Relationship between haemodynamics and morphology in pulmonary hypertension. A quantitative intravascular ultrasound study

BACKGROUND: Intravascular ultrasound imaging of the pulmonary arteries has been demonstrated to be a reliable method of quantifying vessel diameter, luminal area and pulsatility. Simultaneous measurement of flow velocity and its response to vasodilators allows the relationship between morphology and functional compromise to be studied, especially endothelial dysfunction. METHODS: In 51 patients (mean age = 49.8 +/- 12.6 years, 17 female) we performed right heart catheterization and simultaneous intravascular ultrasound of pulmonary artery branches. The patients were divided in two groups: group 1 with normal pulmonary artery pressure and pulmonary vascular resistance, and group 2 with pulmonary hypertension (peak pulmonary artery pressure > 30 mmHg and/or mean pulmonary artery pressure > 20 mmHg). Vessel wall and lumen were studied using a 2.9 F intravascular ultrasound catheter with a 30 MHz phased array transducer. Measurement of blood flow velocity was accomplished by a Doppler flow wire (0.018 inch). The maximal flow change during acetylcholine infusion (adjusted to 10(-6); 10(-5), and 10(-4) M concentration in the blood vessel) was measured. RESULTS: There were no significant differences between groups 1 and 2 with respect to age (48.5 +/- 14.3 years vs 50.3 +/- 12.3 years; P = ns), gender (4 female/8 male vs 13 female/26 male; P = ns), luminal area of the vessel segment in which the intravascular ultrasound measurements were obtained (11.8 +/- 6.1 mm2 vs 16.7 +/- 14.3 mm2; P = ns), internal diameter (3.9 +/- 1.2 mm vs 4.2 +/- 1.7 mm; P = ns), and external diameter (6.1 +/- 1.3 mm vs 6.9 +/- 2.1 mm; P = ns). Cross-sectional images of the pulmonary artery wall demonstrated a single ring with high echodensity with a thin inner layer regarded as intima in group 1. In contrast, the majority of patients (n = 35/39) in group 2 demonstrated a thickening of the intimal layer and/or a disturbance of layering of the echogenic arterial wall. The relative wall thickness was higher in group 2 than in group 1 (22.5 +/- 10.4% vs 15.3 +/- 6.5%; P < 0.05). There were no significant correlations between pulmonary artery pressure and wall thickness pulmonary artery pressure and area change in the cardiac cycle, acetylcholine-dependent increase in pulmonary flow and morphological changes in the vessel wall. CONCLUSION: We conclude that intravascular ultrasound is capable of detecting morphological changes in the pulmonary vessel wall in pulmonary hypertension and that vessel wall hypertrophy of small pulmonary segment arteries, as detected by intravascular ultrasound, is not predictive of functional vasodilatory response of resistance vessels of the same vessel area.     

The microscopy cell (MicCell), a versatile modular flowthrough system for cell biology, biomaterial research, and nanotechnology

We describe a novel microfluidic perfusion system for high-resolution microscopes. Its modular design allows pre-coating of the coverslip surface with reagents, biomolecules, or cells. A poly(dimethylsiloxane) (PDMS) layer is cast in a special molding station, using masters made by photolithography and dry etching of silicon or by photoresist patterning on glass or silicon. This channel system can be reused while the coverslip is exchanged between experiments. As normal fluidic connectors are used, the link to external, computer-programmable syringe pumps is standardized and various fluidic channel networks can be used in the same setup. The system can house hydrogel microvalves and microelectrodes close to the imaging area to control the influx of reaction partners. We present a range of applications, including single-molecule analysis by fluorescence correlation spectroscopy (FCS), manipulation of single molecules for nanostructuring by hydrodynamic flow fields or the action of motor proteins, generation of concentration gradients, trapping and stretching of live cells using optical fibers precisely mounted in the PDMS layer, and the integration of microelectrodes for actuation and sensing.     

Chemical warfare and survival strategies in bacterial range expansions

Dispersal of species is a fundamental ecological process in the evolution and maintenance of biodiversity. Limited control over ecological parameters has hindered progress in understanding of what enables species to colonize new areas, as well as the importance of interspecies interactions. Such control is necessary to construct reliable mathematical models of ecosystems. In our work, we studied dispersal in the context of bacterial range expansions and identified the major determinants of species coexistence for a bacterial model system of three Escherichia coli strains (toxin-producing, sensitive and resistant). Genetic engineering allowed us to tune strain growth rates and to design different ecological scenarios (cyclic and hierarchical). We found that coexistence of all strains depended on three strongly interdependent factors: composition of inoculum, relative strain growth rates and effective toxin range. Robust agreement between our experiments and a thoroughly calibrated computational model enabled us to extrapolate these intricate interdependencies in terms of phenomenological biodiversity laws. Our mathematical analysis also suggested that cyclic dominance between strains is not a prerequisite for coexistence in competitive range expansions. Instead, robust three-strain coexistence required a balance between growth rates and either a reduced initial ratio of the toxin-producing strain, or a sufficiently short toxin range.     

Mixed crystalline films of co-evaporated hydrogen- and fluorine-terminated phthalocyanines and their application in photovoltaic devices

Blends of organic electron and hole conductive materials are widely used for ambipolar charge carrier transport and photovoltaic cells. An obvious choice for donor–acceptor blends are organic semiconducting materials in their hydrogenated and fluorinated form, since they combine potentially suitable electronic properties with structural compatibility of the two constituents. This study focuses on the structural, optical, and electrical properties of blends using hydrogenated copper-phthalocyanine (H₁₆CuPc) in combination with its per-fluorinated version (F₁₆CuPc). Using X-ray scattering, scanning force microscopy and optical absorption measurements we show that mixed crystalline films are obtained by co-evaporation of the two materials. Electrical transport measurements reveal a profound reduction of the current for bipolar charge injection in mixed films. We discuss the formation of self-trapped charge transfer excitons as possible explanation for this unexpected behaviour, which impedes the usability of this system in photovoltaic cells.     

Interaction of hIAPP with Model Raft Membranes and Pancreatic β‐Cells: Cytotoxicity of hIAPP Oligomers

Type II diabetes mellitus (T2DM) is associated with β‐cell failure, which correlates with the formation of pancreatic islet amyloid deposits. The human islet amyloid polypeptide (hIAPP) is the major component of islet amyloid and undergoes structural changes followed by self‐association and pathological tissue deposition during aggregation in T2DM. There is clear evidence that the aggregation process is accelerated in the presence of particular lipid membranes. Whereas hIAPP aggregation has been extensively studied in homogeneous model membrane systems, especially negatively charged lipid bilayers, information on the interaction of hIAPP with heterogeneous model raft membranes has been missing until now. In the present study, we focus on the principles of aggregation and amyloid formation of hIAPP in the presence of model raft membranes. Time‐lapse tapping mode AFM and confocal fluorescence microscopy experiments followed membrane permeabilization and localization of hIAPP in the raft membrane. Together with the ThT and WST‐1 assay, the data revealed elevated cytotoxicity of hIAPP oligomers on INS‐1E cells.     

Binding of 2-azaanthraquinone derivatives to DNA and their interference with the activity of DNA topoisomerases in vitro

We have investigated the binding ability to DNA of compounds belonging to the 2-azaanthraquinone-type structure and have examined the effect on the activity of DNA gyrase as well as on mammalian topoisomerases in vitro. Using different biophysical techniques it was found that one of these ligands, 9-((2-dimethylamino)ethyl)amino)-6-hydroxy-7-methoxy-5, 10-dihydroxybenzo[g]isoquinoline-5,10-dione (TPL-I), is an intercalating DNA binding agent, whereas the parent compound tolypocladin (TPL) and a derivative (TPL-II) showed almost no similar affinity to DNA. CD measurements demonstrated a significant and selective binding tendency of TPL-I to alternating purine/pyrimidine sequences with some preference for poly(dA-dT). poly(dA-dT). Tm values were increased of the ligand complex with the alternating AT-containing duplex polymer. The binding to various DNAs was characterized by CD and visible absorption spectral changes. From the latter, different binding constants of 6.2 x 10(5) and 1.5 x 10(5) M-1 were obtained for poly(dA-dT).poly(dA-dT) and poly(dA). poly(dT), respectively. Sedimentation measurements with supercoiled pBR322 plasmid DNA clearly indicated an intercalative binding mechanism associated with an unwinding angle of about 18 degrees. These results suggest that the intercalative binding of TPL-I is promoted by the 2-(dimethylamino)ethylamino group substituted on carbon 9 of the anthraquinone system. The cytotoxic compound TPL-I, but not TPL or TPL-II, effectively inhibited the DNA supercoiling reaction of DNA gyrase and the activity of mammalian topoisomerases I and II as measured by the relaxation assay. TPL-I affects the cleavage reaction of topoisomerases on a single site located in alternating purine-pyrimidine sequence regions. The inhibitory potency of TPL-I can be ascribed to a blocking of cleavage sites on the DNA substrate, which correlates with the sequence preference of the ligand.     

Determination of factors relating to materials calculation in the limit state method for its application to plastic material-structures

A realistic calculation and dimensioning of plastic material structures has to consider the variations of the actions upon the structure as well as the behaviour variations of the plastic materials used. The calculation method based on the limiting states presupposes the determination of standard values as well as uniformity and adaptation factors for the plastic materials. The relevant research problems are described.