardinia we examined blood samples from 750 Sardinian schoolboys by PCR-based molecular analysis. The incidence of delta+ 27 mutation was 1.2% in this study, i.e. twice as high as previously described on the basis of phenotypical studies; the frequency of the beta-thalassaemia is 10.5% and their interaction has been calculated at 0.0003. The majority of delta+ 27 carriers are characterized by a HbA2 level lower than 1.9% and the mean HbA2 level is significantly lower than in normal subjects. All compound heterozygotes for delta+ 27 and beta-thalassaemia show a silent beta-thalassaemic phenotype related to normalization of their HbA2 levels. This study suggests that delta+ 27 thalassaemia should be borne in mind in counselling at-risk couples in which one member has the typical high HbA2 beta-thal trait while the other shows normal or borderline HbA2 level. In these subjects, PCR-based ECO O 109 I digestion of the delta globin gene allows rapid detection of the delta+ 27 mutation.