Three-dimensional structure of the flow inside the left ventricle of the human heart

The laboratory models of the human heart left ventricle developed in the last decades gave a valuable contribution to the comprehension of the role of the fluid dynamics in the cardiac function and to support the interpretation of the data obtained in vivo. Nevertheless, some questions are still open and new ones stem from the continuous improvements in the diagnostic imaging techniques. Many of these unresolved issues are related to the three-dimensional structure of the left-ventricular flow during the cardiac cycle. In this paper we investigated in detail this aspect using a laboratory model. The ventricle was simulated by a flexible sack varying its volume in time according to a physiologically shaped law. Velocities measured during several cycles on series of parallel planes, taken from two orthogonal points of view, were combined together in order to reconstruct the phase averaged, three-dimensional velocity field. During the diastole, three main steps are recognized in the evolution of the vortical structures: i) straight propagation in the direction of the long axis of a vortex-ring originated from the mitral orifice; ii) asymmetric development of the vortex-ring on an inclined plane; iii) single vortex formation. The analysis of three-dimensional data gives the experimental evidence of the reorganization of the flow in a single vortex persisting until the end of the diastole. This flow pattern seems to optimize the cardiac function since it directs velocity towards the aortic valve just before the systole and minimizes the fraction of blood residing within the ventricle for more cycles

Turbulence investigation in a laboratory model of the ascending aorta

This study aims to investigate turbulence inside a model of the human ascending aorta as a function of the main flow control parameters. For this purpose, we performed a two-dimensional in vitro investigation of the pulsatile flow inside a laboratory model of a healthy aorta by varying both the Reynolds and Womersley numbers. Our findings indicate that the velocity fluctuations become significant particularly during the deceleration phase of the flow, reach the maximum near the systolic peak and then decay during the rest of the diastole phase. Higher levels of turbulence were recovered for increasing Stroke Volumes, in particular maxima of Turbulent Kinetic Energy occurred in the bulk region while higher values of Reynolds shear stresses were found in correspondence of the sinus of Valsalva

CHALLENGING QUESTIONS IN CHEMISTRY: THE SYNERGIC ROLE OF AB-INITIO CALCULATIONS, X-RAY DERIVED CHARGE DENSITIES AND MODERN TOPOLOGICAL APPROACHES TO BONDING

This work deals with the role ab-initio calculations have in supporting and, when needed, helping to clarify the meaning of experimental findings. Furthermore, the extra information one gets from the wavefunction, that is the knowledge of the density matrix and of the pair density, both customarily unavailable from experiment, has revealed of uttermost importance in the study of the challenging chemical bond features investigated in this thesis. The charge densities of FeX2 marcasitic compounds, of crystalline K2SO4 and of a reference compound for magnetically active coordination polymers Zn(HCOO)2(H2O)2 have been analysed from both the experimental and crystallographic point of view

Interactions between permeation and gating in the TMEM16B/anoctamin2 calcium-activated chloride channel

At least two members of the TMEM16/anoctamin family, TMEM16A (also known as anoctamin1) and TMEM16B (also known as anoctamin2), encode Ca2+-activated Cl- channels (CaCCs), which are found in various cell types and mediate numerous physiological functions. Here, we used whole-cell and excised inside-out patch-clamp to investigate the relationship between anion permeation and gating, two processes typically viewed as independent, in TMEM16B expressed in HEK 293T cells. The permeability ratio sequence determined by substituting Cl- with other anions (PX/PCl) was SCN- > I- > NO3- > Br- > Cl- > F- > gluconate. When external Cl- was substituted with other anions, TMEM16B activation and deactivation kinetics at 0.5 μM Ca2+ were modified according to the sequence of permeability ratios, with anions more permeant than Cl- slowing both activation and deactivation and anions less permeant than Cl- accelerating them. Moreover, replacement of external Cl- with gluconate, or sucrose, shifted the voltage dependence of steady-state activation (G-V relation) to more positive potentials, whereas substitution of extracellular or intracellular Cl- with SCN- shifted G-V to more negative potentials. Dose-response relationships for Ca2+ in the presence of different extracellular anions indicated that the apparent affinity for Ca2+ at +100 mV increased with increasing permeability ratio. The apparent affinity for Ca2+ in the presence of intracellular SCN- also increased compared with that in Cl-. Our results provide the first evidence that TMEM16B gating is modulated by permeant anions and provide the basis for future studies aimed at identifying the molecular determinants of TMEM16B ion selectivity and gating. © 2014 Betto et al

Three-dimensional structure of the flow inside the left ventricle of the human heart

Exp Fluids (2013) 54(1):1-9 The final publication is available at Springer via http://dx.doi.org/10.1007/s00348-013-1609-0 1 The laboratory models of the human heart left ventricle developed in the last decades gave a valuable contribution to the comprehension of the role of the fluid dynamics in the cardiac function and to support the interpretation of the data obtained in vivo. Nevertheless, some questions are still open and new ones stem from the continuous improvements in the diagnostic imaging techniques. Many of these unresolved issues are related to the three-dimensional structure of the leftventricular flow during the cardiac cycle. In this paper we investigated in detail this aspect using a laboratory model. The ventricle was simulated by a flexible sack varying its volume in time according to a physiologically shaped law. Velocities measured during several cycles on series of parallel planes, taken from two orthogonal points of view, were combined together in order to reconstruct the phase averaged, threedimensional velocity field. During the diastole, three main steps are recognized in the evolution of the vortical structures: i) straight propagation in the direction of the long axis of a vortex-ring originated from the mitral orifice; ii) asymmetric development of the vortex-ring on an inclined plane; iii) single vortex formation. The analysis of three-dimensional data gives the experimental evidence of the reorganization of the flow in a single vortex persisting until the end of the diastole. This flow pattern seems to optimize the cardiac function since it directs velocity towards the aortic valve just before the systole and minimizes the fraction of blood residing within the ventricle for more cycles

Electronic structure and magnetic coupling of pure and Mg-doped KCuF3

We investigated the electronic and magnetic properties of KCuF3 and KCu0.875Mg0.125F3 crystals by means of Density Functional periodic computations at the B3LYP level of theory. We considered four possible magnetic ordering of the unpaired electrons on copper ions. Both materials are correctly predicted as being 1D antiferromagnetic insulators, and the superexchange parameters in the crystallographic ab planes and along the c direction measure +10 and-600 K, respectively. Residual spin polarization is found also on fluorine atoms, in agreement with literature results. We found a complete orbital ordering at Cu sites: In the copper reference frame dxy, dyz, dxz, and dz2 orbitals contain about 2 electrons each, while the dx2-y2 orbital is only partially filled. The perturbation induced by doping of KCuF3 with Mg is very strong and localized on the first shell of F neighbours. Mg has a very small influence on the ordering of the 3d orbitals of copper and on the Cu-Cu magnetic superexchange parameters but reduces significantly the absolute energy differences between the antiferromagnetic ground state and the ferromagnetic phase, in agreement with the experiment. The absence of long range effects makes Mg a suitable dopant for the investigation of strongly correlated electronic systems by means of orbital dilution

Efficacy of Conventional and Organic Insecticides against Scaphoideus titanus: Field and Semi-Field Trials

Scaphoideus titanus is the main vector of phytoplasmas associated with Flavescence dorée (FD), one of the most serious threats to viticulture in many European countries. To minimize the spread of this disease, mandatory control measures against S. titanus were decided in Europe. In the 1990s, the repeated application of insecticides (mainly organophosphates) proved to be an effective measure to control the vector and the related disease in north-eastern Italy. These insecticides and most of the neonicotinoids were recently banned from European viticulture. Serious FD issues detected in the recent years in northern Italy could be related to the use of less effective insecticides. Trials aimed at evaluating the efficacy of the most used conventional and organic insecticides in the control of S. titanus have been performed in semi-field and field conditions to test this hypothesis. In efficacy trials, carried out in four vineyards, etofenprox and deltamethrin proved to be the best conventional insecticides, while pyrethrins were the most impactful among organic insecticides. Insecticide residual activity was evaluated in semi-field and field conditions. Acrinathrin showed the most significant residual effects in both conditions. In semi-field trials, most of the pyrethroids were associated with good results in terms of residual activity. However, these effects declined in field conditions, probably due to high temperatures. Organic insecticides showed poor results in terms of residual efficacy. Implications of these results in the context of Integrated Pest Management in conventional and organic viticulture are discussed

Experimental study of Taylor's hypothesis in a turbulent soap film

An experimental study of Taylor's hypothesis in a quasi-two-dimensional turbulent soap film is presented. A two probe laser Doppler velocimeter enables a non-intrusive simultaneous measurement of the velocity at spatially separated points. The breakdown of Taylor's hypothesis is quantified using the cross correlation between two points displaced in both space and time; correlation is better than 90% for scales less than the integral scale. A quantitative study of the decorrelation beyond the integral scale is presented, including an analysis of the failure of Taylor's hypothesis using techniques from predictability studies of turbulent flows. Our results are compared with similar studies of 3D turbulence.Comment: 27 pages, + 19 figure

Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.

Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF). A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16) or anoctamin (ANO). TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT). The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability

Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment

Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3 h. Cell seeding and in vivo experiments are necessary to proceed towards clinical translation