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Diagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs.A total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE).Compared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p 0.001) and aortic root size (p 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups.Our results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.

We present numerical simulations, based on a CFD–DEM approach, of the transport and settlement of proppant in a planar vertical cell that mimics a hydraulic fracture. These simulations, with resolution at the particle level, allow for a clean measurement of the dune placement and proppant degree of mixing. The effect of the position of the injection points is considered by three different injection heights in the vertical cell. Different proppant injection strategies were also considered by using two different proppant types that can be injected in different orders or simultaneously as a mixture. We evaluate the position and shape of the settled dune. We measure the degree of mixing of the two proppant types by using the concept of mixing entropy. We have found that an injection point placed close to the bottom of the cell leads to a dune close to the injection points, and that an injection point at the middle or at the top of the cell leads to a rather flat dune. Injecting different proppant types in different orders yields distinctive proppant distributions. This helps in evaluating the benefits of positioning perforation clusters close to geological boundaries that favor fracture growth in the upward or downward direction as well as selecting the order of proppant mesh injection. All the simulations correspond to the early stage, before the “traction carpet” effect comes into play Fil: Baldini, Mauro. Universidad Tecnológica Nacional; Argentina Fil: Carlevaro, Carlos Manuel. YPF - Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina Fil: Pugnaloni, Luis Ariel. Universidad Tecnológica Nacional; Argentina Fil: Sánchez, Martín. Universidad Tecnológica Nacional; Argentina

The multicellular behavior designated “red dry and rough” (rdar) morphotype—characterized by production of extracellular matrix mainly comprising curli fimbriae and cellulose—is a potential survival strategy of Escherichia coli outside the host. This study documents the ability of Escherichia cryptic clades, which have recently been recognized as new lineages genetically divergent from E. coli , to grow in unfavorable conditions through expression of distinct phenotypes. Growth under low-temperature and nutrient-poor conditions induced the rdar morphotype in all cryptic clade strains tested, especially after preincubation in broth supplemented with uracil. Such phenotypic response to harsh growth conditions was clearly detected by transmission and scanning electron microscopy, which showed that bacteria were encased in a fibrous matrix. Conversely, cells incubated in rich medium at 37 °C showed no matrix. Uracil enhanced the biosynthesis of matrix components, fostering biofilm production and strain adhesion to abiotic surfaces, as demonstrated by the increase of strong biofilm producers in biofilm assays. Harsh growth conditions also induced catalase activity, resulting in clade strain resistance to hydrogen peroxide oxidative stress. The present findings further support the ‘environmental hypothesis’ whereby cryptic clades would be able to persist in natural habitats outside the host through the expression of distinct survival phenotypes.

In recent years, there has been a number of experimental and numerical studies on the transport and settlement of proppant in scaled laboratory fractures that are of interest to understand hydraulic stimulation in hydrocarbon reservoirs. The results from these studies are generally taken with skepticism by the industry. Part of this is due to the perception that results must be very sensitive to the boundary conditions. Small changes in the experimental configuration are expected to lead to very different results. In particular, little is known on how the actual roughness of the fracture walls and the way the slurry is drained from the laboratory cell affect the results. Here, we report experimental results on the proppant transport in a scaled vertical rough cell that mimics a vertical fracture induced during stimulation. We compare results with those obtained in a smooth wall cell, which is more common in laboratory tests. We found that a rough wall allows for a significant increase in the amount of proppant deposited in the cell at high pumping rate. However, the effect of roughness seems to be marginal for low pumping rates, suggesting that most previous studies in the literature which use of a reduced pumping rate were not significantly affected by the use of smooth walls. We also designed different flow configurations at the fracture tip (where the slurry drains form the cell) to study their effect on the way in which the proppant is deposited in the fracture. We found that, in general, the deposited dune is fairly independent of the particular boundary conditions. This suggests that most results reported in the literature are also robust against changes in the selected outflow configuration.

Epidemiological evidence from observational studies suggests that dietary polyphenols (PPs) – phytochemicals found in a variety of plant-based foods – can reduce the risk of developing type 2 diabetes mellitus (T2DM). Clinical trials have also indicated that PPs may help manage the two key features of T2DM, hyperglycemia and dyslipidemia. Since the incidence of T2DM is dramatically increasing worldwide, identifying food-based approaches that can reduce the risk of developing it and help manage its main risk factors in early-stage disease has clinical and socioeconomic relevance. After a brief overview of current epidemiological data on the incidence of T2DM in individuals consuming PP-rich diets, we review the evidence from clinical trials investigating PP-enriched foods and/or PP-based nutraceutical compounds, report their main results, and highlight the knowledge gaps that should be bridged to enhance our understanding of the role of PPs in T2DM development and management.

We present simulations using a coupled Computational Fluid Dynamics–Discrete Element Method (CFD–DEM) approach for a slurry of millimeter-sized particles in water which is squeezed between two walls and then made flow out though a narrow aperture. The process is akin to the flowback stage in the near wellbore zone of a hydraulic-stimulated well for hydrocarbon recovery. We consider different wall roughness and investigate its effect on particle production, final distance between walls, spatial particle distribution between the walls, and fluid production rate. We have found that the final distribution of particles changes significantly with small variations in the roughnesses of the walls. This in turn leads to production flow rates that may vary up to 50%. Although the main driver of the production for unconventional wells is the propped fracture network, these results suggest that the roughness of the fracture walls seems to play an important role in the final conductivity and therefore in the ultimate recovery.

Particle Image Velocimetry (PIV) is a well established technique used to measure displacements in fluids. Proppant transport and placement is a crucial phase in the process of well completion to stimulate production in gas and oil reservoirs. Proppant (a granular material) is injected along fluids during hydraulic stimulation to prop fractures open after hydrocarbon production is initiated. This work presents results on the use of PIV for the study of the transport of proppant in a large laboratory scale flat vertical fracture. Velocity and vorticity profiles were analyzed for different flow rates during the transport and settlement of the proppant inside the fracture. High flow rates, compatible with field operations are achieved in this setup. The results indicate that vortexes are present in a large portion of the system and that a non-linear interplay between the settling dune and the main vortex seems to determine the time at which a fast dune growth occurs in the fracture.

We consider the flow of disks of diameter d driven by a conveyor belt of dynamic friction coefficient μ through an aperture on a flat barrier. The flow rate presents two distinct regimes. At low belt velocities v the flow rate is proportional to v and to the aperture width A. However, beyond a critical velocity, the flow rate becomes independent of v and proportional to (A-kd)3/2 in correspondence with a two-dimensional Beverloo scaling. In this high-velocity regime we also show that the flow rate is proportional to μ1/2. We discuss that these contrasting behaviors arise from the competition between two characteristic time scales: the typical time a disk takes to stop on the belt after detaching from the granular pack and the time it takes to reach the aperture. Fil: Cordero, Manuel J.. Universidad Tecnológica Nacional; Argentina Fil: Pugnaloni, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional; Argentina

The goal of this paper is to share experience about the degradation assessment of railway track point machines. A real scale point machine test bench was used to perform several thousands of maneuvers. Recorded data consisted in the measurements of the shaft speed and the torque during a maneuver. Some faulty conditions were introduced to obtain degraded signals. Relevant indicators were computed to quantify the health state of the point machine and to detect faulty behaviours. The analysis also highlighted the influence of the temperature on the point machine performance. A degradation model is then built from the indicator to compute the reliability and the remaining useful life. The conclusions of this analysis will be useful to properly define an experimental design to be applied on a real turnout.

Alzheimer's disease (AD) is the most common cause of dementia accounting for 60-70% of all demented cases and one of the leading sources of morbidity and mortality in the aging population. Most of the recent literature regards the relationship between plasma oxidative stress and AD, showing that markers of lipid peroxidation are significantly higher in AD and Mild Cognitive Impairment (MCI) patients with respect to control subjects. The increased generation of reactive oxygen species that occurs in AD may be also responsible for oxidative injury to erythrocyte membranes. Since erythrocyte membrane serves as a variable barrier to oxygen transport, changes in its stability can induce cellular hypoxia and the consequence brain tissue oxygenation. In this study, plasma oxygen radical absorbance capacity (ORAC) and erythrocyte membrane fluidity have been evaluated in control, MCI and AD patients. Moreover erythrocyte membrane acetylcholinesterase (AchE) activity has been measured in control and AD patients. Plasma ORAC significantly decreased in MCI and AD subjects with respect to the controls, while a decrease in erythrocyte membrane fluidity has been observed only in MCI patients. No significant differences were detected in erythrocyte AchE activity between control subjects and AD patients.

The distribution, colocalization with enzymes producing nitric oxide (NO), and the synaptic organization of neurons containing two calcium-binding proteins (CaBPs) – parvalbumin (Parv) and calbindin-D28K (Calb) – were investigated in the rat periaqueductal gray matter (PAG). Parv-immunopositive (ParvIP) neurons were detected in the mesencephalic nucleus and rarely in the PAG. CalbIP neurons were found both in the dorsolateral (PAG-dl) and ventrolateral PAG (PAG-vl); their size ranged from 112.96 μm2 (PAG-dl) to 125.13 μm2 (PAG-vl). Ultrastructurally Parv and Calb immunoreactivity was mostly found in dendritic profiles. Axon terminals containing each of the two CaBPs formed symmetric synapses. Moreover both Parv and Calb were used to label a subpopulation of NO-producing neurons. Colocalization was investigated using two protocols: (i) a combination of Calb and Parv immunocytochemistry (Icc) with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry (Hi) and (ii) neuronal NO synthase-Icc (nNOS) (immunofluorescence). Both techniques demonstrated a complete lack of colocalization of Parv and NADPH-d/nNOS in PAG neurons. Double-labeled (DL) neurons (Calb-NADPH-d; Calb-nNOS) were detected in PAG-dl. NADPH-d-Hi/Calb-Icc indicated that 41–47% of NADPH-d-positive neurons contained Calb, whereas 17–23% of CalbIP cells contained NADPH-d. Two-color immunofluorescence revealed that 53–66% of nNOSIP cells colocalized with Calb and 24–34% of CalbIP neurons contained nNOS. DL neuron size was 104.44 μm2; neurons labeled only with NADPH-d or Calb measured 89.793 μm2 and 113.48 μm2, respectively. Together with previous findings ( Barbaresi et al. [2012] ) these data suggest that: (i) PAG-dl and PAG-vl contain fast CaBPs, (ii) a high degree of heterogeneity exists in PAG-dl, (iii) two subpopulations of NO-producing neurons containing distinct CaBPs are found in PAG-dl. Therefore the important aspect of the PAG intrinsic organization emerging from this and previous double-labeling studies is the chemical diversity of NO-synthesizing neurons, which is likely related to the different functions in which these neurons are involved.

Asbestos fibres can be transformed into potentially non-hazardous silicates by high-temperature treatment via complete solid-state transformation. A549 cells were exposed to standard concentrations of raw cement asbestos (RCA), chrysotile and cement asbestos subjected to an industrial process at 1200 degrees C (Cry_1200 and KRY.AS, respectively), raw commercial grey cement (GC). Cell growth rate and viability (MTT test) were detected in vitro. RCA and KRY.AS subjected to comprehensive microstructural study by electron microscopy were further in vitro assayed to compare their cytotoxic potential by morphostructural studies, proliferation index (Ki-67 antigen), apoptosis induction (AO/EB staining) assays and detection of intracellular reactive oxygen species (ROS) with the fluorescent DCFA dye. More severe cytotoxic damage was induced by RCA than by KRY.AS after each incubation period. Exposure to KRY.AS and GC resulted in comparable cell growth rates and cytotoxic effects. Cells incubated with RCA showed greater apoptotic induction and ROS production and a lower cell proliferation index than those exposed to KRY.AS. Chrysotile asbestos and RCA subjected to heat treatment underwent complete microstructure transformation. The final product of heat treatment of cement asbestos, KRY.AS, was considerably more inert and had lower cytotoxic potential than the original asbestos material in all in vitro tests.

This work applied a probe tensile separation method for quantitative characterisation of the stickiness of fluid foods and investigated its correlation to consumers’ sensory perception. Altogether 12 commercial fluid food products were tested. The maximum tensile force ( F m ) and the work till the maximum force ( W m ) were found to be useful parameters for stickiness prediction. Both of the parameters showed positive correlations with the results from sensory perception tests. It was found that, for some fluids, the total work done over the whole tensile separation ( W ) showed great discrepancy with the sensory perception, due to the existence of long force tail. The separation tests were performed over a wide range of probe speed (from 0.1 mm/s to 40 mm/s), but the inertial effect was found to be negligible. It was also demonstrated that, although the absolute value of force and work were highly dependent on the separation speed, the relative stickiness of foods was not affected as far as the tests were conducted under the same experimental setup. Possible mechanisms governing food stickiness were discussed. It was believed that pressure drop and cavitation of a suddenly stretched fluid could be critical in influencing consumers’ sensual perception of food stickiness.

Extensive research works have been carried out in investigating the microstructure of heat-set whey protein gels and their fractal nature, but little has been done on the surface studies of these systems due to the lack of suitable technique for surface characterization of wet and deformable food gels. This work intended to explore the possibility of applying confocal laser scanning microscope (CLSM) for surface characterization of such delicate systems. Surfaces of heat-set whey protein gels (14 wt%) have been investigated with and without the presence of salt (0 and 200 mM NaCl). High quality surface images across X–Z plane were obtained. These images were further analysed for their surface roughness, periodic length scale, and fractal nature. The roughness of these surfaces was quantified in terms of root-mean-square surface roughness (Rq) and arithmetic surface roughness (Ra). It was found that the protein gel without salt addition had a very smooth surface with Rq of 0.20 and 0.18 μm, respectively, but the gel containing 200 mM NaCl had a much rougher surface with large Rq and Ra (2.39 and 1.91 μm, respectively). The fractal nature of the surface was also revealed for this gel and a fractal dimension of 1.15 was obtained.

We present Brownian dynamics simulations of the compression and expansion of monolayers adsorbed at a planar interface. The surface-active species are modelled as monodisperse spherical particles that can form particle-particle elastic bonds. The objective is to model the large compression and expansion of viscoelastic protein films investigated in Langmuir trough experiments. We determine the stress-strain response of the system and the associated microstructural changes induced by the large deformation of the interface as a function of particle adsorption energy, and bond breakability and stiffness. We also study the effect of the velocity of compression and the type of compression (uniaxial or homogeneous) on the mechanism of collapse of the adsorbed films. Furthermore, we present simulations on complex mixed systems containing both bond-forming particles (modelling protein) and nonbond-forming particles (modelling surfactant). We find that the preferential desorption of one type of particle or the other, upon compression, is sensitive to the extent of bond breakability of the bond-forming species.

Water safety is an important quality objective, and special attention needs to be devoted to the pipes in which it runs. Rubber is one of the most widely used materials for drinking-water pipes. The various types of rubber are mixes often with vulcanising agents added to improve mechanical properties. The present study was conducted to evaluate and compare the behaviour of three currently used elastomer prototype mixes devised for use as water pipes before and after an artificial ageing procedure. Contact surface with the water was determined and “quality”-tested using SEM, AFM, FT-IR and biological (biocompatibility and bacterial adhesion) analyses. Differences in rubber composition between the native mixes were shown using FT-IR. Photo-ageing induced degradation of the surface film and in some cases gave rise to alkene derivatives with a small carbonyl component. Comparison of chemical, morphological and biological data before and after photo-ageing highlights the risk to which pipes are exposed over time even in the absence of specific chemico-physical insults.

Proteins and low-molecular-weight (LMW) surfactants are used in the food industry as emulsifying (and foaming) ingredients and as stabilizers. These attributes are related to their ability to adsorb at fluid-fluid (and gas-fluid) interfaces lowering the interfacial (and surface) tension of liquids. Hence, the study of the properties of adsorbed layers of these molecules can be expected to lead to a better understanding of their effect on food products. Direct proof of the validity of mesoscopic models of systems of proteins and LMW surfactants can only be achieved by quantitative theoretical predictions being tested against both macroscopic and mesoscopic experiments. Computer simulation constitutes one of the few available tools to predict mathematically the behaviour of models of realistic complexity. Furthermore, experimental techniques such as atomic force microscopy (AFM) now allow high resolution imaging of these systems, providing the mesoscopic scale measurements to compare with the simulations. In this review, we bring together a number of related findings that have been generated at this mesoscopic level over the past few years. A useful simple model consisting of spherical particles interacting via bonded and unbonded forces is described, and the derived computer simulation results are compared against those from the imaging experiments. Special attention is paid to the adsorption of binary mixtures of proteins, mixtures of LMW surfactants, and also protein+surfactant mixed systems. We believe that further development of these mathematically well-defined physical models is necessary in order to achieve a proper understanding of the key physico-chemical processes involved.

We present Brownian dynamics simulations of the displacement of a protein monolayer by competitive adsorption. The protein film is modelled as a network of spherical bonded particles adsorbed at a fluid interface. Spherical displacer particles, which have a stronger affinity for the interface than the protein film particles, are introduced into the system through the sub-phase. At early stages, these particles diffuse to the interface and are adsorbed in the gaps in the network. Soon thereafter, however, further adsorption initiates displacement of the film particles, ultimately leading to the complete removal of the protein layer from the surface. We study the evolution of the number and size of the displacer islands formed at the interface. The introduction of a direct long-range repulsion between film and displacer particles is shown to lead to a phase-separation-type behaviour at intermediate time scales. Further comparisons with the displacement of a non-bonded monolayer are also presented.

The aim of this study was to characterize some phenotypic expressions of fibroblasts from the human oral mucosa. Gingival and lower forearm fibroblasts from young (20–30 years) and elderly (> 60 years) subjects, were analyzed. Gingival fibroblasts were taken from donors with (P) and without (NP) periodontal disease, while skin biopsies were taken from healthy subjects. Cell proliferation was assessed by evaluating the cell multiplication coefficient (C.M.C.). The proliferation potential of gingival fibroblasts from elderly individuals with and without periodontopathy did not differ from that of young subjects in the same condition but differed significantly in the skin samples. Enzyme neutral endopeptidase (EC 3.4.24.11) (NEP) activity, studied as a possible marker of cell ageing, showed an age-related increase in human skin fibroblasts but not consistently in gingival fibroblasts from individuals with or without periodontal disease. Cell area and substrate adhesion were evaluated by morphometric analysis. There were no significant differences between elderly P and NP subjects, while significant differences were observed between young and elderly P subjects. In conclusion, proliferative capacity and NEP activity in gingival fibroblasts did not appear to be age-related, probably because their microenvironment is continually moistened by saliva, which continues to contain growth factors, notably EGF, even into senescence. Tissue reaction and repair are important clinical and therapeutic implications.

A platelet (PLT) function modification has been reported in normal pregnancies compared with the nonpregnant condition and it has been hypothesized to play a central role in the pathogenesis of pregnancy-induced hypertension (PIH). The aims of the present study were (i) to evaluate the lipid composition, fluidity at different depths, transport functions, and ultrastructural features of the PLT membrane in PIH and (ii) to ascertain whether similar modifications may be determined by the state of pregnancy in comparison with the nonpregnant condition. The platelets of healthy pregnant women (HPW) showed: (i) an increase in Ca2+ ATPase activity, (ii) a decreased fluidity of the deeper site of the membrane, (iii) a reduced cholesterol concentration, with an increased ratio between unsaturated and saturated fatty acids; (iv) a decreased intramembranous particles (IMP) distribution factor (DF) of the plasma membrane E face in comparison with healthy nonpregnant women. When comparing women affected by PIH with HPW, we observed (i) reduced Na+/K+ ATPase activity and enhanced Ca2+ ATPase activity and intraplatelet calcium concentrations, (ii) an increased membrane fluidity, (iii) an increased cholesterol concentration and ratio between unsaturated and saturated fatty acids, (iv) a reduction of the IMP number and the DF. Pregnancy produces a deep modification of the platelet plasma membrane, and PIH produces a more pronounced alteration of the maternal platelets, which can be responsible for the observed modifications in placental blood flow and in the fetomaternal exchange.

A clinical-morphological study concerning tendon expansion has been carried out on a extensor tendon at the metacarpo-phalangeal joint presenting rigidity of the joint when extended. Surgical data showed that the tendon elongation after expander application was sufficient to allow its normal excursion up to the maximum flexion. Morphological analysis showed the presence in the expanded tendon areas of a high number of small diameter collagen fibrils. The capability of collagen fibrils to react against mechanical expansor stress, and reorganize a structural histoarchitecture of an immature type producing structural signs of normal behaviour has been tested.