Hydratation und Antifouling-Oberflächen: Modellsysteme auf Basis zwitterionischer SAMs und Polysaccharide

Der Bewuchs künstlicher Oberflächen im Kontakt mit Meerwasser, das marine Biofouling, stellt aufgrund seiner ökonomischen und ökologischen Folgen seit jeher ein Problem für die Marineindustrie dar. Aufgrund des Verbotes ehemals erfolgreicher aber hochtoxischer Biozide und einem zunehmenden Umweltbewusstsein ist die Entwicklung umweltverträglicher Beschichtungen, die die initiale Anlagerung der entsprechenden Organismen beeinflussen, in den Fokus der Forschung gerückt. Da die Adhäsionsprozesse der so genannten Fouler von einer großen Bandbreite an Oberflächen¬eigenschaften beeinflusst werden, macht man sich in diesem Zusammenhang Modellsysteme mit reduzierter Komplexität zunutze, um selektiv einzelne Variablen untersuchen zu können. Gegenstand dieser Arbeit war die Präparation und Charakterisierung stark hydratisierter Modelloberflächen und die biologische Evaluierung ihrer Fouling-Resistenz. Als biologische Modellsysteme wiederum dienten stellvertretende Spezies aus allen Stadien des komplexen Biofouling-Prozesses: Cobetia marina für marine, biofilm-bildende Bakterien; Diatomeen für die schleimbildenden Mikrofouler; Zoosporen der Grünalge Ulva linza für weiche Makrofouler und Cyprislarven der Seepocke Balanus amphitrite für die harten Makrofouler. Da im realen marinen Umfeld eine Vielzahl von Faktoren ineinander greifen, wurden außerdem Feldstudien durchgeführt, um einen Überblick über diese zu gewinnen. Zwitterionische Substanzen werden aufgrund von elektrostatischen Wechselwirkungen der vorhandenen entgegengesetzten Ladungen hydratisiert. Um den Einfluss verschiedener Ladungen und ihrer Kombination auf die biologischen Modelsysteme näher zu analysieren, wurden selbst-assemblierende Monolagen (SAMs) aus Mischungen von Alkanthiolen mit unterschiedlichen geladenen Gruppen auf Gold präpariert. Die Adsorption von Testproteinen und die Anzahl adhärenter Organismen im Feldexperiment wurden durch die gleichzeitige Präsenz der entgegengesetzten Ladungsträger an unterschiedlichen Molekülen reduziert; die Ablösbarkeit der Kieselalgen erhöht. Zoosporen der Grünalge Ulva linza wiesen dagegen komplexere Adhäsionspräferenzen auf, die von der exakten Terminierung der Oberflächen abhingen. Polysaccharide sind hydrophile Biopolymere, deren Hydratation über Wasserstoffbrückenbindungen zustande kommt. Drei strukturell leicht variierende Vertreter dieser Klasse, Alginsäure (AA), Hyaluronsäure (HA) und Chondroitinsulfat (CS), wurden kovalent auf Oberflächen immobilisiert und anschließend an ihren Säuregruppen mit einem fluorierten Amin modifiziert. Dadurch wurden einerseits freie Carboxylgruppen für die Wechselwirkung mit zweiwertigen Kationen blockiert und andererseits amphiphile Eigenschaften in den hydrophilen Polymernetzwerken etabliert. Die zugrundeliegende Hypothese, dass die verminderte Fähigkeit zur Komplexierung von Ca(II)-Ionen die inerten Eigenschaften der Polysaccharidfilme im marinen Medium verbessert, konnte für AA und HA für die Adhäsion von C. marina, das Besiedlungsverhalten von U. linza und B. amphitrite und im Feldversuch bestätigt werden. Entgegengesetzt dazu verfügte das sulfatierte Polysaccharid CS im unmodifizierten Zustand über bessere antiadhäsive Eigenschaften. Als dritte Materialklasse wurden Poly(Hydroxyethylmethacrylat)-Filme, die ebenfalls durch ihr chemisches Grundgerüst eine wasserstoffbrückenbasierte Hydratation aufweisen, charakterisiert und bezüglich ihrer Proteinresistenz getestet. Für die durch oberflächeninitiierte RAFT-Polymerisation hergestellten Substrate wurde eine Schichtdickenabhängigkeit der Resistenzeigenschaften demonstriert

Measuring Lensing Magnification of Quasars by Large Scale Structure using the Variability-Luminosity Relation

We introduce a technique to measure gravitational lensing magnification using the variability of type I quasars. Quasars' variability amplitudes and luminosities are tightly correlated, on average. Magnification due to gravitational lensing increases the quasars' apparent luminosity, while leaving the variability amplitude unchanged. Therefore, the mean magnification of an ensemble of quasars can be measured through the mean shift in the variability-luminosity relation. As a proof of principle, we use this technique to measure the magnification of quasars spectroscopically identified in the Sloan Digital Sky Survey, due to gravitational lensing by galaxy clusters in the SDSS MaxBCG catalog. The Palomar-QUEST Variability Survey, reduced using the DeepSky pipeline, provides variability data for the sources. We measure the average quasar magnification as a function of scaled distance (r/R200) from the nearest cluster; our measurements are consistent with expectations assuming NFW cluster profiles, particularly after accounting for the known uncertainty in the clusters' centers. Variability-based lensing measurements are a valuable complement to shape-based techniques because their systematic errors are very different, and also because the variability measurements are amenable to photometric errors of a few percent and to depths seen in current wide-field surveys. Given the data volume expected from current and upcoming surveys, this new technique has the potential to be competitive with weak lensing shear measurements of large scale structure.Comment: Accepted for publication in Ap

Universal properties of Ising clusters and droplets near criticality

Clusters and droplets of positive spins in the two-dimensional Ising model percolate at the Curie temperature in absence of external field. The percolative exponents coincide with the magnetic ones for droplets but not for clusters. We use integrable field theory to determine amplitude ratios which characterize the approach to criticality within these two universality classes of percolative critical behavior.Comment: 23 pages, 5 figure

Geometrical vs. Fortuin-Kasteleyn Clusters in the Two-Dimensional qq-State Potts Model

The tricritical behavior of the two-dimensional $q$-state Potts model with vacancies for $1\leq q \leq4$ is argued to be encoded in the fractal structure of the geometrical spin clusters of the pure model. The close connection between the critical properties of the pure model and the tricritical properties of the diluted model is shown to be reflected in an intimate relation between Fortuin-Kasteleyn and geometrical clusters: The same transformation mapping the two critical regimes onto each other also maps the two cluster types onto each other. The map conserves the central charge, so that both cluster types are in the same universality class. The geometrical picture is supported by a Monte Carlo simulation of the high-temperature representation of the Ising model ($q=2$). In this new numerical approach, closed graph configurations are generated by means of a Metropolis update algorithm, involving single plaquettes.Comment: 23 pages, 11 figures, 2nd version: references added, introduction partly rewritten, error estimates improve

Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome

Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane of cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While K2P channels are well known to contribute to the resting membrane potential and cellular excitability, their involvement in pathophysiological processes remains largely uncharacterized. We report that de novo missense mutations in KCNK4 cause a recognizable syndrome with a distinctive facial gestalt, for which we propose the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth). Patch-clamp analyses documented a significant gain of function of the identified KCNK4 channel mutants basally and impaired sensitivity to mechanical stimulation and arachidonic acid. Co-expression experiments indicated a dominant behavior of the disease-causing mutations. Molecular dynamics simulations consistently indicated that mutations favor sealing of the lateral intramembrane fenestration that has been proposed to negatively control K+ flow by allowing lipid access to the central cavity of the channel. Overall, our findings illustrate the pleiotropic effect of dysregulated KCNK4 function and provide support to the hypothesis of a gating mechanism based on the lateral fenestrations of K2P channels

Golden gravitational lensing systems from the Sloan Lens ACS Survey. II. SDSS J1430+4105: A precise inner total mass profile from lensing alone

We study the SLACS strong lensing system SDSSJ1430+4105 at z=0.285. The lensed source (z=0.575) of this system has a complex morphology with several subcomponents. Its subcomponents span a radial range from 4 to 10kpc in the lens plane. Therefore we can constrain the slope of the total projected mass profile around the Einstein radius (R_E) from lensing alone. We measure a density profile that is slightly but not significantly shallower than isothermal at R_E. We decompose the mass of the lensing galaxy into a de Vaucouleurs (deV) component to trace the stars and an additional dark component. The spread of multiple image components over a large radial range also allows us to determine the amplitude of the deV and dark matter components separately. We get a mass to light ratio of M_deV/L_B~5.5\pm1.5M/L_sun,B and a dark matter fraction within R_E of ~20 to 40%. Modelling the star formation history assuming composite stellar populations at solar metallicity to the galaxy's photometry yields a mass to light ratio of M_star,salp/L_B~4.0_{-1.3}^{+0.6}M/L_sun,B and M_star,chab/L_B~2.3_{-0.8}^{+0.3}M/L_sun,B for Salpeter and Chabrier IMFs, respectively. Hence, the mass to light ratio derived from lensing is more Salpeter-like, in agreement with results for massive Coma galaxies and other nearby massive early type galaxies. We examine the consequences of the galaxy group in which the lensing galaxy is embedded, showing that it has little influence on the mass to light ratio obtained for the deV component of the lensing galaxy. Finally, we decompose the projected, azimuthally averaged 2D density distribution of the deV and dark matter component of the lensing signal into spherically averaged 3D density profiles. We can show that the 3D dark and luminous matter density within R_E~0.6R_eff of this SLACS galaxy is similar to the values of Coma galaxies with the same velocity dispersions.Comment: 24 pages, 21 figures, 11 tables, accepted for publication by MNRA

Multidrug Resistance and Plasmid Patterns of Escherichia coli O157 and Other E. coli Isolated from Diarrhoeal Stools and Surface Waters from Some Selected Sources in Zaria, Nigeria

We have assessed the prevalence of Escherichia coli O157 in diarrhoeal patients and surface waters from some selected sources in Zaria (Nigeria), evaluating the antibiotic susceptibility and plasmid profiles of 184 E. coli isolates, obtained from 228 water samples and 112 diarrhoeal stool specimens (collected from children aged <15 years), using standard methods. The detection rate of E. coli O157 in surface waters was 2.2% and its prevalence in children with diarrhoea was 5.4%. The most active antibiotics were gentamicin, chloramphenicol and fluoroquinolones. Seventy-nine (42.9%) of 184 E. coli isolates were resistant to four or more antibiotics. Multidrug resistance (MDR) was higher amongst aquatic isolates than the clinical isolates. Out of 35 MDR isolates (20 of which were O157 strains), 22 (62.9%) harboured plasmids all of which were no less than 2.1 kb in size. Amongst the 20 E. coli O157 strains, only seven (35.0%) contained multiple plasmids. An aquatic O157 isolate containing two plasmids was resistant to seven drugs, including ampicillin, cefuroxime, ciprofloxacin, cotrimoxazole, nalidixic acid, nitrofurantoin and tetracycline. Loss of plasmid correlated with loss of resistance to antibiotics in cured (mutant) strains selected in tetracycline (50 μg/mL)-nutrient agar plates. Our findings revealed that plasmids were prevalent in both the aquatic and clinical isolates, and suggest that the observed MDR is plasmid-mediated. The occurrence of plasmid-mediated multidrug resistant E. coli O157 in surface waters used as sources for drinking, recreation and fresh produce irrigation heightens public health concern

Geometric and stochastic clusters of gravitating Potts models

We consider the fractal dimensions of critical clusters occurring in configurations of a q-state Potts model coupled to the planar random graphs of the dynamical triangulations formulation of Euclidean quantum gravity in two dimensions. For regular lattices, it is well-established that at criticality the properties of Fortuin-Kasteleyn clusters are directly related to the conventional critical exponents, whereas the corresponding properties of the geometric clusters of like spins are not. Recently it has been observed that the latter are related to the critical properties of a tricritical Potts model with the same central charge. We apply the KPZ formalism to develop a related prediction for the case of Potts models coupled to quantum gravity and employ numerical simulation methods to confirm it for the Ising case q=2.Comment: 12 pages, 1 figure, 1 tabl

ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R–mediated apoptosis

Myeloid-derived suppressor cells (MDSCs) dampen the immune response thorough inhibition of T cell activation and proliferation and often are expanded in pathological conditions. Here, we studied the fate of MDSCs in cancer. Unexpectedly, MDSCs had lower viability and a shorter half-life in tumor-bearing mice compared with neutrophils and monocytes. The reduction of MDSC viability was due to increased apoptosis, which was mediated by increased expression of TNF-related apoptosis–induced ligand receptors (TRAIL-Rs) in these cells. Targeting TRAIL-Rs in naive mice did not affect myeloid cell populations, but it dramatically reduced the presence of MDSCs and improved immune responses in tumor-bearing mice. Treatment of myeloid cells with proinflammatory cytokines did not affect TRAIL-R expression; however, induction of ER stress in myeloid cells recapitulated changes in TRAIL-R expression observed in tumor-bearing hosts. The ER stress response was detected in MDSCs isolated from cancer patients and tumor-bearing mice, but not in control neutrophils or monocytes, and blockade of ER stress abrogated tumor-associated changes in TRAIL-Rs. Together, these data indicate that MDSC pathophysiology is linked to ER stress, which shortens the lifespan of these cells in the periphery and promotes expansion in BM. Furthermore, TRAIL-Rs can be considered as potential targets for selectively inhibiting MDSCs