1,636 research outputs found
Mesoscopic light transport by very strong collective multiple scattering in nanowire mats
Under the extreme condition of the scattering length being much shorter than the wavelength, light transport in random media is strongly modified by mesoscopic interference, and can even be halted in an effect known as Anderson localization. Anderson localization in three dimensions has recently been realized for acoustic waves and for cold atoms. Mats of disordered, high-refractive-index semiconductor nanowires are one of the strongest three-dimensional scattering materials for light, but localization has not been shown. Here, we use statistical methods originally developed for microwave waveguides to demonstrate that transport of light through nanowire mats is strongly correlated and governed by mesoscopic interference contributions. Our results confirm the contribution of only a few open modes to the transmission
Development policy in crisis: The case of Sub-Saharan africa and its consequences for cooperation
The present crisis symptoms evident in most developing economies are particularly pronounced in black Africa. Although this is largely due to factors beyond the control of the countries concerned, inappropriate development strategies have aggravated their effects. In order to mobilize the black African countries' own potential for development, a reorientation of both their internal policies and their cooperation with industrialised countries is called for
Spatial and temporal phylogeny of border disease virus in pyrenean chamois (Rupicapra p. Pyrenaica)
Border disease virus (BDV) affects a wide range of ruminants worldwide, mainly domestic sheep and goat. Since 2001 several outbreaks of disease associated to BDV infection have been described in Pyrenean chamois (Rupicapra pyrenaica pyrenaica) in Spain, France and Andorra. In order to reconstruct the most probable places of origin and pathways of dispersion of BDV among Pyrenean chamois, a phylogenetic analysis of 95 BDV 5'untranslated sequences has been performed on chamois and domestic ungulates, including novel sequences and retrieved from public databases, using a Bayesian Markov Chain Monte Carlo method. Discrete and continuous space phylogeography have been applied on chamois sequences dataset, using centroid positions and latitude and longitude coordinates of the animals, respectively.
The estimated mean evolutionary rate of BDV sequences was 2.9x10(-3) subs/site/year (95% HPD: 1.5-4.6x10(-3)). All the Pyrenean chamois isolates clustered in a unique highly significant clade, that originated from BDV-4a ovine clade. The introduction from sheep (dated back to the early 90s) generated a founder effect on the chamois population and the most probable place of origin of Pyrenean chamois BDV was estimated at coordinates 42.42 N and 1.9 E. The pathways of virus dispersion showed two main routes: the first started on the early 90s of the past century with a westward direction and the second arise in Central Pyrenees. The virus spread westward for more than 125 km and southward for about 50km and the estimated epidemic diffusion rate was about 13.1 km/year (95% HPD 5.2-21.4 km/year). The strong spatial structure, with strains from a single locality segregating together in homogeneous groups, and the significant pathways of viral dispersion among the areas, allowed to reconstruct both events of infection in a single area and of migrations, occurring between neighboring areas
Molecular analysis of hepatitis C virus infection in Bulgarian injecting drug users
Intravenous drug users constitute a group at risk for hepatitis C virus (HCV) infection. Today, no data are available on the molecular epidemiology of HCV in Bulgaria despite the fact that in recent years the incidence of acute hepatitis C infection among Bulgarian intravenous drug users increased sixfold and about 2/3 of them developed a chronic infection. The aim of this study was to determine the circulation of hepatitis C genotypes among drug users and to study the evolution and transmission history of the virus by molecular clock and Bayesian methods, respectively. Sequencing of NS5B gene showed that the genotype 3a was the most prevalent type among intravenous drug users. In the Bayesian tree, the 3a subtypes grouped in one main clade with one small cluster well statistically supported. The root of the tree was dated back to the year 1836, and the main clade from Bulgaria was dated 1960. The effective number of infections remained constant until about years 1950s, growing exponentially from the 1960s to the 1990s, reaching a plateau in the years 2000. The not significant intermixing with isolates from other countries may suggest a segregated circulation of the epidemic between 1940s and 1980s. The plateau reached by the epidemic in the early 2000s may indicate the partial success of the new preventive policies adopted in Bulgaria. J. Med. Virol. 83:1565-1570, 2011. © 2011 Wiley-Liss, Inc
Biophysical characterization of reactions associated with reverse cholesterol transport
This thesis aimed at improving our understanding of reactions relevant in the reverse cholesterol transport (RCT). RCT facilitates cholesterol homeostasis and is the most important pathway involved in cardiovascular disease. For this purpose three different projects were chosen. Thermodynamics of protein self-association and unfolding was characterized in detail at the example of Apolipoprotein A-1 (Apo A-1). Lipid binding was characterized by means of small peptides that mimic Apo A-1 function. The third project gained insight about the molecular mechanisms of ABCA1`s allocrite flopping. Apo A-1 is the main protein constituent of high density lipoprotein (HDL) and is together with ABCA1 a key player of the RCT.
Apolipoprotein A-1
Protein self-association and unfolding are two processes whose understanding is of utmost importance for the development of biological phamaceuticals as oligomerisation may alter functional properties of proteins. Apo A-1 is a perfect candidate for these investigations as it undergoes a concentration dependent self-association process and has high physiological relevance. Even though Apo A-1 is a highly investigated macromolecule, self-association was not investigated in such a comprehensive approach. Additionally, we used highly purified recombinant human Apo A-1, which was generously provided by H.-J. Schönfeld. For analyzing thermodynamics of self-association and thermal unfolding we introduced new theoretical and experimental methods
Self-association data was obtained by a combination of high sensitivity micro calorimetry and analytical ultracentrifugation. The dissociation reaction of highly concentrated and thus oligomeric Apo A-1 was followed by injection into buffer in an isothermal titration calorimeter (ITC). Dilution of the sample moved the chemical equilibrium towards monomers. Complementary, this equilibrium was analyzed by data obtained from analytical ultracentrifugation in a sedimentation equilibrium mode. If any, self-association was described in former studies as equilibrium between distinct species, for example between monomers and dimers. We introduced a cooperative self-association model that describes the equilibrium of the protein between each possible oligomer in a concentration dependent manner. Furthermore, we introduced a “binding partition function” that represents the sum of all concentrations found in the system. Together with a dissociation degree of the protein we found a link between thermodynamic data and theory of self-association. The binding partition function describes the statistical properties of the system in thermodynamic equilibrium. Hence, it is independent of the theoretical model that is utilized to describe the reaction.
Thermal unfolding of Apo A-1 was followed by circular dichroism spectroscopy (CD) and differential scanning calorimetry (DSC). We found that melting of Apo A-1 caused a transition of α–helix to β–sheet and random coiled secondary structure and appeared to be highly reversibly up to 75 °C. Thermal unfolding of Apo A-1 and in general of proteins is analyzed almost exclusively with an all-or-none model. As a powerful alternative for higly α–helical proteins such as Apo A 1, we introduced the cooperative Zimm-Bragg theory. Zimm-Bragg theory is commonly used for thermal unfolding of peptides, but fits well to our data and to data of other proteins obtained from literature.
Apo A-1 mimetic peptides
Apo A-1 was proposed as drug against cardiovascular disease. However, Apo A-1 mimetic peptides are more promising as they have to be administered in much lower dosage and are produced more easily. Understanding their lipid binding properties is essential for the estimation of in vivo effects as well as for formulation and dosage of possible drugs with these peptides. Apo A-1 structure is featured by several amphiphatic class A motif α-helices. Even though it is the main protein component of HDL, thermodynamic characterization of its lipid binding has not been achieved in detail. As a model of Apo A-1 we used two peptides (4F and P), which are featured by class A amphipathic α-helical sequences. 4F showed Apo A-1 mimetic properties in animal models and clinical studies. We used isothermal titration calorimetry to determine thermodynamic parameters of binding to POPC lipid vesicles. In order to understand this reaction several other experimental methods were used. Static and dynamic light scattering illustrated the ability of the peptides to rupture unilamellar vesicles and form micellar-like particles. In contrast, many other peptides such as cell penetrating peptides (CPPs) only partition into the membrane. This finding is in agreement with a 1:1 lipid-to-peptide stochiometry yielded from ITC data analyzed with a model of n identical binding sites. This behavior might have high physiological relevance as possible rupture of cell membranes is unwanted. Circular dichroism experiments yielded insight into structural transitions as part of the driving force of lipid binding. Associated with lipid binding is a transition of the peptide from β–sheet and random coiled to α-helical secondary structure. Tryptophan fluorescence measurements complemented the studies indicating binding to lipids as well. Thermodynamic calculation proved the structural transition of β–sheet and random coiled to α-helix as well as hydrophobic interactions as driving forces of the reaction.
Further, we studied binding of the peptide 4F to cholesterol by means of ITC. Our results suggested affinity of 4F towards cholesterol but with lower affinity compared to POPC. This might explain the formation of HDL like particles, mainly consisting of phosphocholine lipids. These particles, in turn, could bind to cholesterol with high affinity.
ABCA1
ABCA1 is an ATP binding cassette transporter that flops excess lipids of a cell to the outer membrane leaflet, where it can be picked up by Apo A-1 or HDL particles. Research in the field of ABCA1 is mainly focused on studies in cell culture and in animal models and is therefore rather indirect. Cholesterol efflux by ABCA1 was assumed to be controlled by the copy number of the transporter. The possibility of a direct modulation of the transporter activity by allocrites like in P-glycoprotein (Pgp) as well as the proposed allocrite specificity was rarely investigated in previous studies. Here, we measured the ATPase activity of inside-out vesicles prepared from ABCA1 transfected Human Embryonic Kidney 293 cells by means of a spectroscopic phosphate release assay. Aluminum fluorides were found as strong inhibitor of the nucleotide binding sites (NBD) of ABCA1 in contrast to vanadate. Furthermore, a screening for putative allocrites interacting with the transmembrane domains (TMDs) was performed with numerous compounds. Therewith we found that all compounds with a pegylated chain, a heterocyclic group and a hydrocarbon tail indicated activation of the ABCA1 ATPase
Comparative assessment of “plaque/media” change on three modalities of IVUS immediately after implantation of either everolimus-eluting bioresorbable vascular scaffold or everolimus-eluting metallic stent in Absorb II study
The purpose of the study to assess the comparability of immediate changes in plaque/media volume (PV) on three modalities of intravascular ultrasound (IVUS) after implantation of either bioresorbable vascular scaffold (BVS) or everolimus-eluting metallic stent (EES) in Absorb II Study. The two devices have different device volume and ultrasound backscattering that may interfere with the "plaque/media" assessed by three modalities on IVUS: grayscale, backscattering of radiofrequency and brightness function. In a multicenter randomized controlled trial, 501 patients with stable or unstable angina underwent documentary IVUS pre- and post- implantation. The change in plaque/media volume (PV) was categorized into three groups according to the relative PV change in device segment: PV "increased" >+5% (PVI), PV unchanged ±5% (PVU), and PV decreased <-5% (PVD). The change in PV was re-evaluated three times: after subtraction of theoretical device volume, after analysis of echogenicity based on brightness function. In 449 patients, 483 lesions were analyzed pre- and post-implantation. "PVI" was more frequently observed in BVS (53.8%) than EES group (39.4%), p = 0.006. After subtraction of the theoretical device volume, the frequency of "PVI" decreased in both BVS (36.2%) and EES (32.1%) groups and became comparable (p = 0.581). In addition, the percentage of "PVI" was further reduced in both device groups after correction for either radiofrequency backscattering (BVS 34.4% vs. EES 22.6%) or echogenicity (BVS 25.2% vs. EES 9.7%). PV change in device segment was differently affected by BVS and EES devices implantation due to their differences in device volume and ultrasound backscattering. It implies that the lumen volume was also artifactually affected by the type of device implanted. Comparative IVUS assessment of lumen and plaque/media volume changes following implantation of BVS and EES requires specific methodological adjustmen
Dynamische Ausführung von Positionstransformationen mittels OpenGL ES 2.0-Shaderprogrammen
Wegen der Forderung nach Isolation und Performanz in eingebetteten Systemen ("embedded Systems") ist ein Konzept notwendig, dass dynamisch bei laufzeitkritischen Grafikanwendungen die Positionstransformation von Vertices mit Hilfe von Vertex Shadern, während der Laufzeit übernimmt. Daher wurde in dieser Arbeit ein Konzept entwickelt, welches die Position einzelner Vertices berechnet, bevor die kompletten Rendering Befehle ausgeführt werden. Dies ist nötig um abschätzen zu können, ob die Deadlines von sicherheitskritischen Anwendungen eingehalten werden. Dazu wird in dieser Arbeit der Vertex Shader während der Laufzeit mit Hilfe von LLVM kompiliert und berechnet, für einen gegebenen Vertex dessen Position
Dynamische Ausführung von Positionstransformationen mittels OpenGL ES 2.0-Shaderprogrammen
Wegen der Forderung nach Isolation und Performanz in eingebetteten Systemen ("embedded Systems") ist ein Konzept notwendig, dass dynamisch bei laufzeitkritischen Grafikanwendungen die Positionstransformation von Vertices mit Hilfe von Vertex Shadern, während der Laufzeit übernimmt. Daher wurde in dieser Arbeit ein Konzept entwickelt, welches die Position einzelner Vertices berechnet, bevor die kompletten Rendering Befehle ausgeführt werden. Dies ist nötig um abschätzen zu können, ob die Deadlines von sicherheitskritischen Anwendungen eingehalten werden. Dazu wird in dieser Arbeit der Vertex Shader während der Laufzeit mit Hilfe von LLVM kompiliert und berechnet, für einen gegebenen Vertex dessen Position
Early phylogenetic estimate of the effective reproduction number of SARS-CoV-2
To reconstruct the evolutionary dynamics of the 2019 novel-coronavirus recently causing an outbreak in Wuhan, China, 52 SARS-CoV-2 genomes available on 4 February 2020 at Global Initiative on Sharing All Influenza Data were analyzed. The two models used to estimate the reproduction number (coalescent-based exponential growth and a birth-death skyline method) indicated an estimated mean evolutionary rate of 7.8
7 10 124 subs/site/year (range, 1.1
7 10 124-15
7 10 124) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range, 2.1-5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing
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