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[Abstract fehlt

Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs-Aβ) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-Aβ were able to interfere with Aβ peptide toxicity, but NAbs-Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates

Two-frame 3D particle tracking

A whole-field three-dimensional (3D) particle tracking velocimetry (PTV) tool for diagnostics in fluid mechanics is presented. Specifically, it is demonstrated why and when PTV is the natural choice in 3D applications compared to particle image velocimetry (PIV). Three different tracking methods are investigated, namely the nearest neighbour, the neural network and the relaxation method. In order to demonstrate the use of PTV for 3D applications, the selected tracking schemes are implemented for use with the defocusing digital particle image velocimetry (DDPIV) technique. The performance of the tracking algorithms is evaluated based on synthetic 3D information. Furthermore, the potential benefit of a merging between the PIV and PTV approaches is explored within the DDPIV framework. The results show that the relaxation tracking method is the most robust and efficient, while the combined PIV/PTV analysis brings significant improvements solely with the neural network scheme. In terms of errors, PTV is found to be more sensitive to particle reconstruction errors than the DDPIV cross-correlation analysis

Three-dimensional flow effects on forced convection heat transfer in a channel with stepwise-varying width

A numerical investigation based on the finite volume methodology of the three-dimensional laminar flow and conjugate heat transfer inside a plate-fin heat sink with stepwise-varying channel width is presented. Results are obtained for the three-dimensional flow developed in the vicinity of the flow contraction as manifested by the existence of two pairs of contra-rotating longitudinal vortices, one at the corners of the fin leading edge and the other at the flow separated regions. The topology of the flow is thoroughly examined and the contributions of the endwalls and the front surface of the flow-contracting fin to the mechanisms that cause the emergence of the three-dimensionality are determined. It is established that the corner longitudinal vortices are in fact horseshoe vortices, which emerge due to the deceleration effect of the fin front surface on the oncoming fluid. Furthermore, the interaction between the corner longitudinal vortices and the downstream recirculation bubble formed over the fin tip is also elucidated. The analysis covers a wide range of flow conditions within the laminar region in order to monitor the effect of the Reynolds number on the flow topology and to verify that the flow remains symmetrical in this region. From the numerical results, it is deduced that the recirculation downstream of the flow contraction has a beneficial impact on the heat sink thermal performance, a fact quantified through the local Nusselt number distributions

The curse of the uncultured fungus

The international DNA sequence databases abound in fungal sequences not annotated beyond the kingdom level, typically bearing names such as “uncultured fungus”. These sequences beget low-resolution mycological results and invite further deposition of similarly poorly annotated entries. What do these sequences represent? This study uses a 767,918-sequence corpus of public full-length fungal ITS sequences to estimate what proportion of the 95,055 “uncultured fungus” sequences that represent truly unidentifiable fungal taxa – and what proportion of them that would have been straightforward to annotate to some more meaningful taxonomic level at the time of sequence deposition. Our results suggest that more than 70% of these sequences would have been trivial to identify to at least the order/family level at the time of sequence deposition, hinting that factors other than poor availability of relevant reference sequences explain the low-resolution names. We speculate that researchers’ perceived lack of time and lack of insight into the ramifications of this problem are the main explanations for the low-resolution names. We were surprised to find that more than a fifth of these sequences seem to have been deposited by mycologists rather than researchers unfamiliar with the consequences of poorly annotated fungal sequences in molecular repositories. The proportion of these needlessly poorly annotated sequences does not decline over time, suggesting that this problem must not be left unchecked

All-particle cosmic ray energy spectrum measured with 26 IceTop stations

We report on a measurement of the cosmic ray energy spectrum with the IceTop air shower array, the surface component of the IceCube Neutrino Observatory at the South Pole. The data used in this analysis were taken between June and October, 2007, with 26 surface stations operational at that time, corresponding to about one third of the final array. The fiducial area used in this analysis was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV measured for three different zenith angle ranges between 0{\deg} and 46{\deg}. Because of the isotropy of cosmic rays in this energy range the spectra from all zenith angle intervals have to agree. The cosmic-ray energy spectrum was determined under different assumptions on the primary mass composition. Good agreement of spectra in the three zenith angle ranges was found for the assumption of pure proton and a simple two-component model. For zenith angles {\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on composition assumption. Spectral indices above the knee range from -3.08 to -3.11 depending on primary mass composition assumption. Moreover, an indication of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure

Heat transfer and fluid flow over microscale backward and forward facing step: A review

Research on convective heat transfer in the microscale backward-facing step (MBFS) and microscale forward-facing step (MFFS) has been extensively conducted in the past decade. This review summarizes numerous researches on the three topics; the first section focuses on studying the effect of the geometry on the fluid flow and heat transfer behavior. The second and the third sections concentrate on the effect of the inclination angle and the flow regime on the fluid flow and heat transfer enhancement. The purpose of this article is to get a clear view and detailed summary of the influence of several parameters such as the geometrical specifications, type of fluids and boundary conditions. The enhancement in the Nusselt number is the main target of such research where correlation equations were developed in numerical and experimental studies are reported

Wahrnehmung von Biotinmangel durch Saccharomyces cerevisiae

Biotin ist ein wasserlösliches Vitamin, es kann von fast allen S. cerevisiae-Stämmen nicht de novo synthetisiert werden und dient als prosthetische Gruppe bei Carboxylierungsreaktionen. Es war bekannt, dass die Bäckerhefe bei einem Mangel an Biotin mit einer Expressionssteigerung des Biotintransportergens VHT1 reagiert [Stolz et al. (1999), J Biol Chem 274, 18741-18746]. Mit Hilfe von Sequenzvergleichen konnte in dieser Arbeit in den Promotoren der meisten Gene aus dem Biotinmetabolismus ein konserviertes palindromisches DNA-Element identifiziert werden. Dieses ist als UASBIO notwendig und hinreichend für eine biotinabhängige Regulation. Western Blot- und Reportergenanalysen, untermauert durch Daten aus Microarray- und Nothern Blot-Experimenten, zeigten außerdem, dass neben VHT1 auch die anderen Gene des Biotinmetabolismus bei Biotinmangel aktiviert werden. Der Plasmamembrantransporter Vht1p ist nicht an der Wahrnehmung von Biotin beteiligt. Deletionsmutanten wiesen zwar eine Aktivierung der biotinregulierten Gene auf, dieser Effekt war aber nach der Gabe von Biotinvorstufen, die unabhängig von Vht1p aufgenommen und intrazellulär in Biotin umgewandelt werden, nicht länger zu beobachten. Dabei wurde auch die Wahrnehmung extrazellulären Biotins ausgeschlossen. Im Gegensatz zur Situation beim Ausfall anderer biotintragender Proteine wurde ein Biotinmangelsignal bei einer Deletion beider Pyruvatcarboxylasen, Pyc1p und Pyc2p, komplett verhindert. Somit sind die Pyruvatcarboxylasen essentiell für die Wahrnehmung von Biotin. Der genaue Funktionsmechanismus konnte allerdings noch nicht geklärt werden. Aufgrund dieses Resultats wurde aber neben Vht1p auch der Biotin-Protein-Ligase Bpl1p, einem essentiellen Enzym, welches Biotin auf die Zielproteine überträgt, nur eine indirekte Rolle in der Biotinwahrnehmung zugeschrieben. Wie bei vht1(delta)-Mutanten zeigten bpl1-Mutanten ebenfalls eine deutliche Expressionssteigerung der Biotingene, besaßen aber im Gegensatz zu vht1(delta)-Mutanten normale Konzentrationen an freiem intrazellulären Biotin. Dieses ist deshalb für die Wahrnehmung von Biotinmangel nicht relevant. Um unbekannte Glieder der Biotinsignalkette zu finden, wurde zum einen ein Reporterstamm mit EMS mutagenisiert und zum anderen mit einer multi-copy Genbank transformiert. Es konnten jeweils Klone mit einem konstitutiven Biotinmangelsignal (BHB, �blind for high biotin�) isoliert werden. Nach verschiedenen Tests zur Charakterisierung der Mutanten stehen 15 EMS-Klone für nachfolgende Komplementationstests zur Verfügung. Im anderen Ansatz konnte für keines der sequenzierten Genbankplasmide eine Beteiligung in der Biotinsignalkette nachgewiesen werden. Nichtsdestotrotz zeigt die hier erfolgte Identifizierung von TIS11, dem Gen eines eisenabhängigen Regulatorproteins, eine weitere interessante Verbindung von Biotin- und Eisenmetabolismus auf