Transthyretin Mimetics as Anti‐β‐Amyloid Agents: A Comparison of Peptide and Protein Approaches

β‐Amyloid (Aβ) aggregation is causally linked to neuronal pathology in Alzheimer's disease; therefore, several small molecules, antibodies, and peptides have been tested as anti‐Aβ agents. We developed two compounds based on the Aβ‐binding domain of transthyretin (TTR): a cyclic peptide cG8 and an engineered protein mTTR, and compared them for therapeutically relevant properties. Both mTTR and cG8 inhibit fibrillogenesis of Aβ, with mTTR inhibiting at a lower concentration than cG8. Both inhibit aggregation of amylin but not of α‐synuclein. They both bind more Aβ aggregates than monomer, and neither disaggregates preformed fibrils. cG8 retained more of its activity in the presence of biological materials and was more resistant to proteolysis than mTTR. We examined the effect of mTTR or cG8 on Aβ binding to human neurons. When mTTR was co‐incubated with Aβ under oligomer‐forming conditions, Aβ morphology was drastically changed and Aβ‐cell deposition significantly decreased. In contrast, cG8 did not affect morphology but decreased the amount of Aβ deposited. These results provide guidance for further evolution of TTR‐mimetic anti‐amyloid agents.     

trans Fatty Acids in Colostrum,Mature Milk and Diet of Lactating Adolescents

The purpose of this study was to investigate the trans fatty acids (TFA) content and distribution in colostrum, mature milk, and diet of adolescent mothers, after TFA declaration in food labels became mandatory in Brazil. Participants were healthy adolescents (n 54, 15–19 years, 1–90 days postpartum) practicing exclusive breastfeeding. Milk samples were collected 3 days after delivery (colostrum) and in the third month postpartum (mature milk) by hand expression. The fatty acid composition of the milk samples was determined by gas chromatography. TFA intake corresponded to 1.23 % of total energy value. Total 18:2 TFA accounted for less than 0.5 % of the energy intake. The amount of total 18:1 TFA (mean ± SEM) was 1.9 % ± 0.14 in colostrum and 1.5 % ± 0.2 in mature milk. The total content of n‐3 PUFA was inversely correlated with the total content of 18:1 TFA in colostrum. Both in colostrum and in mature milk, vaccenic acid (11t‐18:1) was found to be the most abundant 18:1 trans isomer, followed by elaidic acid (9t‐18:1), whereas rumenic acid (9c,11t‐18:2 CLA) was the predominant 18:2 trans isomer. In conclusion, the levels of TFA of industrial sources found in the mother's diet and breast milk (colostrum and mature milk) showed a decrease in relation to those observed in studies conducted prior to the TFA labeling resolution in Brazil. However, the current low intake levels of n‐3 LCPUFA and DHA content in the milk of lactating adolescents may be insufficient for supporting adequate neurological development of the infants.     

Semantische Informationsextraktion in medizinischen Informationssystemen

Zusammenfassung Dieser Artikel beschreibt einige Erfahrungen und typische Problemstellungen mit Textmining in der Medizin und gibt einen Einblick in aktuelle und zukünftige Herausforderungen in Forschung & Entwicklung. Interessant ist n?mlich, dass auch im ,,Multimedia-Zeitalter“ die meiste Information immer noch als ,,Text“ vorliegt. Mithilfe von statistischen und linguistischen Verfahren wird mit sogenannter ,,Textmining-Software“ versucht, aus Freitexten Information ,,heraus zu schürfen“ (deshalb ,,Textmining“). Allerdings ist es damit noch nicht genug. Der n?chste Schritt besteht darin, die Information sowohl nutzbar als auch brauchbar zu machen. Die jeweiligen End-Benutzerinnen und End-Benutzer müssen in die Lage versetzt werden, auf der Basis der gewonnenen Information deren Wissen zu erweitern. In unserem konkreten Fall sollen damit Entscheidungen im Rahmen ?rztlichen Handelns unterstützt werden. Probleml?sungen in diesem Bereich erfordern eine holistische Sicht- und Herangehensweise. Daher wird es immer wichtiger, Erkenntnisse aus Informatik und Psychologie zusammenflie?en zu lassen und auf systemischer Ebene technologisch umzusetzen.     

The digital divide and t-government in the United States: using the technology acceptance model to understand usage

This paper applies the technology acceptance model to explore the digital divide and transformational government (t-government) in the United States. Successful t-government is predicated on citizen adoption and usage of e-government services. The contribution of this research is to enhance our understanding of the factors associated with the usage of e-government services among members of a community on the unfortunate side of the divide. A questionnaire was administered to members, of a techno-disadvantaged public housing community and neighboring households, who partook in training or used the community computer lab. The results indicate that perceived access barriers and perceived ease of use (PEOU) are significantly associated with usage, while perceived usefulness (PU) is not. Among the demographic characteristics, educational level, employment status, and household income all have a significant impact on access barriers and employment is significantly associated with PEOU. Finally, PEOU is significantly related to PU. Overall, the results emphasize that t-government cannot cross the digital divide without accompanying employment programs and programs that enhance citizens’ ease in using such services.     

Cerebellar cortical degeneration disrupts discrimination learning but not delay or trace classical eyeblink conditioning.

The authors investigated classical eyeblink conditioning in a relatively rare patient, B.R., with extensive cerebellar cortical atrophy and marked sparing of the dentate nucleus. Patient B.R.'s ability to acquire and extinguish simple associations (delay and trace conditioning tasks) as well as her ability to acquire more complex associations (temporal and simple discrimination tasks) were examined. There are 2 primary findings from this study. First, B.R. showed normal acquisition and extinction in delay and trace conditioning. Second, she demonstrated a complete inability to learn associative discriminations, even in the case of a simple 2-tone discrimination within the context of a delay paradigm. The latter finding was unexpected because of the sparing of her deep cerebellar nuclei. These data suggest that the cerebellar cortex, or pathways traversing cerebellar cortex, play an important role in classical eyeblink discrimination learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Status of ceramic breeder pebble bed thermo-mechanics R&D and impact on breeder material mechanical strength

Among the international fusion solid breeder blanket community, there exists steady progress on the experimental, phenomenological, and numerical characterizations of the pebble bed effective thermo physical and mechanical properties, and of thermomechanic state of the bed under prototypical operating conditions. This paper summarizes recent achievements in pebble bed thermomechanics that were carried out by members of the IEA Fusion Nuclear Technology Subtask I Solid Breeding Blanket. A major goal is on developing predictive capability while identifying a pre-conditioned equilibrium stress state that would warrant pebble bed integrity during operations. The paper reviews and synthesizes existing computational modeling approaches for pebble bed thermomechanics prediction, and differentiating points of convergence/divergence among existing approaches. The progress toward modeling benchmark is also discussed. These advancements have led to a framework to help navigate future research.     

Relevance of peat-draining rivers for the riverine input of dissolved iron into the ocean

Peat bogs have the ability to produce strong chelate ligands (humic and fulvic acids) which enhance the weathering rates of iron-silicate minerals and greatly increase the solubility of the essential trace metal iron in river water. Fluvial networks link peat bogs with the ocean, and thus terrestrial-derived fulvic-iron complexes fuel the ocean's biological productivity and biological carbon pump, but understanding this role is constrained by inconsistent observations regarding the behaviour of riverine iron in the estuarine mixing zone, where precipitation reactions remove iron from the water column. We applied a characterization of the colloidal iron carriers in peatland-draining rivers in North Scotland, using field-flow fractionation (FFF), in combination with end-member mixing experiments of river water sampled near the river mouth and coastal seawater using a ⁵⁹Fe radiotracer method. According to our results, the investigated river contributed “truly dissolved” Fe concentrations of about 3300 nmol L^− 1 to the ocean which is nearly two orders of magnitude higher than the dissolved iron contribution of the “average world” river (∼ 40 nmol L^− 1). Thus we conclude that peatland-draining rivers are important sources of dissolved iron to the ocean margins. We propose highly electrostatic and sterical stabilized iron-organic matter complexes in the size range of < 2 kDa to be responsible for iron transport across the estuarine mixing zone.     

Automated Karl Fischer titration for liquid samples – Water determination in edible oils

In the field of food analysis, rapid measurements and results are generally of high importance. The Karl Fischer titration (KFT), a chemical method for determining water content, and its automated performance enhance rapidity by giving the opportunity to deal with more samples in less time; automated sequences can include different determination methods and sample treatments. Moreover, automation can improve reproducibility and precision.     

Characteristics of WWTP sludge after drying in greenhouse for agricultural purposes

The sludge generated by sewage treatment which meets regulatory standards can be used in agriculture. With this understanding, the focus of this study is the evaluation of the agricultural characteristics and inorganic substances in excess activated sludge, which was subjected to drying in a greenhouse. The variables (factor) evaluated during the drying process were: type of sludge (digested or not digested), addition of lime to the sludge, and the physical layout and rotation of sludge in the greenhouse. The parameters monitored for this assessment were moisture, volatile solids and pH. The greenhouse cover and sides were made of translucent plastic to allow the penetration of solar radiation and prevent water from entering. A impermeable floor was used. The sludge was generated in sewage treatment plants located in the metropolitan region of Grande Vitória, Espírito Santo, Brazil. The solar drying of wastewater sludge in a greenhouse presented satisfactory results.