107,276 research outputs found
Geschichte für morgen - Arbeitsbuch für den Geschichtsunterricht in der Sekundarstufe I, Band 3: Die Grundlagen unserer Gesellschaft (1648 - 1919) [Hauptband]
No full textGeschichte für morgen : Arbeitsbuch für d. Geschichtsunterr. in d. Sekundarstufe I / hrsg. von H. Heumann. Unter Mitarb. von J. Hampel ... - Frankfurt/Main : Hirschgraben-Verl. Bd. 3. Die Grundlagen unserer Gesellschaft (1648-1919). - 1979. - 224 S. Bd. 4. Zeitgeschichte. - 1980. - 224 S
Total and phosphorylated tau proteins: Evaluation as core biomarker candidates in frontotemporal dementia
No full textAn ever increasing number of patients with neurodegenerative disorders calls for the evaluation of potential diagnostic markers that allow an early diagnosis and an early initiation of specific therapy. Clinical diagnosis of Alzheimer's disease (AD), the most common neurodegenerative disorder, reaches 80-90% accuracy upon autopsy in specialized clinical centers. Diagnosis of AD in early clinical or preclinical stages is far less accurate, as is the differential diagnosis between AD and other primary dementias, such as frontotemporal dementia (FTD). Microtubule-associated tau protein is abnormally phosphorylated in AD and aggregates as paired helical filaments in neurofibrillary tangles. Recently, immunoassays have been developed detecting tau phosphorylated at specific epitopes in cerebrospinal fluid (CSF). Four years of clinical research consistently demonstrate that CSF phosphorylated tau (p-tau) is highly increased in AD compared to healthy controls and may differentiate AD from its most relevant differential diagnoses. Tau phosphorylated at threonine 231 (p-tau(231)) shows excellent differentiation between AD and FTD, whereas serine 181 (p-tau(181)) enhances accurate differentiation between AD and dementia with Lewy bodies. Moreover, p-tau(231) levels decline with disease progression, correlating with cognitive performance at baseline. Total tau (t-tau) is regarded as a general marker of neurodegeneration for evaluation in future population-based studies. p-tau(231) and p-tau(181) yield excellent discrimination between AD and non-AD dementias including FTD, exceeding the differential diagnostic and prognostic accuracy of t-tau. Therefore, p-tau is a core biological marker candidate for future evaluation in large national and international multicenter networks. Copyright (C) 2004 S. Karger AG, Basel
Enantiomerisation of tetrahedral homochiral [M4L6] clusters: Synchronised four Bailar twists and six atropenantiomerisation processes monitored by temperature-dependent dynamic H-1 NMR spectroscopy
No full textTemperature-dependent H-1 NMR studies prove homochiral, racemic [(Delta,Delta,Delta,Delta)/(Lambda,Lambda,Lambda,Lambda]-[(NH4)(4)boolean AND[Mg-4(L-1)(6)]} (1) to be kinetically stable on the NMR timescale. Due to steric reasons, rotation around the central C-C single bond in (L-1)(2-) is blocked, which prevents 1 from enantiomerisation. Most interestingly, however, the H-1 NMR spectrum of racemic 2a reveals dynamic temperature dependence. This phenomenon can be explained by simultaneous Bailar twists at the four octahedrally coordinated magnesium centres, synchronised with the sterically unhindered atropenantiomerisation processes around the C-C single bonds of the six ligands (L-2)(2-), leading to the unprecedented enantiomerisation (Delta,Delta,Delta,Delta)-2a reversible arrow (Lambda,Lambda,Lambda,Lambda)-2a. The profound nondissociative rearrangement occurs without the formation of diastereoisomers. Supplementary support for the interpretation of the temperature-dependent dynamic H-1 NMR spectra of 2 a is presented by additional studies of [(Delta,Delta,Delta,Delta)/(Lambda,Lambda,Lambda,Lambda]-{EtNH3)(4)boolean AND[Mg-4(L-2)(6)]} (2b). In 2 a and 2b, the ether methylene protons exhibit identical temperature dependence. However, with addition, the methylene protons of the ethyl ammonium groups of 2b display similar temperature dependence as the ligand ether methylene protons
Imaging Epigenetics in Alzheimer's Disease
No full textSporadic Alzheimer's disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and behavioral decline. This decline includes reductions in the activities of daily living, quality of life, independence, and life expectancy. Evolving lines of research suggest that epigenetic mechanisms may play a crucial role during AD development and progression. Epigenetics designates molecular mechanisms that alter gene expression without modifications of the genetic code. This topic includes modifications on DNA and histone proteins, the primary elements of chromatin structure. Accumulating evidence has revealed the relevant processes that mediate epigenetic modifications and has begun to elucidate how these processes are apparently dysregulated in AD. This evidence has led to the clarification of the roles of specific classes of therapeutic compounds that affect epigenetic pathways and characteristics of the epigenome. This insight is accompanied by the development of new methods for studying the global patterns of DNA methylation and chromatin alterations. In particular, high-throughput sequencing approaches, such as next-generation DNA sequencing techniques, are beginning to drive the field into the next stage of development. In parallel, genetic imaging is beginning to answer additional questions through its ability to uncover genetic variants, with or without genome-wide significance, that are related to brain structure, function and metabolism, which impact disease risk and fundamental network-based cognitive processes. Neuroimaging measures can further be used to define AD systems and endophenotypes. The integration of genetic neuroimaging methods with epigenetic markers in humans appears promising. This evolving development may lead to a new research discipline - imaging epigenetics - that will provide deeper insight into the causative pathogenetic and pathophysiological pathways through which genes and environment interrelate during life and impact human brain development, physiology, aging and disease. This knowledge may open doors for the development of novel biomarkers and preventive and disease-modifying treatments
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Geographic profiling in Nazi Berlin: fact and fiction
No full textGeographic profiling uses the locations of connected crime sites to make inferences about the probable location of the offender’s ‘anchor point’ (usually a home, but sometimes a workplace). We show how the basic ideas of the method were used in a Gestapo investigation that formed the basis of a classic German novel about domestic resistance to the Nazis during the Second World War. We use modern techniques to re-analyse this case, and show that these successfully locate the Berlin home address of Otto and Elise Hampel, who had distributed hundreds of anti-Nazi postcards, after analysing just 34 of the 214 incidents that took place before their arrest. Our study provides the first empirical evidence to support the suggestion that analysis of minor terrorism-related acts such as graffiti and theft could be used to help locate terrorist bases before more serious incidents occur
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