Effects of degree correlations on the explosive synchronization of scale-free networks.

We study the organization of finite-size, large ensembles of phase oscillators networking via scale-free topologies in the presence of a positive correlation between the oscillators' natural frequencies and the network's degrees. Under those circumstances, abrupt transitions to synchronization are known to occur in growing scale-free networks, while the transition has a completely different nature for static random configurations preserving the same structure-dynamics correlation. We show that the further presence of degree-degree correlations in the network structure has important consequences on the nature of the phase transition characterizing the passage from the phase-incoherent to the phase-coherent network state. While high levels of positive and negative mixing consistently induce a second-order phase transition, moderate values of assortative mixing, such as those ubiquitously characterizing social networks in the real world, greatly enhance the irreversible nature of explosive synchronization in scale-free networks. The latter effect corresponds to a maximization of the area and of the width of the hysteretic loop that differentiates the forward and backward transitions to synchronization.

Effective centrality and explosive synchronization in complex networks.

Synchronization of networked oscillators is known to depend fundamentally on the interplay between the dynamics of the graph's units and the microscopic arrangement of the network's structure. We here propose an effective network whose topological properties reflect the interplay between the topology and dynamics of the original network. On that basis, we are able to introduce the effective centrality, a measure that quantifies the role and importance of each network's node in the synchronization process. In particular, in the context of explosive synchronization, we use such a measure to assess the propensity of a graph to sustain an irreversible transition to synchronization. We furthermore discuss a strategy to induce the explosive behavior in a generic network, by acting only upon a fraction of its nodes.

[Efficacy of parenteral glutamine in patients undergoing bone marrow transplantation]. / Eficacia de la glutamina parenteral en pacientes sometidos a trasplante autólogo de médula ósea.

INTRODUCTION: Autologous bone marrow transplant (ABMT) represents a high metabolic stress. Glutamine has proven to be effective in severe catabolic states, although there are controversial studies. OBJECTIVES: To assess the effect of parenteral nutrition (PN) therapy supplemented with glutamine on the occurrence of mucositis and mean hospital stay in patients submitted to ABMT. METHODS: Retrospective study of patients submitted to ABMT between 2006 and 2009. In 2008, one vial of L-alanyl-L-glutamine (20 g) was added by protocol to the PN formulations of these patients. Thirteen clinical charts since that date (glutamine group) and 13 previous charts (control group) were randomly selected (n = 26). We compared the degree of mucositis and hospital stay in both groups. In the subgroup of glutamine-treated patients, we compare the glutamine dose in the patients developing some degree of mucositis with that of those not having this complication. RESULTS: Mean hospital stay: 27.8 ± 7.4 days (control group) vs. 20.3 ± 5.3 days (glutamine group) (p = 0.01). The severity of mucositis was lower in the glutaminetreated group (p = 0.02). The weight-adjusted dose of L-alanyl-L-glutamine in the patients not developing mucositis was higher than in the other ones (0.32 vs. 0.24 g/kg/day; p = 0.02). CONCLUSIONS: Glutamine supplementation reduces the degree of mucositis and hospital stay in patients submitted to autologous bone marrow transplantation. The degree of mucositis is lower in the subgroup of patients receiving higher doses of glutamine.

Mechanical behaviour and rupture of normal and pathological human ascending aortic wall.

The mechanical properties of aortic wall, both healthy and pathological, are needed in order to develop and improve diagnostic and interventional criteria, and for the development of mechanical models to assess arterial integrity. This study focuses on the mechanical behaviour and rupture conditions of the human ascending aorta and its relationship with age and pathologies. Fresh ascending aortic specimens harvested from 23 healthy donors, 12 patients with bicuspid aortic valve (BAV) and 14 with aneurysm were tensile-tested in vitro under physiological conditions. Tensile strength, stretch at failure and elbow stress were measured. The obtained results showed that age causes a major reduction in the mechanical parameters of healthy ascending aortic tissue, and that no significant differences are found between the mechanical strength of aneurysmal or BAV aortic specimens and the corresponding age-matched control group. The physiological level of the stress in the circumferential direction was also computed to assess the physiological operation range of healthy and diseased ascending aortas. The mean physiological wall stress acting on pathologic aortas was found to be far from rupture, with factors of safety (defined as the ratio of tensile strength to the mean wall stress) larger than six. In contrast, the physiological operation of pathologic vessels lays in the stiff part of the response curve, losing part of its function of damping the pressure waves from the heart.

Eficacia de la glutamina parenteral en pacientes sometidos a trasplante autólogo de médula ósea / Efficacy of parenteral glutamine in patients undergoing bone marrow transplantation

Introducción: El Trasplante Autólogo de Médula Ósea(TASPE) conlleva un alto estrés metabólico. La glutamina es considerada se ha mostrado eficaz en estados catabólicos severos, aunque hay estudios contradictorios. Objetivos: Valorar el efecto del tratamiento con nutrición parenteral (NP) suplementada con glutamina en el desarrollo de mucositis y en la estancia media hospitalaria en pacientes sometidos a TASPE. Metodología: Estudio retrospectivo de pacientes con TASPE efectuados entre 2006 y 2009. En 2008 se introdujo de forma protocolizada la adición de 1 vial de L-alanil-L-glutamina (20 g) en las fórmulas de NP de dichos pacientes. Se seleccionaron aleatoriamente 13 historias apartir de dicha fecha (grupo glutamina) y 13 historias anteriores (grupo control) (n = 26). Se comparó el grado de mucositis y la estancia hospitalaria en los dos grupos. En el subgrupo de pacientes tratados con glutamina, se comparó la dosis de glutamina que recibieron los pacientes que desarrollaron algún grado mucositis con aquellos que no presentaron dicha complicación. Resultados: Estancia media: 27,8 ± 7,4 días (grupo control) vs 20,3 ± 5,3 días (grupo glutamina) (p = 0,01). La gravedad de la mucositis fue menor en el grupo glutamina (p = 0,02). La dosis de L-alanail-L-glutamina ajustada por peso en los pacientes que no desarrollaron mucositis fue mayor que en los que la desarrollaron (0,32 vs 0,24g/kg/día; p = 0,02).Conclusiones: La suplementación con glutamina reduce el grado de mucositis y la estancia hospitalaria en pacientes sometidos a transplante autólogo de médula ósea. El grado de mucositis es menor en el subgrupo de pacientes que reciben dosis más elevadas de glutamina (AU)

Introduction: Autologous bone marrow transplant(ABMT) represents a high metabolic stress. Glutamine has proven to be effective in severe catabolic states, although there are controversial studies. Objectives: To assess the effect of parenteral nutrition(PN) therapy supplemented with glutamine on the occurrence of mucositis and mean hospital stay in patients submitted to ABMT. Methods: Retrospective study of patients submitted to ABMT between 2006 and 2009. In 2008, one vial of Lalanyl-L-glutamine (20 g) was added by protocol to the PN formulations of these patients. Thirteen clinical charts since that date (glutamine group) and 13 previous charts (control group) were randomly selected (n = 26).We compared the degree of mucositis and hospital stay in both groups. In the subgroup of glutamine-treated patients, we compare the glutamine dose in the patients developing some degree of mucositis with that of those not having this complication. Results: Mean hospital stay: 27.8 ± 7.4 days (control group) vs. 20.3 ± 5.3 days (glutamine group) (p = 0.01).The severity of mucositis was lower in the glutamine treated group (p = 0.02). The weight-adjusted dose of Lalanyl-L-glutamine in the patients not developing mucositis was higher than in the other ones (0.32 vs. 0.24g/kg/day; p = 0.02). Conclusions: Glutamine supplementation reduces the degree of mucositis and hospital stay in patients submitted to autologous bone marrow transplantation. The degree of mucositis is lower in the subgroup of patients receiving higher doses of glutamine (AU)

Response of human coronary arteries at different mechanical conditions.

The lack of reliable mechanical data on coronary arteries hampers the application of numerical models to vascular problems, and precludes physicians from knowing in advance the response of coronary arteries to the different interventions. In this work, the mechanical properties of human coronary arteries have been characterized. Whole samples from human right (RC) and left anterior descending (LAD) coronary arteries aged between 23 and 83 years have been studied by means of in-vitro tensile testing up to failure. Knowledge of the mechanical response of human coronary arteries could be applied to optimize the election of vascular grafts or to prevent arterial damage during angioplasty.

Mechanical properties of human coronary arteries.

The lack of reliable mechanical data on coronary arteries and, more specifically, on their wall strength hampers the application of numerical models and simulations to vascular problems, and precludes physicians from knowing in advance the response of coronary arteries to the different interventions. Studies of the mechanical properties of coronary arteries have been carried out almost exclusively on animals. Only a few studies have tried to characterize the in vivo behavior of human coronaries through tests under physiological conditions. In this work, the mechanical properties of human coronary arteries have been characterized. Whole samples from human right (RC) and left anterior descending (LAD) coronary arteries aged between 23 and 83 years have been studied by means of in-vitro tensile testing up to failure.

Association between mechanics and structure in arteries and veins: theoretical approach to vascular graft confection.

Biomechanical and functional properties of tissue engineered vascular grafts must be similar to those observed in native vessels. This supposes a complete mechanical and structural characterization of the blood vessels. To this end, static and dynamic mechanical tests performed in the sheep thoracic and abdominal aorta and the cava vein were contrasted with histological quantification of their main constituents: elastin, collagen and muscle cells. Our results demonstrate that in order to obtain adequate engineered vascular grafts, the absolute amount of collagen fibers, the collagen/elastin ratio, the amount of muscle cells and the muscle cells/elastic fibers ratio are necessary to be determined in order to ensure adequate elastic modulus capable of resisting high stretches, an adequate elastic modulus at low and normal stretch values, the correct viscous energy dissipation, and a good dissipation factor and buffering function, respectively.

Effect of atherosclerosis on thermo-mechanical properties of arterial wall and its repercussion on plaque instability.

Data from the literature report febrile reactions prior to myocardial infarction in patients with normal coronary arteries and that coronary syndromes seem to be triggered by bacterial and viral infections, being fever the common symptom. The thermo-mechanical behavior of thoracic aortas of New Zealand White rabbits with different degrees of atherosclerosis was measured by means of pressure-diameter tests at different temperatures. Specific measurements of the thermal dilatation coefficient of atheroma plaques were performed by means of tensile tests. Results show a different thermo-mechanical behavior, the dilatation coefficient of atheroma plaque being at least twice that of the arterial wall. Temperature-induced mechanical stress at the plaque-vessel interface could be enough to promote plaque rupture. Therefore, increases of corporal temperature, either local or systemic, can play a role in increasing the risk of acute coronary syndromes and deserve a more comprehensive study.

Arterial complex elastic modulus was preserved after an intercontinental cryoconserved exchange.

There is a pressing need to obtain adequate vascular substitutes for arterial by-pass or reconstruction. Since the performance of venous and commercially prosthetic grafts is not ideal and the availability of autologous arteries is limited, the use of cryopreserved arteries has emerged as a very attractive alternative. In this sense, the development of an inter-continental network for cryopreserved tissue exchange would improve international cooperation increasing the possibilities of obtaining the requested materials. In this work, the effects of an inter-continental shipment, which includes cryopreservation, on the biomechanical properties of sheep aortas were evaluated by means of the arterial complex elastic modulus. It is shown that these properties were preserved after the shipment. The actual possibilities of establishing a network for arterial exchange for the international cooperation are discussed.

Comparison of an acetonitrile extraction/partitioning and "dispersive solid-phase extraction" method with classical multi-residue methods for the extraction of herbicide residues in barley samples.

An acetonitrile/partitioning extraction and "dispersive solid-phase extraction (SPE)" method that provides high quality results with a minimum number of steps and a low solvent and glassware consumption was published in 2003. This method, suitable for the analysis of multiple classes of pesticide residues in foods, has been given an acronymic name, QuEChERS, that reflects its major advantages (quick, easy, cheap, effective, rugged, safe). In this work, QuEChERS method, which was originally created for vegetable samples with a high amount of water, was modified to optimise the extraction of a wide range of herbicides in barley. Then, it was compared with known conventional multi-residue extraction procedures such as the Luke method, which was simplified and shortened by eliminating the Florisil clean-up (mini Luke) and the ethyl acetate extraction, which involves a subsequent clean-up by gel permeation chromatography (GPC) and which is the official extraction method used by some of European authorities. Finally, a simple acetone extraction was carried out to check the differences with the other three methods. Extracts were analysed by gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mini Luke was significantly more effective for the extraction of non-polar and medium-polar compounds, but the best recoveries for polar compounds were achieved by QuEChERS and ethyl acetate methods. QuEChERS was the only method that provided an overall recovery value of 60-70% for non-, medium- and polar compounds, with some exceptions due to co-eluted matrix interferences. Clean-up by dispersive SPE was effective and did not differ so much with ethyl acetate extracts considering that QuEChERS clean-up step is much easier and less time-consuming. As a conclusion, it resulted to be the most universal extraction method by providing a well-defined phase separation without dilution and achieving acceptable recoveries in average including the extraction of the always difficult acidic herbicides. However, recoveries were not as good as required for validation purposes suggesting that residues are prone to strong matrix interactions in dry samples as barley and further method adaptation incrementing solvent strength, extraction time or more acidic or basic conditions is needed in order to achieve a complete extraction.

Study of different parameters affecting the derivatization of acidic herbicides with trimethylsulfonium hydroxide to make them suitable for gas chromatography analysis.

In this study, an orthogonal array design was applied to know the way different parameters affected the derivatization of some herbicides that are commonly applied in the soils. Herbicides formulated as esters have been reported to rapidly hydrolyse, in contact with soil, to their corresponding acids and phenols. What involves is that both forms need to be monitored. Acidic herbicides and phenols cannot be detected by gas chromatography (GC) due to their polarity and low volatility that cause peak asymmetry. Therefore, masking of these polar groups by eliminating the active hydrogen atom with derivatization to their corresponding esters/ethers is needed in order to yield products that possess enhanced volatility and improved GC properties. A lot of derivatization reagents have been proposed but trimethylsulfonium hydroxide (TMSH) was selected due to its easy and quantitative formation of methyl esters/ethers. It was observed that the addition of TMSH promoted not only esterification of acids/phenols but trans-esterification of the original non-hydrolyzed remaining esters to their corresponding methyl ones. As a result, methyl esters/ethers were the final product of both reactions. Different parameters were studied in the statistical design for both TMSH promoted reactions: type of solvent, pH, temperature and time of incubation. The amount of derivatization reagent was calculated to be high enough to ensure the complete derivatization of all compounds present in the sample. The reaction medium was shown as an important factor. The formation of some methyl esters/ethers decreased with increasing time and temperature because trans-esterification, being an equilibrium where the formation of smaller structures is promoted, was not enough shifted. However, the statistical analysis revealed that only the pH of the solution played an important role during the derivatization process. The presence of the anionic form of the acids appeared to be essential for derivatization, being diminished in strong acidic conditions. In addition, pre-heating was shown not to improve derivatization reaction, being easily carried on in the injector port of the GC system.

Decreased susceptibility to oxidative stress underlies the resistance of specific dopaminergic cell populations to paraquat-induced degeneration.

The vulnerability of different dopaminergic cell populations to damage caused by the herbicide paraquat was assessed by stereological counts of tyrosine hydroxylase-positive and calbindin-D28k-immunoreactive neurons in A9 (substantia nigra pars compacta) and A10 (ventral tegmental area and other cell groups). In saline-treated control mice, tyrosine hydroxylase-immunoreactive neurons represented 80% and 45% of the total neuronal population in A9 and A10, respectively, and the number of calbindin-D28k-positive neurons was five times greater in A10 than A9. Sequential injections with paraquat resulted in a significant loss of dopaminergic neurons in A9. In contrast, tyrosine hydroxylase-positive cells in A10 were spared from paraquat-induced degeneration. Furthermore, expression of calbindin-D28k was consistently associated with neuronal resistance to the herbicide in both A9 and A10. Paraquat exposure also induced oxidative stress as indicated by an increase in the number of midbrain cells positive for 4-hydroxy-2-nonenal, a marker of lipid peroxidation. Co-localization studies revealed that calbindin-D28k immunoreactivity overlapped with tyrosine hydroxylase labeling and that, after paraquat administration, (i) the vast majority of midbrain 4-hydroxy-2-nonenal-immunoreactive cells were dopaminergic (tyrosine hydroxylase-immunoreactive), (ii) tyrosine hydroxylase/4-hydroxy-2-nonenal-positive neurons were much more prevalent in A9 than A10, and (iii) all calbindin-D28k-containing neurons were characterized by lack of lipid peroxidation (4-hydroxy-2-nonenal immunoreactivity). Results in this paraquat model emphasize that, despite sharing a similar dopaminergic phenotype, different groups of midbrain neurons vary dramatically in their vulnerability to injury. Data also indicate that these differences are attributable, at least in part, to a varying susceptibility of dopaminergic cell populations to oxidative stress.

Thermomechanical behavior of human carotid arteries in the passive state.

Localized heating or cooling is expanding the clinical procedures used to treat cardiovascular diseases. Advantageous implementation and development of these methods are linked indissolubly to a deeper understanding of the arterial response to combined mechanical and thermal loads. Despite this, the basic thermomechanical behavior of human blood vessels still remains largely unknown, primarily due to the lack of appropriate experimental data. In this work, the influence of temperature on the passive behavior of human carotid arteries was studied in vitro by means of inflation tests. Eleven carotid segments were tested in the range 0-200 mmHg at four different temperatures of 17, 27, 37, and 42 degrees C. The results show that the combined change of temperature and stress has a dramatic effect on the dilatation coefficient of the arterial wall, which is shifted from negative to positive depending on the stress state, whereas the structural stiffness of the arterial wall does not change appreciably in the range of temperatures tested.

Volatilisation of triallate as affected by soil texture and air velocity.

The rate of volatilisation of the formulated herbicide triallate was investigated in a wind tunnel under controlled wind-speed conditions. An experimental set-up is described which allows the monitoring of wind speed (w.s.), soil-water content, and the temperature of air and soil. A system controlling soil-water content is also described. The influence of air velocity and soil texture was investigated measuring the cumulative volatilisation losses of triallate from soil. The herbicide volatilisation losses after application ranged from 40% at 3 m/s to 53% at 9 m/s for loam soil and from 60% at 3 m/s to 73% at 9 m/s for sandy soil.

Adhesive events in retinal development and function: the role of integrin receptors.

Cells in the developing retina contact a vast array of molecular cues in their microenvironment that are thought to guide their development. Many of these cues are embedded in the surface of neighboring cells or deposited within the extracellular matrix (ECM). Evidence has accumulated that cell-cell and cell-ECM interactions are essential in many phases of neural development, including neuroblast migration, determination of cell fate, axon outgrowth and synapse formation. In this chapter, we examine the developmental and functional roles fulfilled by integrins, a family of receptors for ECM molecules and cell adhesion molecules (CAMs). We have approached this problem by addressing a series of three questions: (1) which integrins are expressed in developing retina? (2) when and where are they expressed? and, (3) what functions do they carry out? Integrins have previously been implicated in axon extension, but new evidence suggests that they are also involved in earlier developmental events in preaxonal neuroblasts. High levels of expression of at least eight integrin subunits have been documented in these young retinal cells, and integrins containing the beta 1 subunit have been implicated in migration of adolescent retinal ganglion cells. Integrin expression persists through adulthood, both in the retina and in the neighboring layer of the retinal pigment epithelium (RPE). The integrin alpha v beta 5 has been shown to reside on the apical surface of the RPE and has been implicated in the phagocytosis of shed photoreceptor outer segments.

Human ERK1 induces filamentous growth and cell wall remodeling pathways in Saccharomyces cerevisiae.

Expression of an activated extracellular signal-regulated kinase 1 (ERK1) construct in yeast cells was used to examine the conservation of function among mitogen-activated protein (MAP) kinases. Sequence alignment of the human MAP kinase ERK1 with all Saccharomyces cerevisiae kinases reveals a particularly strong kinship with Kss1p (invasive growth promoting MAP kinase), Fus3p (pheromone response MAP/ERK kinase), and Mpk1p (cell wall remodeling MAP kinase). A fusion protein of constitutively active human MAP/ERK kinase 1 (MEK) and human ERK1 was introduced under regulated expression into yeast cells. The fusion protein (MEK/ERK) induced a filamentation response element promoter and led to a growth retardation effect concomitant with a morphological change resulting in elongated cells, bipolar budding, and multicell chains. Induction of filamentous growth was also observed for diploid cells following MEK/ERK expression in liquid culture. Neither haploids nor diploids, however, showed marked penetration of agar medium. These effects could be triggered by either moderate MEK/ERK expression at 37 degrees C or by high level MEK/ERK expression at 30 degrees C. The combination of high level MEK/ERK expression and 37 degrees C resulted in cell death. The deleterious effects of MEK/ERK expression and high temperature were significantly mitigated by 1 m sorbitol, which also enhanced the filamentous phenotype. MEK/ERK was able to constitutively activate a cell wall maintenance reporter gene, suggesting misregulation of this pathway. In contrast, MEK/ERK effectively blocked expression from a pheromone-responsive element promoter and inhibited mating. These results are consistent with MEK/ERK promoting filamentous growth and altering the cell wall through its ability to partially mimic Kss1p and stimulate a pathway normally controlled by Mpk1p, while appearing to inhibit the normal functioning of the structurally related yeast MAP kinase Fus3p.

Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids.

Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis.

Identification of inhibitor specificity determinants in a mammalian phosphodiesterase.

Mammalian phosphodiesterase types 3 and 4 (PDE3 and PDE4) hydrolyze cAMP and are essential for the regulation of this intracellular second messenger in many cell types. Whereas these enzymes share structural and biochemical similarities, each can be distinguished by its sensitivity to isozyme-specific inhibitors. By using a series of chimeric enzymes, we have localized the region of PDE4 that confers sensitivity to selective inhibitors. This inhibitor specificity domain lies within a short sequence at the carboxyl terminus of the catalytic domain of the protein, consistent with the competitive nature of inhibition by these compounds. Surprisingly, the identified region also includes some of the most highly conserved residues among PDE isoforms. A yeast-based expression system was used for the isolation and characterization of mutations within this area that confer resistance to the PDE4-specific inhibitor rolipram. Analysis of these mutants indicated that both conserved and unique residues are required for isoform-specific inhibitor sensitivity. In some cases, combined point mutations contribute synergistically to the reduction of sensitivity (suppression of IC50). We also report that several mutations display differential sensitivity changes with respect to distinct structural classes of inhibitors.