Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease

Proteomic analysis of cerebrospinal fluid (CSF) holds great promise in understanding the progression of neurodegenerative diseases, including Alzheimer's disease (AD). As one of the primary reservoirs of neuronal biomolecules, CSF provides a window into the biochemical and cellular aspects of the neurological environment. CSF can be drawn from living participants allowing the potential alignment of clinical changes with these biochemical markers. Using cutting-edge mass spectrometry technologies, we perform a streamlined proteomic analysis of CSF. We quantify greater than 700 proteins across 10 pairs of age- and sex-matched participants in approximately one hour of analysis time each. Using the paired participant study structure, we identify a small group of biologically relevant proteins that show substantial changes in abundance between cognitive normal and AD participants, which were then analyzed at the peptide level using parallel reaction monitoring experiments. Our findings suggest the utility of fractionating a single sample and using matching to increase proteomic depth in cerebrospinal fluid, as well as the potential power of an expanded study.     

Tod des Körpers oder Tod der Person?

Definition of the problem

Within the current philosophical debate on the adequate definition of human death, death is defined either as the death of the body or the death of the person. However, the application of these notions leads to several practical conflicts, which can be seen first and foremost in the brain-death debate and the discussions on how to increase organ donation.

Arguments

The conflicts are based in both a dualistic and objectivistic notion of the human being which are implied in both definitions of death. In order to solve these conflicts, we are in need of a nondualistic concept of human being which at the same time enables us to elaborate a first- and second-person perspective on death. On the basis of Helmuth Plessner’s philosophical anthropology, such an integrative concept of death can be developed.

Conclusion

Following this concept, it seems reasonable to abandon the brain-death criterion as the criterion for human death and to fundamentally reform the current information campaigns for organ donation.

     

Temperature and processing effects on lithium ion conductivity of solution-deposited lithium zirconium phosphate (LiZr2P3O12) thin films

Lithium zirconium phosphate (LiZr₂P₃O₁₂) thin films have been prepared on platinized silicon substrates via a chemical solution deposition approach with processing temperatures between 700°C and 775°C. Films that were subject to a single high-temperature anneal were found to crystallize at temperatures above 725°C. Crystallization was observed in films annealed after each deposited layer at 700°C and above. In both cases, grain size was found to increase with annealing temperature. Ion conductivity was found to increase with annealing temperature in singly annealed films. In per-layer annealed films ion conductivity was found to initially increase then decrease with increasing annealing temperature. A maximum ion conductivity of 1.6 × 10⁻⁶ S/cm was observed for the singly annealed 775°C condition, while a maximum ion conductivity of 5.8 × 10⁻⁷ S/cm was observed for the 725°C per-layer annealed condition. These results are consistent with an increasing influence of cross-plane, internal interface resistance and vapor phase carrier loss in the per-layer annealed samples. This work demonstrates that post-deposition processing methods can strongly affect the ion conducting properties of LiZr₂P₃O₁₂ thin films.     

Hot isostatic pressed pyrochlore glass-ceramics: Revealing structure insides at the reaction interface

As potential waste forms for immobilizing actinide-rich radioactive wastes, Eu₂Ti₂O₇ (Eu as a surrogate for minor actinides) pyrochlore glass-ceramics were fabricated via hot isostatic pressing (HIPing) at 1200°C. The structure and microstructure at the reaction interface between the glass-ceramic waste form and the stainless steel (SS) canister under HIPing conditions were carefully investigated with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and synchrotron single crystal X-ray diffraction (SC-XRD). The interactions at the reaction interface led to the formations of a ~10-µm-thick Cr₂O₃ layer as the oxidation front of the SS and a layer of a mixed oxide phase (Eu_1.25SiCr_0.8Ti_1.2O_7.5) on the glass-ceramic side of the reaction interface. The crystal structure of such a unique mixed oxide phase was revealed indubitably with a combination of synchrotron SC-XRD and TEM assisted with a focused ion beam (FIB) SEM system. The improved structural understanding of the reaction interface will help to support the utilization of HIPing as a versatile hot consolidation process for the treatment of radioactive wastes.     

Upcycling by grafting onto semi-crystalline polymers using supercritical CO2

The creation of graft copolymers by selectively grafting a second polymer to the amorphous fraction of a semi-crystalline polymer in supercritical CO₂ is demonstrated herein. The graft copolymer is synthesized by free radical polymerization of a vinyl monomer within the semi-crystalline polymer below its melt temperature. Such conditions afford selective grafting on the amorphous regions (block “B”) while leaving the crystalline domains (block “A”) unmodified. Accordingly, unique A-B, A-B-A, A-B-A-B-A, and so forth. block structures are formed. In this work, styrene is polymerized within polyamide 6, polyethylene terephthalate, and isotactic polypropylene. Purification of these material is performed to remove the un-grafted homopolymer, allowing for determination of the graft yield, the portion of polymer which covalently bonds to the semi-crystalline matrix. Grafting yields achieved in polyamide 6, polyethylene terephthalate, and isotactic polypropylene were 98%, 59%, and 15%, respectively. Property enhancements were observed upon further characterization of polystyrene-polyamide 6 copolymers, including high glass transition temperatures, the ability to be remelted, and tunable grafting molecular weight. Additionally, hydrophobicity is controlled by varying polystyrene composition. The remarkable range of accessed properties demonstrates this as a potential route to upcycling plastics.     

Examination of superplastic forming combined with diffusion bonding for titanium: Perspective from experience

Superplastic forming (SPF) combined with diffusion bonding (DB) has been used successfully for the fabrication of titanium aerospace hardware. Many of these applications have been for military aircraft, whereby a complex built-up structure has been replaced with monolithic parts. Several methods for applying the two- and four-sheet titanium SPF/DB processes have been devised, including the welding of sheets prior to forming and the use of silk-screened stop-off (yttria) to prevent bonding where it is undesirable. Very little progress has been made in the past few years toward understanding and modeling the SPF/DB process using constitutive equations and data by laboratory testing. Concerns that engineers face in designing for fatigue life, acceptable design loads, and damage tolerance are currently being studied, but the database is very limited. This is a summary of past work found in the literature and forms the foundation for additional research. This paper was presented at the International Symposium on Superplasticity and Superplastic Forming sponsored by the Manufacturing Critical Sector at the ASM International AeroMat 2004 Conference and Exposition, June 8–9, 2004, in Seattle, WA. The symposium was organized by Daniel G. Sanders, The Boeing Company.     

Effects of carbon content and solidification rate on thermal conductivity of grey cast iron

The thermal conductivity or diffusivity of pearlitic grey irons with various carbon contents is investigated by the laser flash method. The materials are cast in controlled thermal environments and produced in three dissimilar cooling rates. The cooling rate together with the carbon content largely influence the thermal conductivity of grey iron. Linear relationships exist between the thermal conductivity and the carbon content, the carbon equivalent and the fraction of former primary solidified austenite transformed into pearlite. The work shows that optimal thermal transport properties are obtained at medium cooling rates. Equations describing the thermal conductivity of pearlite,solidified as pre-eutectic austenite, and the eutectic of grey iron are derived. The thermal conductivity of pearlitic grey iron is modeled at both room temperature and elevated temperature with good accuracy.     

Oxidation of ternary Co-Cr-W alloys

Oxidation rates in air at 1000–1250°C are reported for a series of Co-Cr-W alloys with 34–40 wt. % Cr and up to 10 wt. % W. Alloys with larger W contents exhibited slower oxidation rates and their parabolic rate constants agreed well with those for binary and ternary, Cr₂O₃ protected, Ni-base and Co-base alloys in the Co-Cr and Ni-Cr-W systems. The resulting scales were characterized by optical and scanning electron metallography, and electron microprobe analysis. The favorable effect of W additions to a Cr₂O₃-forming Co-Cr base alloy was the opposite of that reported for Ni-Cr-W alloys. The resupply of Cr to a Cr-depleted matrix beneath a protective CrO₃ scale is achieved by the dissolution (denuding) of Cr-rich second phases in the Co-Cr-W alloys. Thus, the internal oxidation of Cr beneath the Cr₂O₃ scale is avoided for high W alloys. No catastrophic failure by liquid phase formation was observed for high-W alloys oxidized 20 hr at 1250°C.