Torsion-balance tests of the weak equivalence principle

We briefly summarize motivations for testing the weak equivalence principle and then review recent torsion-balance results that compare the differential accelerations of beryllium-aluminum and beryllium-titanium test body pairs with precisions at the part in $10^{13}$ level. We discuss some implications of these results for the gravitational properties of antimatter and dark matter, and speculate about the prospects for further improvements in experimental sensitivity.Comment: 17 pages, 9 figures (in press Classical Quantum Gravity 2012

The associations between serum brain-derived neurotrophic factor, potential confounders, and cognitive decline: A longitudinal study

Brain-derived neurotrophic factor (BDNF) plays a role in the maintenance and function of neurons. Although persons with Alzheimer's disease have lower cortical levels of BDNF, evidence regarding the association between circulating BDNF and cognitive function is conflicting. We sought to determine the correlates of BDNF level and whether BDNF level was prospectively associated with cognitive decline in healthy older adults. We measured serum BDNF near baseline in 912 individuals. Cognitive status was assessed repeatedly with the modified Mini-Mental Status Examination and the Digit Symbol Substitution test over the next 10 years. We evaluated the association between BDNF and cognitive decline with longitudinal models. We also assessed the association between BDNF level and demographics, comorbidities and health behaviors. We found an association between serum BDNF and several characteristics that are also associated with dementia (race and depression), suggesting that future studies should control for these potential confounders. We did not find evidence of a longitudinal association between serum BDNF and subsequent cognitive test trajectories in older adults, although we did identify a potential trend toward a cross-sectional association. Our results suggest that serum BDNF may have limited utility as a biomarker of prospective cognitive decline

Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor and Cognitive Function in Non-Demented Subjects

Brain-derived neurotrophic factor (BDNF) is an activity-dependent secreted protein that is critical to organization of neuronal networks and synaptic plasticity, especially in the hippocampus. We tested hypothesis that reduced CSF BDNF is associated with age-related cognitive decline.CSF concentration of BDNF, Abeta(42) and total tau were measured in 128 cognitively normal adults (Normals), 21 patients with Alzheimer's disease (AD), and nine patients with Mild Cognitive Impairment. Apolipoprotein E and BDNF SNP rs6265 genotype were determined. Neuropsychological tests were performed at baseline for all subjects and at follow-up visits in 50 Normals. CSF BDNF level was lower in AD patients compared to age-matched Normals (p = 0.02). CSF BDNF concentration decreased with age among Normals and was higher in women than men (both p<0.001). After adjusting for age, gender, education, CSF Abeta(42) and total tau, and APOE and BDNF genotypes, lower CSF BDNF concentration was associated poorer immediate and delayed recall at baseline (both p<0.05) and in follow up of approximately 3 years duration (both p<0.01).Reduced CSF BDNF was associated with age-related cognitive decline, suggesting a potential mechanism that may contribute in part to cognitive decline in older individuals

Distinct degassing pulses during magma invasion in the stratified Karoo Basin – New insights from hydrothermal fluid flow modelling

Magma emplacement in organic‐rich sedimentary basins is a main driver of past environmental crises. Using a 2D numerical model, we investigate the process of thermal cracking in contact aureoles of cooling sills and subsequent transport and emission of thermogenic methane by hydrothermal fluids. Our model includes a Mohr‐Coulomb failure criterion to initiate hydrofracturing and a dynamic porosity/permeability. We investigate the Karoo Basin, taking into account host‐rock material properties from borehole data, realistic total organic carbon content, and different sill geometries. Consistent with geological observations, we find that thermal plumes quickly rise at the edges of saucer‐shaped sills, guided along vertically fractured high permeability pathways. Contrastingly, less focused and slower plumes rise from the edges and the central part of flat‐lying sills. Using a novel upscaling method based on sill‐to‐sediment ratio we find that degassing of the Karoo Basin occurred in two distinct phases during magma invasion. Rapid degassing triggered by sills emplaced within the top 1.5 km emitted ~1.6·103 Gt of thermogenic methane, while thermal plumes originating from deeper sills, carrying a 12‐times greater mass of methane, may not reach the surface. We suggest that these large quantities of methane could be re‐mobilized by the heat provided by neighboring sills. We conclude that the Karoo LIP may have emitted as much as ~22.3·103 Gt of thermogenic methane in the half million years of magmatic activity, with emissions up to 3 Gt/year. This quantity of methane and the emission rates can explain the negative δ13C excursion of the Toarcian environmental crisis. Key Points Sill geometry and emplacement depth as well as intruded host rock type are the main factors controlling methane mobilization and degassing Dehydration‐related porosity increase and pore‐pressure‐induced hydrofracturing are important mechanisms for a quick transport of methane from sill to the surface The Karoo Basin may have degassed ~22.3·103 Gt of thermogenic methane in the half million years of magmatic activit

Adipocytokines and CD34+ Progenitor Cells in Alzheimer's Disease

BACKGROUND: Alzheimer's disease (AD) and atherosclerosis share common vascular risk factors such as arterial hypertension and hypercholesterolemia. Adipocytokines and CD34(+) progenitor cells are associated with the progression and prognosis of atherosclerotic diseases. Their role in AD is not adequately elucidated. METHODS AND FINDINGS: In the present study, we measured in 41 patients with early AD and 37 age- and weight-matched healthy controls blood concentrations of adiponectin and leptin by enzyme linked immunoabsorbent assay and of CD34(+) progenitor cells using flow cytometry. We found significantly lower plasma levels of leptin in AD patients compared with the controls, whereas plasma levels of adiponectin did not show any significant differences (AD vs. control (mean ± SD): leptin:8.9 ± 5.6 ng/mL vs.16.3 ± 15.5 ng/mL;P = 0.038; adiponectin:18.5 ± 18.1 µg/mL vs.16.7 ± 8.9 µg/mL;P = 0.641). In contrast, circulating CD34(+) cells were significantly upregulated in AD patients (mean absolute cell count ± SD:253 ± 51 vs. 203 ± 37; P = 0.02) and showed an inverse correlation with plasma levels of leptin (r =  -0.248; P = 0.037). In logistic regression analysis, decreased leptin concentration (P = 0.021) and increased number of CD34(+) cells (P = 0.036) were both significantly associated with the presence of AD. According to multifactorial analysis of covariance, leptin serum levels were a significant independent predictor for the number of CD34(+) cells (P = 0.002). CONCLUSIONS: Our findings suggest that low plasma levels of leptin and increased numbers of CD34(+) progenitor cells are both associated with AD. In addition, the results of our study provide first evidence that increased leptin plasma levels are associated with a reduced number of CD34(+) progenitor cells in AD patients. These findings point towards a combined involvement of leptin and CD34(+) progenitor cells in the pathogenesis of AD. Thus, plasma levels of leptin and circulating CD34(+) progenitor cells could represent an important molecular link between atherosclerotic diseases and AD. Further studies should clarify the pathophysiological role of both adipocytokines and progenitor cells in AD and possible diagnostic and therapeutic applications

Metabolite Profiling of Alzheimer's Disease Cerebrospinal Fluid

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine

Body Fluid Cytokine Levels in Mild Cognitive Impairment and Alzheimer’s Disease: a Comparative Overview

This article gives a comprehensive overview of cytokine and other inflammation associated protein levels in plasma, serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). We reviewed 118 research articles published between 1989 and 2013 to compare the reported levels of 66 cytokines and other proteins related to regulation and signaling in inflammation in the blood or CSF obtained from MCI and AD patients. Several cytokines are evidently regulated in (neuro-) inflammatory processes associated with neurodegenerative disorders. Others do not display changes in the blood or CSF during disease progression. However, many reports on cytokine levels in MCI or AD are controversial or inconclusive, particularly those which provide data on frequently investigated cytokines like tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6). The levels of several cytokines are possible indicators of neuroinflammation in AD. Some of them might increase steadily during disease progression or temporarily at the time of MCI to AD conversion. Furthermore, elevated body fluid cytokine levels may correlate with an increased risk of conversion from MCI to AD. Yet, research results are conflicting. To overcome interindividual variances and to obtain a more definite description of cytokine regulation and function in neurodegeneration, a high degree of methodical standardization and patients collective characterization, together with longitudinal sampling over years is essential