453 research outputs found
Deformation, seismicity, and fluids: Results of the 2004/2005 water injection experiment at the KTB/Germany
Modeling a fluid injection into the pilot hole of the "Kontinentale Tiefbohrung der Bundesrepublik Deutschland" (KTB) using finite elements
Nucleosomes in serum as a marker for cell death
The concentration of nucleosomes is elevated in blood of patients with diseases which are associated with enhanced cell death. In order to detect these circulating nucleosomes, we used the Cell Death Detection-ELISA(Plus) (CDDE) from Roche Diagnostics (Mannheim, Germany) (details at http:\textbackslash{}\textbackslash{}biochem.roche.com). For its application in liquid materials we performed various modifications: we introduced a standard curve with nucleosome-rich material, which enabled direct quantification and improved comparability of the values within (CVinterassay:3.0-4.1%) and between several runs (CVinterassay:8.6-13.5%), and tested the analytical specificity of the ELISA. Because of the fast elimination of nucleosomes from circulation and their limited stability, we compared plasma and serum matrix and investigated in detail the pre-analytical handling of serum samples which can considerably influence the test results. Careless venipuncture producing hemolysis, delayed centrifugation and bacterial contamination of the blood samples led to false-positive results; delayed stabilization with EDTA and insufficient storage conditions resulted in false-negative values. At temperatures of -20 degreesC, serum samples which were treated with 10 mM EDTA were stable for at least 6 months. In order to avoid possible interfering factors, we recommend a schedule for the pre-analytical handling of the samples. As the first stage, the possible clinical application was investigated in the sera of 310 persons. Patients with solid tumors (n = 220; mean = 361 Arbitrary Units (AU)) had considerably higher values than healthy persons (n = 50; mean = 30 AU; P = 0.0001) and patients with inflammatory diseases (n = 40; mean = 296 AU; p = 0.096). Within the group of patients with tumors, those in advanced stages (UICC 4) showed significantly higher values than those in early stages (UICC 1-3) (P = 0.0004)
Groundwater modeling in shales at a steep hill near Jena
Water flow and water storage in hill slopes have a strong interest in the hydrological scientific community. The use of the gravimetrical signal of superconducting gravimeters can help to understand water flow in such areas. At the Geodynamic Observatory Moxa of the Friedrich Schiller University Jena (Germany), the relation between hill slope hydrological processes and gravity residuals are investigated. For this purpose a linear reservoir model was developed to quantify canopy storage and storage changes in the unsaturated zone. A groundwater flow model (MODFLOW) was developed to quantify flow in fractured shales. Cross correlation showed significant gravimetrical response on heavy precipitation events after a dry period. The groundwater model simulated the expected flow patterns reasonably well
Analysis of the intraspinal calcium dynamics and its implications on the plasticity of spiking neurons
The influx of calcium ions into the dendritic spines through the
N-metyl-D-aspartate (NMDA) channels is believed to be the primary trigger for
various forms of synaptic plasticity. In this paper, the authors calculate
analytically the mean values of the calcium transients elicited by a spiking
neuron undergoing a simple model of ionic currents and back-propagating action
potentials. The relative variability of these transients, due to the stochastic
nature of synaptic transmission, is further considered using a simple Markov
model of NMDA receptos. One finds that both the mean value and the variability
depend on the timing between pre- and postsynaptic action-potentials. These
results could have implications on the expected form of synaptic-plasticity
curve and can form a basis for a unified theory of spike time-dependent, and
rate based plasticity.Comment: 14 pages, 10 figures. A few changes in section IV and addition of a
new figur
Dense 4D nanoscale reconstruction of living brain tissue
Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue
Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease
Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive muscle weakness. The disease is caused by mutations in the acid α-glucosidase (GAA) gene. Despite the currently available enzyme replacement therapy (ERT), roughly half of the infants with Pompe disease die before the age of 3 years. Limitations of ERT are immune responses to the recombinant enzyme, incomplete correction of the disease phenotype, lifelong administration, and inability of the enzyme to cross the blood-brain barrier. We previously reported normalization of glycogen in heart tissue and partial correction of the skeletal muscle phenotype by ex vivo hematopoietic stem cell gene therapy. In the present study, using a codon-optimized GAA (GAAco), the enzyme levels resulted in close to normalization of glycogen in heart, muscles, and brain, and in complete normalization of motor function. A large proportion of microglia in the brain was shown to be GAA positive. All astrocytes contained the enzyme, which is in line with mannose-6-phosphate receptor expression and the key role in glycogen storage and glucose metabolism. The lentiviral vector insertion site analysis confirmed no preference for integration near proto-oncogenes. This correction of murine Pompe disease warrants further development toward a cure of the human condition.This publication reports that stem cell gene therapy using a codon-optimized gene encoding acid α-glucosidase (GAA) cures the mouse model of Pompe disease, a lysosomal storage disorder
Absolute response of Fuji imaging plate detectors to picosecond-electron bunches
The characterization of the absolute number of electrons generated by laser wakefield acceleration often relies on absolutely calibrated FUJI imaging plates (IP), although their validity in the regime of extreme peak currents is untested. Here, we present an extensive study on the dependence of the sensitivity of BAS-SR and BAS-MS IP to picosecond electron bunches of varying charge of up to 60 pC, performed at the electron accelerator ELBE, making use of about three orders of magnitude of higher peak intensity than in prior studies. We demonstrate that the response of the IPs shows no saturation effect and that the BAS-SR IP sensitivity of 0.0081 photostimulated luminescence per electron number confirms surprisingly well data from previous works. However, the use of the identical readout system and handling procedures turned out to be crucial and, if unnoticed, may be an important error source
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