julilili42/papers huggingface dataset:
Physical Activity and Affective Well-Being in Everyday Life
2016-07-01

Abstract. Multiple studies verified the acute positive effects of physical activity on affective well-being, focusing on sport activities in laboratory settings or supervised programs. This study builds on existing ambulatory assessment studies that indicate positive associations between physical activity and affective well-being (valence, energetic arousal) in everyday life and explicitly differentiates between sport activities and daily physical activities. Moreover, the sustainability of effects is explored. For 7 days, 21 men and 25 women (M age = 32 years) participated in the study. Physical activity was captured objectively by an accelerometer and additionally with an activity diary. Affective well-being was gathered via a smartphone multiple times per day. Multilevel analyses revealed positive effects on affective well-being (valence, calmness, energetic arousal) for sport activities included in the daily routine. Daily physical activity showed acute positive effects for valence and energetic arousal but not for calmness. However, at the day’s end, sport activities and daily physical activity were positively associated with valence and calmness. This study gives further background knowledge for activity recommendations based on the affect-regulating potential of physical activity.
O2‐03‐02: are White Matter Hyperintensities a Core Feature of Alzheimer’s Disease or Just a Reflection of Amyloid Angiopathy? Evidence From the Dominantly Inherited Alzheimer Network (DIAN)
2016-07-01

We previously established that white matter hyperintensities (WMH) volume is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD) up to 20 years prior to expected symptom onset. One potential explanation is that WMH are, in part, a reflection of cerebral amyloid angiopathy (CAA). We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between mutation status and WMH in individuals from DIAN. The study comprised participants (n=175, mean age=41.05, 57% women) from DIAN, including 112(64%) with a mutation that results in AD and 63(36%) first-degree relatives who were non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent’s symptom onset age from the participant’s age. Baseline MRI data were analyzed for WMH volume and for cerebral microbleeds, a radiological marker of CAA. We examined WMH differences between carriers and non-carriers with respect to EYO, differences between carriers and non-carriers in presence of microbleeds, and tested whether the association between WMH and mutation status is dependent on the presence of microbleeds. Mutation carriers were more likely to have a microbleed than non-carriers(20% vs. 6%, p<0.05) and individuals with microbleeds had higher WMH volume than those without(p<0.05). Total WMH volume was increased in mutation carriers up to 20 years prior to EYO, after controlling for microbleed status. Total WMH also remained elevated in mutation carriers even after exclusion of individuals with microbleeds. Mediations tests demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds(p=0.03) but a significant direct effect of WMH remained (p=0.02) after controlling for presence of microbleeds. Although there is some co-dependency between WMH and cerebral microbleeds, the observed increases in WMH among mutation carriers is not fully mediated by this marker of cerebral amyloid angiopathy. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.
AVDTC of generalized 3-Halin graphs
2016-07-01

In this paper, we prove that the adjacent vertex distinguishing total chromatic number of a generalized Halin graph with maximum degree 3 is 5. This result answers an open question of Chen and Zhang [11].
F5‐02‐03: BDNF VAL66MET Moderates Cognitive Impairment, Neuronal Dysfunction and TAU in Preclinical Autosomal Dominant Alzheimer's Disease
2016-07-01

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate Aβ-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease (AD). However, the effect of BDNF in autosomal dominant AD (ADAD) is unknown. We investigated the effect of BDNF Val66Met on cognitive function, glucose metabolism, tau and Aβ in preclinical ADAD. As the apolipoprotein E (APOE) ε4 allele has also previously been shown to interact with BDNF in sporadic AD, we also explored for similar interaction of ɛ4 in ADAD. Baseline clinical, neuropsychological, genetic, biomarker and neuroimaging data from the Dominantly Inherited Alzheimer Network (DIAN) were analyzed in 131 mutation non-carriers (NC) and 143 preclinical ADAD mutation carriers (MC), an average 12 years prior to clinical symptom onset. BDNF genotype data were obtained for MCs (95 Val66 homozygotes, 48 Met66 carriers). Among preclinical MCs, Met66 carriers had worse memory performance, lower glucose metabolism and increased levels of cerebrospinal fluid (CSF) tau and phosphorylated tau (p-tau181) when compared to Val66 homozygotes (Figure 1). Cortical Aβ and CSF Aβ42 levels did not significantly differ between preclinical MC Val66 homozygotes and Met66 carriers (Figure 1). There was an effect of APOE on Aβ levels but not cognitive function, glucose metabolism or tau. There were no significant interactions between APOE and BDNF on any biomarker or cognitive outcome measure. Magnitude of abnormality in episodic memory performance, and markers of Aβ, phosphorylated tau and glucose metabolism in preclinical MC Val66 homozygotes and preclinical MC Met66 carriers when compared to mutation non-carriers (error bars represent 95% confidence intervals). As in sporadic AD, the deleterious effects of Aβ on cognitive function, glucose metabolism and tau in preclinical ADAD mutation carriers are less in Val66 homozygotes. The results suggest that allelic variation in BDNF and APOE may affect different AD processes with ε4 increasing cortical Aβ accumulation and Met66 moderating cognitive impairment and neuronal dysfunction through tau. To date, this is the only genetic factor found to moderate downstream effects of Aβ in ADAD, and has implications for clinical trial designs.
Flexible in-silicon checking of run-time programmable assertions
2016-07-01

Recently, Assertion-Based Verification (ABV) has been significantly improved and used not only in academia but also in industry. In this paper, we present a new assertion checking approach that dynamically interprets a software-defined assertion checker during run-time. In contrast to the state-of-the-art hardware checker, the presented method compiles its checker to instructions, which can be changed flexibly by software in the in-silicon phase. A stand-alone hardware block, called assertion processing unit (APU), is used for implementing the compiled instructions. This unit handles the storage of the checker code, the execution of the checking, and the feedback of checked results in the system run-time environment. We have successfully evaluated this approach on an FPGA-based prototyping board, showing measurable benefits of this approach.
O5‐02‐02: Personality Characteristics and Alterations in Familial Alzheimer's Disease in the Dominantly Inherited Alzheimer Network (DIAN)
2016-07-01

Specific personality traits have been described in dementia of the Alzheimer type. In this study we sought to characterize personality features in carriers of autosomal dominant Alzheimer's disease (ADAD) mutations, before and after the onset of the disease. We examined self- and informant-report personality ratings for 155 participants enrolled in the Dominantly Inherited Alzheimer Network (DIAN) who had at least two study visits. The International Personality Item Pool (IPIP) was used to assess personality on five broad dimensions: openness, agreeableness, conscientiousness, extraversion, and neuroticism. The participants were divided into three groups based on mutation status and Clinical Dementia Rating Scale (CDR) score at first and last visits: non-carriers (NCs; n=46), mutation carriers (MCs) with CDR=0 at both visits (presymptomatic MCs; n=41), MCs with CDR≥0.5 at both visits (symptomatic MCs; n=68). For each personality dimension, the three groups were compared on baseline ratings and change between first visit and last visit, using mixed-effects models. Participant ratings and informant ratings were examined separately. At baseline, presymptomatic MCs rated themselves similarly to NCs on all personality domains; however, informants rated presymptomatic MCs lower on conscientiousness (p<0.05) and higher on neuroticism (p<0.01) than NCs. Symptomatic MCs rated themselves lower on conscientiousness (p<0.0001), lower on extraversion (p<0.001), and higher than neuroticism (p<0.01) than NCs; informants rated symptomatic MCs lower on openness (p<0.01), agreeableness (p<0.01), conscientiousness (p<0.0001) and extraversion (p<0.0001), and higher on neuroticism (p<0.0001) than NCs. NCs had no change in personality ratings between first visit and last visit, regardless of rating party. Presymptomatic MCs rated themselves similarly at first visit and last visit; however, they were rated by informants to be less open at last visit than first visit (p<0.05). Symptomatic MCs rated themselves to be less open at the last visit than the first visit (p<0.05); informants rated symptomatic MCs to be less open (p<0.01) and less conscientious (p<0.05) at the last visit than the first visit. There were evident personality changes with the progression of AD pathology. Self- and informant-ratings started to diverge at disease onset. ADAD mutation carriers may possess some life-long traits characterized by lower conscientiousness and higher neuroticism.
Linear and non-linear optical properties of plasmonic nano-antennas
2016-07-01

Plasmonics is now well established field finding numerous applications in pharmacology, biology, optoelectronics and metamaterials among others. Linear optical properties and plasmon resonances of metallic nanoparticles or nano-antennas are well described in the literature by extinction and/or scattering spectroscopies and by radiation patterns in direct or in Fourier space. However, much less is known on their non-linear optical properties, and in the role of plasmon resonances in the enhancement of these effects. Two-photon luminescence (TPL) and second harmonic generation (SHG) both are prominent examples of non-linear effects observed on metallic nanoparticles. We propose in this paper to discuss both linear and non-linear optical properties of original single homogeneous and heterogeneous nano-antennas consisting in particle heterodimers of Au/Au, Au/Ag and Au/Al compositions [1].
P3‐246: Influence of the Retrieval Frequency on the Memory Performance in Elderly Healthy Subjects and Patients with Alzheimer's Disease
2016-07-01

There is controversial discussion regarding the influence of retrieval frequency or remoteness of an event on the memory performance and their dependence on the neurodegenerative processes in Alzheimer's disease (AD). Regarding this issue we conducted several studies with neuropsychological and imaging methods in terms of memory performance in autobiographical and historical events. In healthy controls (HC) and AD patients, we examined the recall performance of historical events, depending on the remoteness to the event or its retrieval frequency. The ranking of the retrieval frequency was operationalized through a paired comparison of all events. Furthermore, we investigated in HC subjects and patients with AD the memory performance of autobiographical events depending on the remoteness of the event or its retrieval frequency. With functional magnetic resonance imaging, we then examined in HC subjects and patients with AD the influence of the remoteness to the event or its retrieval frequency on brain activity. In a fourth study, we correlated the dependence of the retrieval frequency for the memory of historical events with the hippocampal degeneration in HC subjects and patients with AD using voxel-based morphometry. The behavioral data showed that as well in the HC as in the AD groups the memory performance for historical and autobiographical events depended on the retrieval frequency. The memory was accompanied by bilateral activation in the hippocampus, medial temporal lobe, angular gyrus, precuneus and medial prefrontal regions. The activation in this network was reduced in patients with AD, whereas in HC and AD subjects activity in the hippocampus increased with the retrieval frequency. In contrast to rarely retrieved events the memory performance for frequently accessed events was independent of the degree of atrophy of the hippocampus. In summary, our studies have shown that the memory performance for historical and autobiographical events depends on retrieval frequency and this is associated with an increase in brain activity in the hippocampus. Moreover, the memory performance of frequently retrieved events appears to be less affected by the atrophy of the hippocampus in AD, either by compensatory hyperactivity in this region of the brain, or by additional activity in other brain regions.
P4‐145: Decreased Body Mass Index in the Preclinical Stage of Alzheimer's Disease: Evidence From the Dominantly Inherited Alzheimer Network
2016-07-01

In preclinical Alzheimeŕs disease (AD) the exact time course of body-mass index (BMI) changes and their relation with cerebral amyloid load and episodic memory are still unclear. We analyzed cross-sectional data from 230 asymptomatic members of families with autosomal dominant AD (ADAD) participating in the Dominantly Inherited Alzheimer Network (DIAN) study. The relationship between BMI and AD-related biomarkers, clinical and psychometric parameters as a function of estimated years to symptom onset (EYO) was examined. Preclinical mutation carriers showed significantly lower BMIs compared to non-mutation carriers, starting 11.2 years before estimated symptom onset, which was associated with increased global cerebral amyloid load and poorer cognitive performance. Decreasing BMI seems to be part of the preclinical stage of AD. These findings suggest a direct relationship between the pathophysiology of AD and weight control mechanisms and point towards AD as a systemic disease affecting the entire body.
P2‐335: Prevalence of Preclinical Alzheimer's Disease in Patients with Subjective Cognitive Decline: Comparison of Three European Memory Clinic Samples
2016-07-01

Subjective Cognitive Decline (SCD) in cognitively normal elderly individuals has been recognized as a pre-mild cognitive impairment (pre-MCI) at risk state of Alzheimer's disease (AD) and a target population for future AD prevention trials. Currently, however, SCD is heterogeneously defined across studies leading to diverse prevalence of preclinical AD. The aim of the current study was to compare prevalence of preclinical AD in three European memory-clinic based samples of SCD, participating in the European initiative on harmonization of SCD in preclinical AD(Euro-SCD). We compared three memory clinic SCD samples with available CSF data (IDIBAPS, Barcelona, Spain, n=44; VUmc Amsterdam, The Netherlands, n=50; DELCODE multi-center study, Germany, n=44). CSF (Abeta42, Tau, pTau181) was centrally analyzed in VUmc Amsterdam to reduce variability. Biomarker evidenced preclinical AD was defined by abnormal Abeta42 together with either abnormal Tau/or pTau181, and alternatively by abnormal Tau/Abeta42 ratio. Heterogeneity in rates of biomarker abnormality across centers was quantified using Chi2-tests. Logistic regression analysis was used to identify predictors of preclinical AD across the whole sample. Sample descriptions are given in Table 1. Overall, Abeta42 was abnormal in ∼30% of patients. We observed significant heterogeneity between centers in rates of biomarker abnormality for Abeta42 and also heterogeneity in prevalence of preclinical AD when defined by abnormal Abeta42 together with either abnormal Tau/or pTau181. Rates of abnormal Tau/Abeta42 ratio were similar across centers (∼25-30%). Logistic regression analyses showed that age above 65 (OR=9.0, 95%CI: 2.5-33.0), and ApoE4 positivity (OR=13.1, 95%CI: 3.6-47.2) were strongly associated with abnormal Tau/Abeta42 ratio. Across three memory clinic SCD samples, we observed considerably high but also heterogeneous prevalence of abnormal Abeta42 and of a preclinical AD operationalization requiring a combination of abnormal Abeta42 and Tau markers. Differences in the center-specific recruitment protocols, e.g. minimal age inclusion-cutoffs and different criteria to exclude MCI (i.e. in terms of tests, cutoffs and diagnostic algorithms), are potential sources of this variability. These factors should be addressed in the development of a harmonized protocol for SCD case definition. ApoE4 positivity and age above 65 can be used to further enrich homogeneously defined SCD samples for the presence of preclinical AD.
P4‐084: Suppression of TAU Increase in Cerebrospinal Fluid of App Transgenic Mice Provides Evidence for Downstream Effect of Bace1 Inhibition
2016-07-01

The best-validated and established fluid biomarkers for Alzheimer's disease (AD) are reduced Abeta42 and increased tau levels in the cerebrospinal fluid (CSF). We have previously shown that this CSF signature is mirrored in aging Abeta precursor protein (APP) transgenic mice. Despite the lack of neurofibrillary tangles and global neuron loss, they exhibit higher CSF tau concentrations with progressing plaque deposition, indicating that beta-amyloidosis is a major trigger for CSF tau increase. Moreover it suggests that APP transgenic mouse models can be instrumental to predict CSF biomarker changes in clinical trials directed against Abeta. One of the main therapeutic approaches tested for the treatment of AD is the inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). We now used a potent BACE1 inhibitor to treat early-depositing APPPS1 and APP23 mice during six months and evaluated CSF tau changes. For the accurate quantification of murine tau we developed a novel high-sensitivity assay based on the single molecule array (Simoa) technology. In addition, we measured Abeta42 and 40 in the CSF and brain tissue of the same mice and assessed their plaque load by stereological analysis on histological brain sections. As expected, long-term BACE1 inhibition attenuated amyloid deposition in both APP transgenic mouse models. Strikingly, the CSF tau increase, which is normally seen without treatment, was completely abolished. CSF Abeta42 and 40 were reduced compared to baseline levels, which was already evident after one week of BACE1 inhibition. CSF tau concentration however, was unaffected after short-term treatment, accentuating again its link to amyloid plaque load. The prevention of CSF tau increase in two different APP transgenic mouse models suggests that BACE1 inhibition also affects down-stream AD pathologies. The strong correlation between CSF tau and cerebral amyloid renders CSF tau a useful marker for the monitoring of the effectiveness of a BACE1 inhibitor in current clinical trials. S.A.K. and J.S. contributed equally to this work.
P1‐010: Face Name Associative Recognition is Associated with Alzheimer’s Disease Biomarkers in Patients with Subjective Cognitive Decline
2016-07-01

Associative memory is impaired early in the course of Alzheimer's disease (AD). In the ongoing DELCODE (DZNE–Longitudinal Cognitive Impairment and Dementia) study we apply a computerized face-name-associative-recognition test (FNART) to capture putative changes in memory function in patients with Subjective Cognitive Decline (SCD). We hypothesize that FNART performance is associated with AD biomarkers in cerebrospinal fluid (CSF) and discriminates between probands with and without abnormal biomarker status. In this pilot study we analyzed data from 39 memory-clinic patients with SCD (mean age=71.47) who had CSF and neuropsychological data available. Subjects with SCD were referred to memory-clinic because of memory worries and performed within the normal range (1.5 SD) in the CERAD Plus test battery. The following markers of AD pathology in CSF were analyzed centrally with laboratory specific cutoff values: Amyloid ß1-42, phosphorylated-tau, and total-tau. In order to identify SCD patients with a CSF signature indicative of preclinical AD, we calculated an established CSF amyloid/tau ratio score (Hulstaert, 1999). We calculated ROC curves to analyze the discriminatory value of the FNART. For comparison, the Free Recall from the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) was analyzed likewise. In order to examine group differences we applied t-tests for continuous variables. 20-40 % of the SCD subjects had abnormal AD biomarkers, depending on the biomarker examined. Comparing biomarker positive with biomarker negative SCD cases, the FNART revealed differences regarding abnormal tau (p=.021) and an abnormal amyloid/tau ratio (p=.009). The FCSRT free recall score differ in SCD cases with and without biomarker evidence regarding abnormal Aß1-42, which also results in an abnormal amyloid/tau ratio (Table 1). ROC curve analysis revealed that the FNART discriminated between the SCD with and without an abnormal amyloid/tau ratio (AUC=.780). The FCSRT free recall discriminated slightly less (AUC=.679; Table 2). Associative memory is related to AD biomarkers and discriminates SCD patients with a positive biomarker profile. While the data need corroboration with larger samples, they align with results from other studies in suggesting that memory measures might predict AD biomarkers in subjects with SCD and could thus contribute to an enrichment of AD cases in "pre-MCI" samples.
Intestinal barrier analysis by assessment of mucins, tight junctions, and α-defensins in healthy C57BL/6J and BALB/cJ mice
2016-07-02

The intestinal barrier is gaining increasing attention because it is related to intestinal homeostasis and disease. Different parameters have been used in the past to assess intestinal barrier functions in experimental studies; however most of them are poorly defined in healthy mice. Here, we compared a number of barrier markers in healthy mice, established normal values and correlations. In 48 mice (24 C57BL/6J, 24 BALB/cJ background), we measured mucus thickness, and expression of mucin-2, α-defensin-1 and -4, zonula occludens-1, occludin, junctional adhesion molecule-A, claudin-1, 2 and -5. We also analyzed claudin-3 and fatty acid binding protein-2 in urine and plasma, respectively. A higher expression of mucin-2 protein was found in the colon compared to the ileum. In contrast, the α-defensins-1 and -4 were expressed almost exclusively in the ileum. The protein expression of the tight junction molecules claudin-1, occludin and zonula occludens-1 did not differ between colon and ileum, although some differences occurred at the mRNA level. No age- or gender-related differences were found. Differences between C57BL/6J and BALB/cJ mice were found for α-defensin-1 and -4 mRNA expression, and for urine and plasma marker concentrations. The α-defensin-1 mRNA correlated with claudin-5 mRNA, whereas α-defensin-4 mRNA correlated with claudin-3 concentrations in urine. In conclusion, we identified a number of murine intestinal barrier markers requiring tissue analyses or measurable in urine or plasma. We provide normal values for these markers in mice of different genetic background. Such data might be helpful for future animal studies in which the intestinal barrier is of interest.