In Vivo Detection of Amyloid-β Deposits Using Heavy Chain Antibody Fragments in a Transgenic Mouse Model for Alzheimer's Disease

This study investigated the in vivo properties of two heavy chain antibody fragments (VHH), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-β deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled VHH in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Aβ was examined in more detail with fluorescently labeled VHH by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All VHH showed rapid renal clearance (10–20 min). Twenty-four hours post-injection 99mTc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for 99mTc-ni3A or DTPA(111In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled VHH, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both VHH showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that VHH detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Aβ deposits

Flow visualization and supersonic combustion studies of an acoustically open strut cavity

In this study, the supersonic flow over strut cavities was experimentally studied to understand flow features. Instantaneous schlieren imaging in non-reacting flow experiments exhibited the seven types of waves associated with cavity pressure oscillations and the formation of unstable shear layers on both sides. The shear layers moved in and out in synchronous and asynchronous modes at the trailing edge of the strut cavities. The symmetrical wave structure appeared on both sides in the synchronous mode, whereas the shear layers appeared in different stages of the cavity pressure oscillation cycle in the asynchronous mode, resulting in an asymmetrical wave structure. The pressure waves generated at the trailing edge of the strut cavities perturbed the shear layers during their movement toward the leading edge, creating a wavy shear layer with alternate troughs and crests. The pressure oscillations of the strut cavities had high-amplitude cavity modes with broadband noises, and their amplitude decreased from the trailing edge to the leading edge. The estimated recovery factor using the time lag between the signals of the leading and trailing edges showed that the flow inside the strut cavities was low subsonic. The measured dominant pressure oscillation modes had a closer match with the Rossiter modes. The pressure coefficient demonstrated that fluid accumulation inside the cavity increased with an increase in the aspect ratio. Furthermore, a higher fluid mass accumulated at the trailing edge than at the leading edge, and the difference in fluid accumulation increased with an increase in the aspect ratio. Supersonic combustion experiments with strut cavities showed that the strut cavity stabilized the flame. Moreover, the addition of an acoustically open strut cavity ahead of the flame-stabilizing cavity advanced the heat release location upstream

Mobile ion transport pathways in (LiBr) x[(Li 2O) 0.6(P 2O 5) 0.4] (1-x) glasses

10.1007/s10008-010-1005-0Journal of Solid State Electrochemistry14101781-178

Intermediate species detection in a morpholine flame: contributions to fuel-bound nitrogen conversion from a model biofuel

Nau P, Seipel A, Lucassen A, Brockhinke A, Kohse-Höinghaus K. Intermediate species detection in a morpholine flame: contributions to fuel-bound nitrogen conversion from a model biofuel. EXPERIMENTS IN FLUIDS. 2010;49(4):761-773.A slightly fuel-rich (I broken vertical bar = 1.3) premixed laminar flat morpholine/oxygen/argon flame at 40 mbar was studied with cavity ring-down spectroscopy (CRDS). Morpholine as a secondary amine was considered as a prototypical nitrogenated biofuel. To contribute to the investigation of fuel-nitrogen conversion chemistry in this flame, absolute mole fraction profiles of CH, CN, and NH2 were determined. To our knowledge, this is the first study reporting quantitative mole fractions of these radicals from CRDS in a low-pressure flame of a model biofuel. The species profiles are discussed in combination with some relevant intermediates from molecular beam mass spectrometry, determined in this flame very recently (Lucassen et al., Proc Combust Inst 32(1):1269-1276, 2009). Some relative species profiles were also determined in flames of further amines to facilitate comparison. The results demonstrate that NH3- and HCN-related chemistry occurs in different regions of this flame. HCN production is considerable, and NO is found in the exhaust gases in percent-level concentrations. To monitor the combustion status, chemiluminescence is increasingly being applied as an intrinsic low-cost sensor. We believe to present the first chemiluminescence measurements in a flame of a prototypical nitrogenated biofuel, reporting relative emission intensities for five excited-state species. The shapes and maximum positions of the ground- and excited-state profiles show interesting differences, especially for the CN radical, which must be the consequence of different reaction pathways

Structural Insight into Transition Metal Oxide containing glasses by Molecular Dynamic Simulations

In the last years, glass research focused particular attention on transition metal oxide containing systems for semi-conductive applications, for instance glasses for solid-state devices and secondary batteries. In glass matrices, transition metal ions show multiple oxidation states that lead to peculiar structures and to highly complex systems, which produce interesting optical, electrical and magnetic properties. Computational methods have been largely employed as complementary tool to experimental techniques, in order to improve the knowledge on the materials and their performances. In this work, Molecular Dynamic (MD) simulations have been performed on a series of alkali vanado-phosphate glasses in order to gain deep comprehension of the glass structure. The short and medium range order of the V4+ and the V5+ sites in terms of coordination, pair distribution function, V\u2013O\u2013V linkages, bridging and non-bridging oxygen distributions were calculated and discussed. Finally, the comparison between MD and experimental results shows a very good agreement allowing the validation of the computational models and highlights the correlations between the structure and the conduction mechanism in these glasses. This allows enriching the know-how on these glass systems that result still ambiguous until now