Relationship between microalbuminuria and cardiac structural changes in mild hypertensive patients

The aim of this study was to determine the relationship between urinary albumin excretion (UAE), cardiac structural changes upon echocardiography and 24-h ambulatory blood pressure (ABPM) levels. Twenty mild hypertensive patients (mean age 56.8 ± 9.6 years) were evaluated. After 2 weeks of a washout period of all antihypertensive drugs, all patients underwent an echocardiographic evaluation, a 24-h ABPM and an overnight urine collection. Systolic and diastolic blood pressure during 24-h ABPM was 145 ± 14/91 ± 10 mmHg (daytime) and 130 ± 14/76 ± 8 mmHg (nighttime), respectively. Seven (35%) patients presented UAE > or = 15 µg/min, and for the whole group, the geometric mean value for UAE was 10.2 x/÷ 3.86 µg/min. Cardiac measurements showed mean values of interventricular septum thickness (IVS) of 11 ± 2.3 mm, left ventricular posterior wall thickness (PWT) of 10 ± 2.0 mm, left ventricular mass (LVM) of 165 ± 52 g, and left ventricular mass index (LVMI) of 99 ± 31 g/m². A forward stepwise regression model indicated that blood pressure levels did not influence UAE. Significant correlations were observed between UAE and cardiac structural parameters such as IVS (r = 0.71, P<0.001), PWT (r = 0.64, P<0.005), LVM (r = 0.65, P<0.005) and LVMI (r = 0.57, P<0.01). Compared with normoalbuminuric patients, those who had microalbuminuria presented higher values of all cardiac parameters measured. The predictive positive and negative values of UAE > or = 15 µg/min for the presence of geometric cardiac abnormalities were 75 and 91.6%. These data indicate that microalbuminuria in essential hypertension represents an early marker of cardiac structural damage.

The use and misuse of the "impact factor" as a parameter for evaluation of scientific publication quality: a proposal to rationalize its application

We present a critical analysis of the generalized use of the "impact factor". By means of the Kruskal-Wallis test, it was shown that it is not possible to compare distinct disciplines using the impact factor without adjustments. After assigning the median journal the value of one (1.000), the impact factor value for each journal was calculated by the rule of three. The adjusted values were homogeneous, thus permitting comparison among distinct disciplines.

Genesis and Evolution of Brittle Structures In Southwestern Finland and Western South Africa. Insights into Fault Reactivation, Fluid Flow and Structural Maturity in Precambrian Cratons

The bedrock of old crystalline cratons is characteristically saturated with brittle structures formed during successive superimposed episodes of deformation and under varying stress regimes. As a result, the crust effectively deforms through the reactivation of pre-existing structures rather than by through the activation, or generation, of new ones, and is said to be in a state of 'structural maturity'. By combining data from Olkiluoto Island, southwestern Finland, which has been investigated as the potential site of a deep geological repository for high-level nuclear waste, with observations from southern Sweden, it can be concluded that the southern part of the Svecofennian shield had already attained structural maturity during the Mesoproterozoic era. This indicates that the phase of activation of the crust, i.e. the time interval during which new fractures were generated, was brief in comparison to the subsequent reactivation phase. Structural maturity of the bedrock was also attained relatively rapidly in Namaqualand, western South Africa, after the formation of first brittle structures during Neoproterozoic time. Subsequent brittle deformation in Namaqualand was controlled by the reactivation of pre-existing strike-slip faults.In such settings, seismic events are likely to occur through reactivation of pre-existing zones that are favourably oriented with respect to prevailing stresses. In Namaqualand, this is shown for present day seismicity by slip tendency analysis, and at Olkiluoto, for a Neoproterozoic earthquake reactivating a Mesoproterozoic fault. By combining detailed field observations with the results of paleostress inversions and relative and absolute time constraints, seven distinctm superimposed paleostress regimes have been recognized in the Olkiluoto region. From oldest to youngest these are: (1) NW-SE to NNW-SSE transpression, which prevailed soon after 1.75 Ga, when the crust had sufficiently cooled down to allow brittle deformation to occur. During this phase conjugate NNW-SSE and NE-SW striking strike-slip faults were active simultaneous with reactivation of SE-dipping low-angle shear zones and foliation planes. This was followed by (2) N-S to NE-SW transpression, which caused partial reactivation of structures formed in the first event; (3) NW-SE extension during the Gothian orogeny and at the time of rapakivi magmatism and intrusion of diabase dikes; (4) NE-SW transtension that occurred between 1.60 and 1.30 Ga and which also formed the NW-SE-trending Satakunta graben located some 20 km north of Olkiluoto. Greisen-type veins also formed during this phase. (5) NE-SW compression that postdates both the formation of the 1.56 Ga rapakivi granites and 1.27 Ga olivine diabases of the region; (6) E-W transpression during the early stages of the Mesoproterozoic Sveconorwegian orogeny and which also predated (7) almost coaxial E-W extension attributed to the collapse of the Sveconorwegian orogeny. The kinematic analysis of fracture systems in crystalline bedrock also provides a robust framework for evaluating fluid-rock interaction in the brittle regime; this is essential in assessment of bedrock integrity for numerous geo-engineering applications, including groundwater management, transient or permanent CO2 storage and site investigations for permanent waste disposal. Investigations at Olkiluoto revealed that fluid flow along fractures is coupled with low normal tractions due to in-situ stresses and thus deviates from the generally accepted critically stressed fracture concept, where fluid flow is concentrated on fractures on the verge of failure. The difference is linked to the shallow conditions of Olkiluoto - due to the low differential stresses inherent at shallow depths, fracture activation and fluid flow is controlled by dilation due to low normal tractions. At deeper settings, however, fluid flow is controlled by fracture criticality caused by large differential stress, which drives shear deformation instead of dilation.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Specific structural features of syndecans and heparan sulfate chains are needed for cell signaling

The syndecans, heparan sulfate proteoglycans, are abundant molecules associated with the cell surface and extracellular matrix and consist of a protein core to which heparan sulfate chains are covalently attached. Each of the syndecan core proteins has a short cytoplasmic domain that binds cytosolic regulatory factors. The syndecans also contain highly conserved transmembrane domains and extracellular domains for which important activities are becoming known. These protein domains locate the syndecan on cell surface sites during development and tumor formation where they interact with other receptors to regulate signaling and cytoskeletal organization. The functions of cell surface heparan sulfate proteoglycan have been centered on the role of heparan sulfate chains, located on the outer side of the cell surface, in the binding of a wide array of ligands, including extracellular matrix proteins and soluble growth factors. More recently, the core proteins of the syndecan family transmembrane proteoglycans have also been shown to be involved in cell signaling through interaction with integrins and tyrosine kinase receptors.

Parameter identification in time series models

Time series analysis can be categorized into three different approaches: classical, Box-Jenkins, and State space. Classical approach makes a basement for the analysis and Box-Jenkins approach is an improvement of the classical approach and deals with stationary time series. State space approach allows time variant factors and covers up a broader area of time series analysis. This thesis focuses on parameter identifiablity of different parameter estimation methods such as LSQ, Yule-Walker, MLE which are used in the above time series analysis approaches. Also the Kalman filter method and smoothing techniques are integrated with the state space approach and MLE method to estimate parameters allowing them to change over time. Parameter estimation is carried out by repeating estimation and integrating with MCMC and inspect how well different estimation methods can identify the optimal model parameters. Identification is performed in probabilistic and general senses and compare the results in order to study and represent identifiability more informative way.

Intensification of hemicellulose hot-water extraction from spruce wood by parameter tuning

The growing population on earth along with diminishing fossil deposits and the climate change debate calls out for a better utilization of renewable, bio-based materials. In a biorefinery perspective, the renewable biomass is converted into many different products such as fuels, chemicals, and materials, quite similar to the petroleum refinery industry. Since forests cover about one third of the land surface on earth, ligno-cellulosic biomass is the most abundant renewable resource available. The natural first step in a biorefinery is separation and isolation of the different compounds the biomass is comprised of. The major components in wood are cellulose, hemicellulose, and lignin, all of which can be made into various end-products. Today, focus normally lies on utilizing only one component, e.g., the cellulose in the Kraft pulping process. It would be highly desirable to utilize all the different compounds, both from an economical and environmental point of view. The separation process should therefore be optimized. Hemicelluloses can partly be extracted with hot-water prior to pulping. Depending in the severity of the extraction, the hemicelluloses are degraded to various degrees. In order to be able to choose from a variety of different end-products, the hemicelluloses should be as intact as possible after the extraction. The main focus of this work has been on preserving the hemicellulose molar mass throughout the extraction at a high yield by actively controlling the extraction pH at the high temperatures used. Since it has not been possible to measure pH during an extraction due to the high temperatures, the extraction pH has remained a “black box”. Therefore, a high-temperature in-line pH measuring system was developed, validated, and tested for hot-water wood extractions. One crucial step in the measurements is calibration, therefore extensive efforts was put on developing a reliable calibration procedure. Initial extractions with wood showed that the actual extraction pH was ~0.35 pH units higher than previously believed. The measuring system was also equipped with a controller connected to a pump. With this addition it was possible to control the extraction to any desired pH set point. When the pH dropped below the set point, the controller started pumping in alkali and by that the desired set point was maintained very accurately. Analyses of the extracted hemicelluloses showed that less hemicelluloses were extracted at higher pH but with a higher molar-mass. Monomer formation could, at a certain pH level, be completely inhibited. Increasing the temperature, but maintaining a specific pH set point, would speed up the extraction without degrading the molar-mass of the hemicelluloses and thereby intensifying the extraction. The diffusion of the dissolved hemicelluloses from the wood particle is a major part of the extraction process. Therefore, a particle size study ranging from 0.5 mm wood particles to industrial size wood chips was conducted to investigate the internal mass transfer of the hemicelluloses. Unsurprisingly, it showed that hemicelluloses were extracted faster from smaller wood particles than larger although it did not seem to have a substantial effect on the average molar mass of the extracted hemicelluloses. However, smaller particle sizes require more energy to manufacture and thus increases the economic cost. Since bark comprises 10 – 15 % of a tree, it is important to also consider it in a biorefinery concept. Spruce inner and outer bark was hot-water extracted separately to investigate the possibility to isolate the bark hemicelluloses. It was showed that the bark hemicelluloses comprised mostly of pectic material and differed considerably from the wood hemicelluloses. The bark hemicelluloses, or pectins, could be extracted at lower temperatures than the wood hemicelluloses. A chemical characterization, done separately on inner and outer bark, showed that inner bark contained over 10 % stilbene glucosides that could be extracted already at 100 °C with aqueous acetone.

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37) on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively). Three cells (4.5%) were bistratified, having thick dendrites, and the others (95.5%) were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40%) and 2 groups with inner (50-100%) stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

The effect of focal point parameters in fiber laser welding of structural steel

In this thesis the effect of focal point parameters in fiber laser welding of structural steel is studied. The goal is to establish relations between laser power, focal point diameter and focal point position with the resulting quality, weld-bead geometry and hardness of the welds. In the laboratory experiments, AB AH36 shipbuilding steel was welded in an I-butt joint configuration using IPG YLS-10000 continuous wave fiber laser. The quality of the welds produced were evaluated based on standard SFS-EN ISO 13919-1. The weld-bead geometry was defined from the weld cross-sections and Vickers hardness test was used to measure hardness's from the middle of the cross-sections. It was shown that all the studied focal point parameters have an effect on the quality, weld-bead geometry and hardness of the welds produced.

First-principles study on electronic and structural properties of Cu(In/Ga)Se alloys for solar cells

Thin-film photovoltaic solar cells based on the Cu(In1−xGax)Se2 (CIGS) alloys have attracted more and more attention due to their large optical absorption coefficient, long term stability, low cost, and high efficiency. Modern theoretical studies of this material with first-principles calculations can provide accurate description of the electronic structure and yield results in close agreement with experimental values, but takes a large amount of calculation time. In this work, we use first-principles calculations based on the computationally affordable meta- generalized gradient approximation of the density-functional theory to investigate electronic and structural properties of the CIGS alloys. We report on the simulation of the lattice parameters and band gaps, as a function of chemical composition. The obtained results were found to be in a good agreement with the available experimental data.

Structural and functional Studies of angucycline tailoring enzymes

Polyketides are a diverse group of natural products produced in many bacteria, fungi and plants. These metabolites have diverse biological activities and several members of this group are in clinical use as antibiotics, anticancer agents, antifungals and immunosuppressants. The different polyketides are produced by polyketide synthases, which catalyze the condensation of extender units into various polyketide scaffolds. After the biosynthesis of the polyketide backbone, more versatility is created to the molecule by tailoring enzymes catalyzing for instance hydroxylations, methylations and glycosylations. Flavoprotein monooxygenases (FPMO) and short-chain alcohol dehydrogenases/reductases (SDR) are two enzyme families that catalyze unusual tailoring reactions in the biosynthesis of natural products. In the experimental section, functions of homologous FPMO and SDR tailoring enzymes from five different angucycline pathways were studied in vitro. The results revealed how different angucyclinones are produced from a common intermediate and that FPMO JadH and SDR LanV are responsible for the divergence of jadomycins and landomycins, respectively, from other angucyclines. Structural studies of these tailoring enzymes revealed differences between homologous enzymes and enabled the use of structure-based protein engineering. Mutagenesis experiments gave important information about the enzymes behind the evolution of distinct angucycline metabolites. These experiments revealed a correlation between the substrate inhibition and bi-functionality in JadH homologue PgaE. In the case of LanV, analysis of mutagenesis results revealed that the difference between the stereospecificities of LanV and its homologues CabV and UrdMred is unexpectedly related to the conformation of the substrate rather than to the structure of the enzyme. Altogether, the results presented here have improved our knowledge about different steps of angucycline biosynthesis and the reaction mechanisms used by the tailoring enzymes behind these steps. This information can hopefully be used to modify these enzymes to produce novel metabolites, which have new biological targets or possess novel modes-of-action. The understanding of these unusual enzyme mechanisms is also interesting to enzymologists outside the field of natural product research.

Differences in functional and structural properties of segments of the rat tail artery

The investigation of resistance vessels is generally costly and difficult to execute. The present study investigated the diameters and the vascular reactivity of different segments of the rat tail artery (base, middle, and tail end) of 30 male Wister rats (EPM strain) to characterize a conductance or resistance vessel, using a low-cost simple technique. The diameters (mean ± SEM) of the base and middle segments were 471 ± 4.97 and 540 ± 8.39 µm, respectively, the tail end was 253 ± 2.58 µm. To test reactivity, the whole tail arteries or segments were perfused under constant flow and the reactivity to phenylephrine (PHE; 0.01-300 µg) was evaluated before and after removal of the endothelium or drug administration. The maximal response (Emax) and sensitivity (pED50) to PHE of the whole tail and the base segment increased after endothelium removal or treatment with 100 µM L-NAME, which suggests modulation by nitric oxide. Indomethacin (10 µM) and tetraethylammonium (5 mM) did not change the Emax or pED50 of these segments. PHE and L-NAME increased the pED50 of the middle and the tail end only and indomethacin did not change pED50 or Emax. Tetraethylammonium increased the sensitivity only at the tail end, which suggests a blockade of vasodilator release. Results indicate that the proximal segment of the tail artery possesses a diameter compatible with a conductance vessel, while the tail end has the diameter of a resistance vessel. In addition, the vascular reactivity to PHE in the proximal segment is nitric oxide-dependent, while the tail end is dependent on endothelium-derived hyperpolarizing factor.

Biomechanics and structural adaptations of the rat femur after hindlimb suspension and treadmill running

We microscopically and mechanically evaluated the femurs of rats subjected to hindlimb unloading (tail suspension) followed by treadmill training. Female Wistar rats were randomly divided into five groups containing 12-14 rats: control I (118 days old), control II (139 days old), suspended (tail suspension for 28 days), suspended-released (released for 21 days after 28 days of suspension), and suspended-trained (trained for 21 days after 28 days of suspension). We measured bone resistance by bending-compression mechanical tests of the entire proximal half of the femur and three-point bending tests of diaphyseal cortical bone. We determined bone microstructure by tetracycline labeling of trabecular and cortical bone. We found that tail suspension weakened bone (ultimate load = 86.3 ± 13.5 N, tenacity modulus = 0.027 ± 0.011 MPa·m vs ultimate load = 101.5 ± 10.5 N, tenacity modulus = 0.019 ± 0.006 MPa·m in control I animals). The tenacity modulus for suspended and released animals was 0.023 ± 0.010 MPa·m vs 0.046 ± 0.018 MPa·m for trained animals and 0.035 ± 0.010 MPa·m for control animals. These data indicate that normal activity and training resulted in recovered bone resistance, but suspended-released rats presented femoral head flattening and earlier closure of the growth plate. Microscopically, we found that suspension inhibited new bone subperiosteal and endosteal formation. The bone disuse atrophy secondary to hypoactivity in rats can be reversed by an early regime of exercising, which is more advantageous than ordinary cage activities alone.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.