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Accelerated epigenetic aging in Werner syndrome.
Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown
Fixed-Node Monte Carlo Calculations for the 1d Kondo Lattice Model
The effectiveness of the recently developed Fixed-Node Quantum Monte Carlo
method for lattice fermions, developed by van Leeuwen and co-workers, is tested
by applying it to the 1D Kondo lattice, an example of a one-dimensional model
with a sign problem. The principles of this method and its implementation for
the Kondo Lattice Model are discussed in detail. We compare the fixed-node
upper bound for the ground state energy at half filling with
exact-diagonalization results from the literature, and determine several spin
correlation functions. Our `best estimates' for the ground state correlation
functions do not depend sensitively on the input trial wave function of the
fixed-node projection, and are reasonably close to the exact values. We also
calculate the spin gap of the model with the Fixed-Node Monte Carlo method. For
this it is necessary to use a many-Slater-determinant trial state. The
lowest-energy spin excitation is a running spin soliton with wave number pi, in
agreement with earlier calculations.Comment: 19 pages, revtex, contribution to Festschrift for Hans van Leeuwe
Methylation Status of Imprinted Genes and Repetitive Elements in Sperm DNA from Infertile Males
Stochastic, environmentally and/or genetically induced disturbances in the genome-wide epigenetic reprogramming processes during male germ-cell development may contribute to male infertility. To test this hypothesis, we have studied the methylation levels of 2 paternally (H19 and GTL2) and 5 maternally methylated (LIT1, MEST, NESPAS, PEG3, and SNRPN) imprinted genes, as well as of ALU and LINE1 repetitive elements in 141 sperm samples, which were used for assisted reproductive technologies (ART), including 106 couples with strictly male-factor or combined male and female infertility and 28 couples with strictly female-factor infertility. Aberrant methylation imprints showed a significant association with abnormal semen parameters, but did not seem to influence ART outcome. Repeat methylation also differed significantly between sperm samples from infertile and presumably fertile males. However, in contrast to imprinted genes, ALU methylation had a significant impact on pregnancy and live-birth rate in couples with male-factor or combined infertility. ALU methylation was significantly high-er in sperm samples leading to pregnancy and live-birth than in those that did not. Sperm samples leading to abortions showed significantly lower ALU methylation levels than those leading to the birth of a baby. Copyright (C) 2011 S. Karger AG, Base
Implementation of satellite-based data for improving predictions of arsenic contamination in groundwater in the Red River Delta in Vietnam
Natural arsenic contamination of groundwater aquifers is globally widespread, and particularly poses a problem in regions where groundwater is the main source of drinking and cooking water. Arsenic poisoning can lead to a myriad of serious health effects such as diseases of blood vessels, diabetes and cancers. The aquifers of the Red River Delta in Vietnam are highly contaminated with arsenic and it has been estimated that in this area, around 3 million people are affected by high arsenic concentrations (> 10 \ub5g/L, WHO guideline value; Winkel et al., 2011). Previously, predictions of arsenic contamination in the Red River Delta were established via geospatial modelling using arsenic measurements, as well as surface and 3D-geology. Based on these predictions, probability maps of arsenic at specific depths were created. By comparing these depthresolved probabilities to measured arsenic concentrations, a drawdown of arsenic-enriched waters from Holocene aquifers to previously uncontaminated Pleistocene aquifers was observed. This finding indicated that arsenic contamination has been exacerbated by excessive groundwater pumping rates (Winkel et al., 2011). Furthermore, in a study conducted in the Mekong delta, it was hypothesized that groundwater extraction causes interbedded clays to compact, thereby releasing water containing dissolved arsenic that is subsequently transported to deeper aquifers (Erban et al., 2013). Such human-induced changes cannot be captured by the previous predictive models based on natural predictive parameters mentioned above, leading to erroneous predictions of the arsenic content in areas affected by urbanization, especially in deeper aquifers. To improve predictions in human-affected regions we are using satellite data and remote sensing techniques that enable detection of changes of urban and suburban extents (Nghiem et al., 2009) and vertical build-up (Mathews et al., 2019). Those data and techniques in combination with geochemical and environmental data can help in i) resolving mechanisms behind arsenic mobilization in aquifers due to increased pumping rates and ii) making predictions of arsenic contamination more accurate, especially in areas characterized by increased groundwater pumping
Optimization of Gutzwiller Wavefunctions in Quantum Monte Carlo
Gutzwiller functions are popular variational wavefunctions for correlated
electrons in Hubbard models. Following the variational principle, we are
interested in the Gutzwiller parameters that minimize e.g. the expectation
value of the energy. Rewriting the expectation value as a rational function in
the Gutzwiller parameters, we find a very efficient way for performing that
minimization. The method can be used to optimize general Gutzwiller-type
wavefunctions both, in variational and in fixed-node diffusion Monte Carlo.Comment: 9 pages RevTeX with 10 eps figure
Direct magneto-optical compression of an effusive atomic beam for high-resolution focused ion beam application
An atomic rubidium beam formed in a 70 mm long two-dimensional
magneto-optical trap (2D MOT), directly loaded from a collimated Knudsen
source, is analyzed using laser-induced fluorescence. The longitudinal velocity
distribution, the transverse temperature and the flux of the atomic beam are
reported. The equivalent transverse reduced brightness of an ion beam with
similar properties as the atomic beam is calculated because the beam is
developed to be photoionized and applied in a focused ion beam. In a single
two-dimensional magneto-optical trapping step an equivalent transverse reduced
brightness of A/(m sr eV) was
achieved with a beam flux equivalent to nA. The
temperature of the beam is further reduced with an optical molasses after the
2D MOT. This increased the equivalent brightness to A/(m sr eV). For currents below 10 pA, for which disorder-induced
heating can be suppressed, this number is also a good estimate of the ion beam
brightness that can be expected. Such an ion beam brightness would be a six
times improvement over the liquid metal ion source and could improve the
resolution in focused ion beam nanofabrication.Comment: 10 pages, 8 figures, 1 tabl
Helicity Modulus and Effective Hopping in the Two-Dimensional Hubbard Model Using Slave-Boson Methods
The slave-boson mean-field method is used to study the two-dimensional
Hubbard model. A magnetic phase diagram allowing for paramagnetism, weak- and
strong ferromagnetism and antiferromagnetism, including all continuous and
first-order transitions, is constructed and compared to the corresponding phase
diagram using the Hartree-Fock approximation (HFA). Magnetically ordered
regions are reduced by a factor of about 3 along both the and density
axes compared to the HFA. Using the spin-rotation invariant formulation of the
slave-boson method the helicity modulus is computed and for half-filling is
found to practically coincide with that found using variational Monte Carlo
calculations using the Gutzwiller wave function. Off half-filling the results
can be used to compare with Quantum Monte Carlo calculations of the effective
hopping parameter. Contrary to the case of half-filling, the slave-boson
approach is seen to greatly improve the results of the HFA when off
half-filling. (Submitted to: Journal of Physics: Condensed Matter)Comment: 27 pages, LaTeX2e, 7 figures available upon request, INLO-PUB-10/9
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