julilili42/papers huggingface dataset:
Exploring the Neural Pattern in EEG Records of Material-specific Memory Maintenance by Deep Learning
2018-07-01

In this paper, a classification performance comparison among several machine learning algorithms is presented, utilizing different frequency features (theta, alpha, low beta, high beta, low gamma and high gamma) which are extracted from material-specific visual memory maintenance EEG records of 20 volunteers. Decision tree, Support Vector Machine(SVM), Convolutional Neural Network(CNN) and Deep Forest (DF) are used to classify. As shown in our results, deep forest improved the classification accuracy by 9.75% in low beta (14- 20Hz) while distinguishing Face from House and 1.25% with 50% standard deviation reduction in alpha (8-12Hz) while distinguishing Digit from Letter. Those results proved that deep learning has certain potential advantage over traditional machine learning in small-sample EEG analysis. Low beta and alpha band are found to be important features in material-specific memory maintenance in graph-specific and alphanumeric-specific conditions respectively.
The age of stored erythrocytes influences methaemoglobin formation when circulated in a heart-lung machine model.
2018-07-01

The formation of storage lesions, which is caused especially by oxidative stress, is a well-known process associated with prolonged storage of erythrocytes1–3. However, its relevance for patients receiving a transfusion is still under discussion4,5. Erythrocyte concentrates are frequently required by patients managed with extracorporeal circulatory systems, such as a heart-lung machine (HLM), extracorporeal life support, extracorporeal membrane oxygenation or other circulatory support techniques. It was reported that the survival of patients was negatively influenced the longer erythrocyte concentrates were stored at 4 °C prior to transfusion, for example, after heart surgery6,7. However, the studies that reached this conclusion, especially the retrospective one6, were intensely criticised and some other retrospective and prospective studies were not able to show significant differences in outcomes (multiple organ dysfunction score, decrease of 90-day mortality) following transfusion of fresh or older blood8,9. Nevertheless, less pronounced effects cannot be excluded. Red cell concentrates seem to be stable to some extent during storage at 4 °C, since the rate of haemolysis is normally below 1% before transfusion. This is, however, obviously only a semi-stable condition, since with increasing storage times, an average of 25% of transfused erythrocytes may disappear from the circulation10. The very considerable temperature increase from 4 °C to 37 °C and the mechanical stress during circulation in the patient are great challenges to transfused erythrocytes. These effects may be even more pronounced if the patient needs extracorporeal circulation, because of the huge area of artificial surfaces and mechanical damage from blood pumps11. The influence of artificial surfaces on corpuscular blood components as well as the activation or inhibition of different haemostatic parameters can be investigated effectively in a closed system, such as the model of extracorporeal circulation used in our study. One advantage of using such a model is that the patient’s autogenic regulation, which may attempt to equalise the effects caused by extracorporeal circulation, can be excluded. The aim of this study was to investigate the influence of extracorporeal circulation on various parameters of erythrocytes that had been stored at 4 °C for different periods of time (6, 20, and 34 days after blood donation), using a HLM model at 37 °C. Samples were taken at the beginning and after 2, 4 and 6 hours of circulation. The most significant change observed was a rapid increase in methaemoglobin (MetHb) concentration during circulation. Since the formation of MetHb is associated with the generation of reactive oxygen species (ROS), we further investigated whether the inclusion of suitable antioxidant substances could initially inhibit lipid peroxidation in a model system using erythrocyte ghosts.
Front Cover: Ultraviolet radiation oxidative stress affects eye health (J. Biophotonics 7/2018)
2018-07-01

The role of ultraviolet radiation in oxidative stress‐related ocular pathologies is less known than its role in skin cancer. Excessive exposure to ultraviolet radiation is associated with increased oxidative stress in eye tissues, which may promote the development of photokeratitis, cataract, and retinal damages. Children are especially vulnerable: large pupils, transparent ocular media. Efficient everyday protection of the eye should be considered from early age. (Image: with permission from Carl Zeiss Vision International GmbH, Aalen, Germany) Further details can be found in the article by Iliya V. Ivanov, Timo Mappes, Patrick Schaupp, et al. ( e201700377 ). image
Determination of the neutrino mass in 163 Ho
2018-07-01

KATRIN plans to determine the electron anti-neutrino mass in the Tritium decay. Electron capture in 163Ho can measure the electron neutrino mass supported by the small decay energy The decay energy of 2.8 keV is used to emit a neutrino and to excite the Dy atom. The neutrino mass is then given by the difference between the Q value and the upper end of the Dy deexcitation spectrum. The Dirac-Hartree-Fock approach is used for the bound and the continuum states in Holmium and in Dysprosium. The present background must be reduced by at least two orders to extract the neutrino mass from the spectrum. The present work discuses the one- and the two-hole excitations in Dy. The two-hole states are excited by shake-up of an electron into a free bound state and the shake-off into the continuum. The shake-off contribution can practically be neglected. It seems not to influence the neutrino mass determination.
Abstract LB-177: Quantification of cell signaling proteins by immuno-MALDI
2018-07-01

Abstract Introduction. To improve cancer patient stratification and overcome the drawbacks of currently used approaches to assess signaling pathway proteins, we set out to develop immuno-matrix assisted laser ionization/desorption (iMALDI) assays combined with a phosphatase-based phosphopeptide quantitation (PPQ) approach to measure PI3K/AKT/mTOR pathway activity. Specifically, we targeted the C-terminal tryptic peptides of AKT1 and AKT2 due to their involvement in full kinase activation. Methods. Following trypsin digestion of cell lysate, stable isotope-labeled standard (SIS) peptides are added. After splitting the solution, one aliquot is treated with phosphatase. Bead-coupled antibodies enrich the non-phosphorylated target peptides, which are washed and spotted onto a MALDI plate, and acidic MALDI matrix elutes the peptides. The resulting light/heavy ratios of both aliquots allow the calculation of protein expression levels and peptide phosphorylation stoichiometry. Results. The iMALDI assays were validated for linear range and accuracy, as well as interference screening, requiring only ~50 μg of total cell or tissue lysate protein to quantify both AKT1 and AKT2 expression levels and phosphorylation stoichiometry. CVs of technical replicates were found to consistently be below 10%. We were able to quantify AKT1 and AKT2 from various cell lines and fresh frozen tumor samples, including SW480 and HCT116 colon cancer cell lines, MDA-MB-231 breast cancer cells, and colon cancer and breast cancer tumor lysates. Further, a direct comparison of matched fresh frozen and formalin-fixed paraffin-embedded (FFPE) tissues showed that the expression levels and phosphorylation stoichiometry quantified differ depending on the tissue preservation method, and that phosphorylation stoichiometries above 30% occur in only a small subset of samples. A direct comparison of four pairs of normal and adjacent tumor tissues showed elevated AKT1 phosphorylation stoichiometry of ~40% in a colorectal cancer liver metastasis, and significantly elevated AKT1 (3.6-fold) and AKT2 (2.2-fold) expression levels in a surgical breast tumor sample. Future directions. In a next step, patient-derived mouse xenograft tissue samples, collected after specific drug treatment, will be analyzed, and the AKT results will be correlated to genomic data to answer the hypothesis whether the AKT expression levels and phosphorylation stoichiometries correlate with response to treatment. Citation Format: Robert Popp, René P. Zahedi, André LeBlanc, Yassene Mohammed, Adriana Aguilar-Mahecha, Oliver Pötz, Mark Basik, Gerald Batist, Christoph H. Borchers. Quantification of cell signaling proteins by immuno-MALDI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-177.
Theology's munus triplex? Reconsidering Theology's Relationship to the Sciences
2018-07-01

Abstract Despite the complicated history of exchange between theology and science, the relation between the two can perhaps be summarized succinctly by Ian Barbour's influential taxonomy: conflict, independence, dialogue or integration. This article explores an alternative route by demonstrating how three recent theologians (Barth, Van Huyssteen and Webster) offer recognizably distinct visions for Christian theology's interdisciplinary encounters which can be characterized respectively as prophetic, priestly and royal. A second section of this article discusses the fruitfulness of adopting a munus triplex approach to the interdisciplinary question, as well as anticipating potential objections to transferring the ‘offices’ of Christ to the task of theology.
P1‐116: NEUROFILAMENT LIGHT LEVELS IN THE CEREBROSPINAL FLUID ARE UNCOUPLED OF AMYLOIDOSIS IN LATE STAGE PATHOGENESIS OF APP TRANSGENIC MICE
2018-07-01

The β-site amyloid precursor protein-cleaving enzyme (BACE1) constitutes a major target for the potential treatment of Alzheimer's disease. Previous studies have shown, that long-term inhibition of BACE1 not only prevents amyloid-beta (Aβ) production and deposition but also suppresses the neurofilament light chain (NfL) increase in the cerebrospinal fluid (CSF) of amyloid precursor protein (APP) transgenic mice during the initial phase of cerebral β-amyloidosis (Bacioglu et al., Neuron 2016). CSF NfL is assumed to be a promising biomarker for neurodegeneration. However, it is not known whether BACE inhibition can also block the CSF NfL increase in APP transgenic mice at a later stage of amyloid pathology. APPPS1 transgenic mice (Radde et al., EMBO Rep 2006) were treated with a potent BACE1 inhibitor for 3 months at an early, intermediate or late stage of Aβ deposition (1.5, 12, or 18 months, respectively). After the treatment, brain Aβ and CSF NfL levels were assessed using stereological quantification and sandwich immunoassays. Measurements were compared to non-treated littermates and baseline controls. BACE1 inhibitor treatment at 1.5 months of age largely prevented Aβ deposition and concomitantly suppressed the CSF NfL increase. Treatment at an intermediate stage similarly prevented both brain Aβ and CSF NfL increase. In aged transgenic mice, i.e. at the plateau phase of Aβ deposition, BACE1 treatment was able to reduce brain Aβ below baseline but CSF NfL increased. Results demonstrate that CSF NfL levels are tightly connected to β-amyloidosis at early stages of pathogenesis but become independent from Aβ increase at late stages of β-amyloidosis. These observations suggest that Aβ aggregation triggers a neurodegenerative process that at later time points, when Aβ deposition reaches a plateau, becomes independent from Aβ increase. These findings imply that BACE1 inhibitors in clinical trials are most effective in AD patients with low or moderate Aβ burden and become arguably less valid in a more progressed phase of the disease.
P3‐289: HARMONIZATION OF SCD OPERATIONALIZATION ACROSS DIFFERENT MEMORY CLINIC SETTINGS: THE EURO‐SCD STUDY
2018-07-01

Subjective cognitive decline (SCD) may serve as a condition for early identification of Alzheimer's disease (AD) and defines potential target populations for AD prevention trials. Due to the variability in operationalization, however, the enrichment rate for preclinical AD in SCD samples is different between studies and recruitment sites. The JPND-program EURO-SCD aims at harmonizing SCD assessment across memory clinics in different countries. In the first part of the study, existing SCD samples from three sources (German DELCODE study, Amsterdam dementia cohort, IDIBAPS Barcelona) were compared with regard to CSF-biomarker-based AD pathology. CSF biomarkers were centrally measured. The predictors of differences in the frequency of AD pathology between the three sources were determined. In the second part of the study, SCD patients were collected prospectively with a harmonized protocol across sites. The frequency of AD pathology was determined with FBB-PET and compared across two sources (DELCODE, Amsterdam dementia cohort). The comparison of the retrospectively analyzed SCD samples (DELCODE: n=44; Amsterdam, m=50, Barcelona, n=44) revealed differences in the rate of amyloid pathology between 28% and 50%. There was also variation in Tau and pTau pathology as well as in the ratio Aß42/Tau. Predictor of pathology were mainly age and the APOE-genotype. Additional predictors were levels of IADL impairment and in the case of Aß42/Tau center effects, which could not be explained further. In the prospective part 31 SCD patients in Amsterdam and 59 patients in DELCODE were recruited with a harmonized SCD protocol and received FBB-PET. The rates of amyloid positivity and the comparability across sources will be reported in the presentation. Harmonization of SCD operationalization is crucial for multicenter studies in this group of patients, which are particularly promising for early treatment and prevention studies. The EURO SCD study is the first initiative for harmonized SCD recruitment across different countries and will provide valuable information on the predictors of AD pathology in SCD.
F4‐07‐03: RELATIONSHIP BETWEEN LOCUS COERULEUS MRI CONTRAST, COGNITION AND CSF BIOMARKERS IN AGING AND ALZHEIMER'S DISEASE
2018-07-01

The occurrence of abnormal tau in the locus coeruleus (LC) may be a critical early step in the pathogenesis of Alzheimer's disease (AD). The high content of neuromelanin in the LC serves as an endogenous contrast agent for magnetic resonance imaging (MRI) providing a unique opportunity to assess the integrity of the LC in vivo. We recently demonstrated T1-weighted Fast Low Angle Shot (FLASH) imaging could be used to visualize and quantify LC signal intensity changes in young and older adults. Here we compared LC signal intensity changes in subjective cognitive complainers (SCD), individuals with mild cognitive impairment (MCI) and AD patients to age-matched controls and assessed how LC signal intensity relates to cognitive and cerebrospinal fluid (CSF) biomarkers of AD. Baseline data from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study comprising healthy elderly adults (n=59), SCD (n=19), MCI (n=10) and subjects with AD (n=6) were analysed. All subjects were scanned at 3T using a 3D T1-weighted FLASH sequence (0.75mm isotropic resolution whole brain acquisition). FLASH images were sinc interpolated and upsampled to 0.375mm3 resolution prior to manual segmentation of the LC. Median and maximum LC signal intensity was assessed relative to reference regions delineated in the rostral pontomesencephalic area. We found no significant difference in median or maximum LC signal intensity between groups. Linear regression analyses across groups (n=94) revealed median (r= -.42, p< 0.0005) and maximum LC signal intensity (r= -.40, p= 0.001) negatively correlated with the Wechsler Memory Scale (WMS-R) forward digit span test. In a smaller subset of individuals with CSF biomarkers (n=30), we found a significant negative correlation between LC max signal intensity, Aβ42/40 (r= -.50, p< 0.005) and Aβ42/phospho-tau (r= -.51, p<0.004). However no relationship between LC signal intensity and CSF phospho-tau or total tau was observed. Whilst no significant difference in LC signal intensity was observed between groups, individuals with elevated LC signal intensity in AD demonstrated impaired working memory. The significant negative relationship between LC signal intensity and CSF amyloid also suggests changes in LC neuromelanin identified using T1-weighted FLASH imaging at 3 T may relate to AD pathology.
P2‐447: MICROSTRUCTURAL CHANGES IN ALZHEIMER'S DISEASE, MILD COGNITIVE IMPAIRMENT, AND SUBJECTIVE COGNITIVE DECLINE BASED ON MULTICENTER DIFFUSION TENSOR IMAGING: A TBSS ANALYSIS OF DELCODE DATA
2018-07-01

Fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MO) are diffusion tensor imaging (DTI) parameters shown to provide valuable information on microstructural neuronal integrity and may serve as early diagnostic markers of Alzheimer's disease (AD). Subjective cognitive decline (SCD), an at risk stage of AD, is still poorly studied with respect to microstructural brain changes. In this study, we present first results from a multicenter DTI study using tract-based spatial statistics. We investigated FA, MD and MO in a multicentric sample of 172 participants consisting of individuals with AD, mild cognitive impairment (MCI), and SCD who were recruited in the DELCODE study, a prospective longitudinal observational study. DTI data were acquired at six sites, using homogeneous scanning parameters and protocols. We performed tract-based spatial statistics to determine alterations of FA, MD and MO in the white matter (WM). In comparison to the control group, FA in the SCD group was significantly decreased in the right inferior fronto-occipital fasciculus (IFOF), bilateral corticospinal tract, bilateral internal capsule (posterior limb), and right anterior thalamic radiation (ATR; p < .05, corrected for multiple comparisons). Moreover, significant increases in MO for the AD group relative to controls was found in right IFOF and ATR. While no effect of MD emerged, trends of decreased MO in all groups compared to controls were detected in various WM regions, including the body and splenium of the corpus callosum, left anterior limb of the external capsule, as well as cingulum.
F1‐04‐02: ASSOCIATION BETWEEN NEURAL NOVELTY RESPONSES AND CSF BIOMARKERS OF ALZHEIMER'S DISEASE: ANATOMICAL SPECIFICITY AND DEPENDENCE ON ATROPHY
2018-07-01

The impact of tau- and amyloid pathology on memory function in preclinical Alzheimer disease (AD) is still poorly understood. Both pathologies may have anatomically specific effects on memory function that are independent of local structural integrity. We conducted a cross-sectional analysis of the longitudinal observational DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study which enrols participants classified as healthy (cognitively unimpaired), subjective cognitive decline (SCD), mild cognitive impairment (MCI) and mild Alzheimer's dementia. As part of the DELCODE MRI protocol, participants incidentally encoded novel and familiar photographs depicting indoor or outdoor scenes in a task fMRI session. Of the first 394 participants, 80 participants were available with both task-fMRI and CSF levels of total-tau and Aß-42 (39 healthy, 20 SCDs, 15 MCIs, 6 Alzheimer's dementia). Across the entire group, novel scenes were associated with higher fMRI BOLD responses across many brain regions, including, medial temporal, parietal, visual and frontal regions. In the HC/SCD/MCI group, higher CSF total tau levels were specifically associated with lower novelty responses in the right amygdala and right hippocampus and this association was independent of CSF Aß42 levels, DELCODE site, age or gender. A mediation analysis showed that hippocampal or amygdala volume did not mediate the relationship between tau-levels and novelty responses. In the MCI/AD group, lower Aß42 levels were specifically associated with lower novelty responses in the precuneus and this association was independent of CSF t-tau levels, DELCODE site, age and gender. A mediation analysis showed that precuneus volume did not mediate the relationship between Aß-42 levels and novelty responses These results indicate that CSF indices of tau and amyloid pathology are associated with independent and anatomically specific functional reductions in memory processing. The anatomical specificity is compatible with the predilection areas of tau- and amyloid pathology as known from molecular imaging studies and post mortem histology. These associations remain robust after considering the structural integrity of the same brain region and hence indicate that both pathologies cause synaptic dysfunction independent of neurodegeneration. The independent functional impact of tau- and amyloid pathology shows their additive interaction is not necessary to cause neuronal dysfunction.
P2‐431: RELATIONSHIP BETWEEN LOCAL RESTING STATE ACTIVITY, β‐AMYLOID DEPOSITION AND MEMORY PERFORMANCE IN THE DZNE: LONGITUDINAL COGNITIVE IMPAIRMENT AND DEMENTIA STUDY (DELCODE)
2018-07-01

Recent multicenter studies provide rich insights in restingstate alterations, while different scanning protocols between sites sometimes lower interpretability (Teipel et al., 2017a, 2017b). The fractional amplitude of low frequency fluctuations (fALFF) is a local restingstate measure with good clinical applicability (Zou et al., 2008). As little is known about changes in fALFF during the development of Alzheimer's disease (AD) and their relationship to amyloid load or memory performance, this question was assessed using data from the first release of the DZNE - Longitudinal Cognitive Impairment and Dementia Study (DELCODE) making use of standardized MR-protocols including healthy elderly subjects (HC), patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and AD. Baseline data of 365 subjects from the first release of the DELCODE study were included in the analysis. All subjects completed an eyes-closed restingstate scan as part of a general scanning protocol. Preprocessing of the restingstate fMRI data was carried out using DPARSF (Yan, 2010), SPM8 and REST (Song et al., 2011). fALFF was calculated on whole brain level and compared between groups. Simple regression analysis was used to compare fALFF with subjects’ Aß40/Aß42-ratio and memory performance (assessed by the ADAS-Cog (Rosen et al., 1984)). We found a main effect of diagnosis on fALFF in the bilateral hippocampus, posterior cingulate, dorsal anterior cingulate cortex and anterior insula. While a gradual decrease in fALFF in the salience and default-mode network was found over the diagnostic stages towards the development of AD, a gradual increase was found in fALFF in the hippocampus. A direct correlation was found between the Aß40/Aß42-ratio and fALFF in the precuneus and the entorhinal cortex. Memory performance showed a linear correlation with fALFF in the precuneus. We identified gradual changes in restingstate activity between the different stages over the development of AD, correlating with amyloid load and memory performance. Complementing previous studies (Teipel et al., 2017a,b), those results might be useful to define early markers of disease progression, that might serve as biomarkers on longitudinal level.