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 $(1.0\substack{+0.8-0.4})$ $\times 10^6$ A/(m$^2$ sr eV) was achieved with a beam flux equivalent to $(0.6\substack{+0.3-0.2})$ nA. The temperature of the beam is further reduced with an optical molasses after the 2D MOT. This increased the equivalent brightness to $(6\substack{+5-2})$$\times 10^6$ A/(m$^2$ 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 $t/U$ 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