Quantification of Mitral Regurgitation with Multiple Jets: In Vitro Comparison of Two-dimensional PISA techniques

Purpose: Traditionally, the proximal isovelocity surface area (PISA) is based on the assumption of a single hemisphere (hemispheric PISA), but this technique has not been validated for the quantification of mitral regurgitation (MR) with multiple jets. Methods: The left heart simulator was actuated by a pulsatile pump at various stroke amplitudes. The regurgitant volume (Rvol) passing through the mitral valve phantoms with single and double regurgitant orifices of varying size and interspace was quantified by a flowmeter as reference technique. Color Doppler 3-D full-volumes were obtained, and Rvol were derived from 2-D PISA surfaces on the basis of hemispheric and hemicylindric assumption with one base (partial hemicylindric PISA) or 2 bases (total hemicylindric PISA). Results: 72 regurgitant volumes (Rvol range: 8 to 76 ml/beat) were obtained. Hemispheric PISA Rvol correlated well with reference Rvol by one orifice (R²=0.97; bias -2.7±3.2ml), but less by ≥ one orifice (R²=0.89). When a fusion of two PISAs occured, addition of two hemispheric PISA overestimated Rvol (bias 9.1±12.2ml, fig.1), and single hemispheric PISA underestimated Rvol (bias -12.4±4.9ml). If an integrated approach was used (hemispheric in single orifice, total hemicylindric in two non-fused PISAs and partial hemicylindric in two fused PISAs), the correlation was R²=0.95, bias -1.6±5.6ml (fig.2). In the ROC analysis, the cutoff to detect ≥ moderate-to-severe Rvol (≥45ml) was 42ml (AUC 0.99, sens. 100%, spec. 93%). Conclusions: In MR with two regurgitant jets, the 2-D hemicylindric assumption of the PISA offers a better quantification of Rvol than the hemispheric assumption. Quantification of MR using 2-D PISA requires an integrated approach that considers number of regurgitant orifices and fusion of the PISAs.

Two-Dimensional Crystallisation of Membrane Proteins and Structural Assessment

Two-dimensional (2D) crystallisation of Membrane proteins reconstitutes them into their native environment, the lipid bilayer. Electron crystallography allows the structural analysis of these regular protein–lipid arrays up to atomic resolution. The crystal quality depends on the protein purity, ist stability and on the crystallisation conditions. The basics of 2D crystallisation and different recent advances are reviewed and electron crystallography approaches summarised. Progress in 2D crystallisation, sample preparation, image detectors and automation of the data acquisition and processing pipeline makes 2D electron crystallography particularly attractive for the structural analysis of membrane proteins that are too small for single-particle analyses and too unstable to form three-dimensional (3D) crystals.

Nonlinear dimension reduction in pathway-based genome-wide association analysis

Pathway based genome wide association study evolves from pathway analysis for microarray gene expression and is under rapid development as a complementary for single-SNP based genome wide association study. However, it faces new challenges, such as the summarization of SNP statistics to pathway statistics. The current study applies the ridge regularized Kernel Sliced Inverse Regression (KSIR) to achieve dimension reduction and compared this method to the other two widely used methods, the minimal-p-value (minP) approach of assigning the best test statistics of all SNPs in each pathway as the statistics of the pathway and the principal component analysis (PCA) method of utilizing PCA to calculate the principal components of each pathway. Comparison of the three methods using simulated datasets consisting of 500 cases, 500 controls and100 SNPs demonstrated that KSIR method outperformed the other two methods in terms of causal pathway ranking and the statistical power. PCA method showed similar performance as the minP method. KSIR method also showed a better performance over the other two methods in analyzing a real dataset, the WTCCC Ulcerative Colitis dataset consisting of 1762 cases, 3773 controls as the discovery cohort and 591 cases, 1639 controls as the replication cohort. Several immune and non-immune pathways relevant to ulcerative colitis were identified by these methods. Results from the current study provided a reference for further methodology development and identified novel pathways that may be of importance to the development of ulcerative colitis.^

Quantitative component analysis of the coarse fraction of surface sediments from the Persian Gulf

In the Persian Gulf and the Gulf of Oman marl forms the primary sediment cover, particularly on the Iranian side. A detailed quantitative description of the sediment components > 63 µ has been attempted in order to establish the regional distribution of the most important constituents as well as the criteria governing marl sedimentation in general. During the course of the analysis, the sand fraction from about 160 bottom-surface samples was split into 5 phi° fractions and 500 to 800 grains were counted in each individual fraction. The grains were cataloged in up to 40 grain type catagories. The gravel fraction was counted separately and the values calculated as weight percent. Basic for understanding the mode of formation of the marl sediment is the "rule" of independent availability of component groups. It states that the sedimentation of different component groups takes place independently, and that variation in the quantity of one component is independent of the presence or absence of other components. This means, for example, that different grain size spectrums are not necessarily developed through transport sorting. In the Persian Gulf they are more likely the result of differences in the amount of clay-rich fine sediment brought in to the restricted mouth areas of the Iranian rivers. These local increases in clayey sediment dilute the autochthonous, for the most part carbonate, coarse fraction. This also explains the frequent facies changes from carbonate to clayey marl. The main constituent groups of the coarse fraction are faecal pellets and lumps, the non carbonate mineral components, the Pleistocene relict sediment, the benthonic biogene components and the plankton. Faecal pellets and lumps are formed through grain size transformation of fine sediment. Higher percentages of these components can be correlated to large amounts of fine sediment and organic C. No discernable change takes place in carbonate minerals as a result of digestion and faecal pellet formation. The non-carbonate sand components originate from several unrelated sources and can be distinguished by their different grain size spectrum; as well as by other characteristics. The Iranian rivers supply the greatest amounts (well sorted fine sand). Their quantitative variations can be used to trace fine sediment transport directions. Similar mineral maxima in the sediment of the Gulf of Oman mark the path of the Persian Gulf outflow water. Far out from the coast, the basin bottoms in places contain abundant relict minerals (poorly sorted medium sand) and localized areas of reworked salt dome material (medium sand to gravel). Wind transport produces only a minimal "background value" of mineral components (very fine sand). Biogenic and non-biogenic relict sediments can be placed in separate component groups with the help of several petrographic criteria. Part of the relict sediment (well sorted fine sand) is allochthonous and was derived from the terrigenous sediment of river mouths. The main part (coarse, poorly sorted sediment), however, was derived from the late Pleistocene and forms a quasi-autochthonous cover over wide areas which receive little recent sedimentation. Bioturbation results in a mixing of the relict sediment with the overlying younger sediment. Resulting vertical sediment displacement of more than 2.5 m has been observed. This vertical mixing of relict sediment is also partially responsible for the present day grain size anomalies (coarse sediment in deep water) found in the Persian Gulf. The mainly aragonitic components forming the relict sediment show a finely subdivided facies pattern reflecting the paleogeography of carbonate tidal flats dating from the post Pleistocene transgression. Standstill periods are reflected at 110 -125m (shelf break), 64-61 m and 53-41 m (e.g. coare grained quartz and oolite concentrations), and at 25-30m. Comparing these depths to similar occurrences on other shelf regions (e. g. Timor Sea) leads to the conclusion that at this time minimal tectonic activity was taking place in the Persian Gulf. The Pleistocene climate, as evidenced by the absence of Iranian river sediment, was probably drier than the present day Persian Gulf climate. Foremost among the benthonic biogene components are the foraminifera and mollusks. When a ratio is set up between the two, it can be seen that each group is very sensitive to bottom type, i.e., the production of benthonic mollusca increases when a stable (hard) bottom is present whereas the foraminifera favour a soft bottom. In this way, regardless of the grain size, areas with high and low rates of recent sedimentation can be sharply defined. The almost complete absence of mollusks in water deeper than 200 to 300 m gives a rough sedimentologic water depth indicator. The sum of the benthonic foraminifera and mollusca was used as a relative constant reference value for the investigation of many other sediment components. The ratio between arenaceous foraminifera and those with carbonate shells shows a direct relationship to the amount of coarse grained material in the sediment as the frequence of arenaceous foraminifera depends heavily on the availability of sand grains. The nearness of "open" coasts (Iranian river mouths) is directly reflected in the high percentage of plant remains, and indirectly by the increased numbers of ostracods and vertebrates. Plant fragments do not reach their ultimate point of deposition in a free swimming state, but are transported along with the remainder of the terrigenous fine sediment. The echinoderms (mainly echinoids in the West Basin and ophiuroids in the Central Basin) attain their maximum development at the greatest depth reached by the action of the largest waves. This depth varies, depending on the exposure of the slope to the waves, between 12 to 14 and 30 to 35 m. Corals and bryozoans have proved to be good indicators of stable unchanging bottom conditions. Although bryozoans and alcyonarian spiculae are independent of water depth, scleractinians thrive only above 25 to 30 m. The beginning of recent reef growth (restricted by low winter temperatures) was seen only in one single area - on a shoal under 16 m of water. The coarse plankton fraction was studied primarily through the use of a plankton-benthos ratio. The increase in planktonic foraminifera with increasing water depth is here heavily masked by the "Adjacent sea effect" of the Persian Gulf: for the most part the foraminifera have drifted in from the Gulf of Oman. In contrast, the planktonic mollusks are able to colonize the entire Persian Gulf water body. Their amount in the plankton-benthos ratio always increases with water depth and thereby gives a reliable picture of local water depth variations. This holds true to a depth of around 400 m (corresponding to 80-90 % plankton). This water depth effect can be removed by graphical analysis, allowing the percentage of planktonic mollusks per total sample to be used as a reference base for relative sedimentation rate (sedimentation index). These values vary between 1 and > 1000 and thereby agree well with all the other lines of evidence. The "pteropod ooze" facies is then markedly dependent on the sedimentation rate and can theoretically develop at any depth greater than 65 m (proven at 80 m). It should certainly no longer be thought of as "deep sea" sediment. Based on the component distribution diagrams, grain size and carbonate content, the sediments of the Persian Gulf and the Gulf of Oman can be grouped into 5 provisional facies divisions (Chapt.19). Particularly noteworthy among these are first, the fine grained clayey marl facies occupying the 9 narrow outflow areas of rivers, and second, the coarse grained, high-carbonate marl facies rich in relict sediment which covers wide sediment-poor areas of the basin bottoms. Sediment transport is for the most part restricted to grain sizes < 150 µ and in shallow water is largely coast-parallel due to wave action at times supplemented by tidal currents. Below the wave base gravity transport prevails. The only current capable of moving sediment is the Persian Gulf outflow water in the Gulf of Oman.

Paleomagnetic analysed of two sediment cores off Cape Ghir

Holocene records documenting variations in direction and intensity of the geomagnetic field during the last about seven and a half millennia are presented for Northwest Africa. High resolution paleomagnetic analyses of two marine sediment sequences recovered from around 900 meter water depth on the upper continental slope off Cape Ghir (30°51'N, 10°16'W) were supplemented by magnetic measurements characterizing composition, concentration, grain size and coercivity of the magnetic mineral assemblage. Age control for the high sedimentation rate deposits (~60 cm/kyr) was established by AMS radiocarbon dates. The natural remanent magnetization (NRM) is very predominantly carried by a fine grained, mostly single domain (titano-)magnetite fraction allowing the reliable definition of stable NRM inclinations and declinations from alternating field demagnetization and principal component analysis. Predictions of the Korte and Constable (2005) geomagnetic field model CALS7K.2 for the study area are in fair agreement with the Holocene directional records for the most parts, yet noticeable differences exist in some intervals. The magnetic mineral inventory of the sediments reveals various climate controlled variations, specifically in concentration and grain size. A very strong impact had the mid-Holocene environmental change from humid to arid conditions on the African continent which also clearly affects relative paleointensity (RPI) estimates based on different remanence normalizers. To overcome this problem the pseudo-Thellier RPI technique has been applied. The results represent the first Holocene record of Earth's magnetic field intensity variations in the NW Africa region. It displays long term trends similar to those of model predictions, but also conspicuous millennium scale differences.

Climate change technology transfer to developing countries: evidence analysis and policy recommendations

Developing countries are experiencing unprecedented levels of economic growth. As a result, they will be responsible for most of the future growth in energy demand and greenhouse gas (GHG) emissions. Curbing GHG emissions in developing countries has become one of the cornerstones of a future international agreement under the United Nations Framework Convention for Climate Change (UNFCCC). However, setting caps for developing countries’ GHG emissions has encountered strong resistance in the current round of negotiations. Continued economic growth that allows poverty eradication is still the main priority for most developing countries, and caps are perceived as a constraint to future growth prospects. The development, transfer and use of low-carbon technologies have more positive connotations, and are seen as the potential path towards low-carbon development. So far, the success of the UNFCCC process in improving the levels of technology transfer (TT) to developing countries has been limited. This thesis analyses the causes for such limited success and seeks to improve on the understanding about what constitutes TT in the field of climate change, establish the factors that enable them in developing countries and determine which policies could be implemented to reinforce these factors. Despite the wide recognition of the importance of technology and knowledge transfer to developing countries in the climate change mitigation policy agenda, this issue has not received sufficient attention in academic research. Current definitions of climate change TT barely take into account the perspective of actors involved in actual climate change TT activities, while respective measurements do not bear in mind the diversity of channels through which these happen and the outputs and effects that they convey. Furthermore, the enabling factors for TT in non-BRIC (Brazil, Russia, India, China) developing countries have been seldom investigated, and policy recommendations to improve the level and quality of TTs to developing countries have not been adapted to the specific needs of highly heterogeneous countries, commonly denominated as “developing countries”. This thesis contributes to enriching the climate change TT debate from the perspective of a smaller emerging economy (Chile) and by undertaking a quantitative analysis of enabling factors for TT in a large sample of developing countries. Two methodological approaches are used to study climate change TT: comparative case study analysis and quantitative analysis. Comparative case studies analyse TT processes in ten cases based in Chile, all of which share the same economic, technological and policy frameworks, thus enabling us to draw conclusions on the enabling factors and obstacles operating in TT processes. The quantitative analysis uses three methodologies – principal component analysis, multiple regression analysis and cluster analysis – to assess the performance of developing countries in a number of enabling factors and the relationship between these factors and indicators of TT, as well as to create groups of developing countries with similar performances. The findings of this thesis are structured to provide responses to four main research questions: What constitutes technology transfer and how does it happen? Is it possible to measure technology transfer, and what are the main challenges in doing so? Which factors enable climate change technology transfer to developing countries? And how do different developing countries perform in these enabling factors, and how can differentiated policy priorities be defined accordingly? vi Resumen Los paises en desarrollo estan experimentando niveles de crecimiento economico sin precedentes. Como consecuencia, se espera que sean responsables de la mayor parte del futuro crecimiento global en demanda energetica y emisiones de Gases de Efecto de Invernadero (GEI). Reducir las emisiones de GEI en los paises en desarrollo es por tanto uno de los pilares de un futuro acuerdo internacional en el marco de la Convencion Marco de las Naciones Unidas para el Cambio Climatico (UNFCCC). La posibilidad de compromisos vinculantes de reduccion de emisiones de GEI ha sido rechazada por los paises en desarrollo, que perciben estos limites como frenos a su desarrollo economico y a su prioridad principal de erradicacion de la pobreza. El desarrollo, transferencia y uso de tecnologias bajas en carbono tiene connotaciones mas positivas y se percibe como la via hacia un crecimiento bajo en carbono. Hasta el momento, la UNFCCC ha tenido un exito limitado en la promocion de transferencias de tecnologia (TT) a paises en desarrollo. Esta tesis analiza las causas de este resultado y busca mejorar la comprension sobre que constituye transferencia de tecnologia en el area de cambio climatico, cuales son los factores que la facilitan en paises en desarrollo y que politicas podrian implementarse para reforzar dichos factores. A pesar del extendido reconocimiento sobre la importancia de la transferencia de tecnologia a paises en desarrollo en la agenda politica de cambio climatico, esta cuestion no ha sido suficientemente atendida por la investigacion existente. Las definiciones actuales de transferencia de tecnologia relacionada con la mitigacion del cambio climatico no tienen en cuenta la diversidad de canales por las que se manifiestan o los efectos que consiguen. Los factores facilitadores de TT en paises en desarrollo no BRIC (Brasil, Rusia, India y China) apenas han sido investigados, y las recomendaciones politicas para aumentar el nivel y la calidad de la TT no se han adaptado a las necesidades especificas de paises muy heterogeneos aglutinados bajo el denominado grupo de "paises en desarrollo". Esta tesis contribuye a enriquecer el debate sobre la TT de cambio climatico con la perspectiva de una economia emergente de pequeno tamano (Chile) y el analisis cuantitativo de factores que facilitan la TT en una amplia muestra de paises en desarrollo. Se utilizan dos metodologias para el estudio de la TT a paises en desarrollo: analisis comparativo de casos de estudio y analisis cuantitativo basado en metodos multivariantes. Los casos de estudio analizan procesos de TT en diez casos basados en Chile, para derivar conclusiones sobre los factores que facilitan u obstaculizan el proceso de transferencia. El analisis cuantitativo multivariante utiliza tres metodologias: regresion multiple, analisis de componentes principales y analisis cluster. Con dichas metodologias se busca analizar el posicionamiento de diversos paises en cuanto a factores que facilitan la TT; las relaciones entre dichos factores e indicadores de transferencia tecnologica; y crear grupos de paises con caracteristicas similares que podrian beneficiarse de politicas similares para la promocion de la transferencia de tecnologia. Los resultados de la tesis se estructuran en torno a cuatro preguntas de investigacion: .Que es la transferencia de tecnologia y como ocurre?; .Es posible medir la transferencia de tecnologias de bajo carbono?; .Que factores facilitan la transferencia de tecnologias de bajo carbono a paises en desarrollo? y .Como se puede agrupar a los paises en desarrollo en funcion de sus necesidades politicas para la promocion de la transferencia de tecnologias de bajo carbono?

Automatic motion compensation of free breathing acquired myocardial perfusion data by using independent component analysis

Images acquired during free breathing using first-pass gadolinium-enhanced myocardial perfusion magnetic resonance imaging (MRI) exhibit a quasiperiodic motion pattern that needs to be compensated for if a further automatic analysis of the perfusion is to be executed. In this work, we present a method to compensate this movement by combining independent component analysis (ICA) and image registration: First, we use ICA and a time?frequency analysis to identify the motion and separate it from the intensity change induced by the contrast agent. Then, synthetic reference images are created by recombining all the independent components but the one related to the motion. Therefore, the resulting image series does not exhibit motion and its images have intensities similar to those of their original counterparts. Motion compensation is then achieved by using a multi-pass image registration procedure. We tested our method on 39 image series acquired from 13 patients, covering the basal, mid and apical areas of the left heart ventricle and consisting of 58 perfusion images each. We validated our method by comparing manually tracked intensity profiles of the myocardial sections to automatically generated ones before and after registration of 13 patient data sets (39 distinct slices). We compared linear, non-linear, and combined ICA based registration approaches and previously published motion compensation schemes. Considering run-time and accuracy, a two-step ICA based motion compensation scheme that first optimizes a translation and then for non-linear transformation performed best and achieves registration of the whole series in 32 ± 12 s on a recent workstation. The proposed scheme improves the Pearsons correlation coefficient between manually and automatically obtained time?intensity curves from .84 ± .19 before registration to .96 ± .06 after registration

Membrane-bound state of the colicin E1 channel domain as an extended two-dimensional helical array

Atomic level structures have been determined for the soluble forms of several colicins and toxins, but the structural changes that occur after membrane binding have not been well characterized. Changes occurring in the transition from the soluble to membrane-bound state of the C-terminal 190-residue channel polypeptide of colicin E1 (P190) bound to anionic membranes are described. In the membrane-bound state, the α-helical content increases from 60–64% to 80–90%, with a concomitant increase in the average length of the helical segments from 12 to 16 or 17 residues, close to the length required to span the membrane bilayer in the open channel state. The average distance between helical segments is increased and interhelix interactions are weakened, as shown by a major loss of tertiary structure interactions, decreased efficiency of fluorescence resonance energy transfer from an energy donor on helix V of P190 to an acceptor on helix IX, and decreased resonance energy transfer at higher temperatures, not observed in soluble P190, implying freedom of motion of helical segments. Weaker interactions are also shown by a calorimetric thermal transition of low cooperativity, and the extended nature of the helical array is shown by a 3- to 4-fold increase in the average area subtended per molecule to 4,200 Å2 on the membrane surface. The latter, with analysis of the heat capacity changes, implies the absence of a developed hydrophobic core in the membrane-bound P190. The membrane interfacial layer thus serves to promote formation of a highly helical extended two-dimensional flexible net. The properties of the membrane-bound state of the colicin channel domain (i.e., hydrophobic anchor, lengthened and loosely coupled α-helices, and close association with the membrane interfacial layer) are plausible structural features for the state that is a prerequisite for voltage gating, formation of transmembrane helices, and channel opening.

Two-dimensional freezing in the liquid–vapor interface of a dilute Pb:Ga alloy

We report the results of x-ray reflectivity and grazing incidence x-ray diffraction studies of the liquid–vapor interface of a dilute alloy of Pb in Ga over the temperature range of 23–76°C. Our data show that the liquid–vapor interface of this alloy is stratified for several atomic diameters into the bulk liquid and that a monolayer of Pb forms the outermost stratum of the interface. Over the temperature range of 23–56°C, the monolayer of Pb is in an ordered hexagonal phase. At about 58°C, this monolayer undergoes a first-order transition to a hexatic phase, which remains stable to 76°C. An analogy between the observed transition and the first-order melting transition in a one-component classical plasma is suggested.