18F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis.

Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2'-deoxy-2'-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures deoxyribonucleoside salvage and accumulates preferentially in immune cells. We hypothesized that 18F-FAC PET could noninvasively image brain-infiltrating leukocytes. Methods: Healthy mice were imaged with 18F-FAC PET to quantify if this radiotracer crosses the blood-brain barrier (BBB). Experimental autoimmune encephalomyelitis (EAE) is a mouse disease model with brain-infiltrating leukocytes. To determine whether 18F-FAC accumulates in brain-infiltrating leukocytes, EAE mice were analyzed with 18F-FAC PET, digital autoradiography, and immunohistochemistry, and deoxyribonucleoside salvage activity in brain-infiltrating leukocytes was analyzed ex vivo. Fingolimod-treated EAE mice were imaged with 18F-FAC PET to assess if this approach can monitor the effect of an immunomodulatory drug on brain-infiltrating leukocytes. PET scans of individuals injected with 2-chloro-2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosyl-adenine (18F-CFA), a PET radiotracer that measures deoxyribonucleoside salvage in humans, were analyzed to evaluate whether 18F-CFA crosses the human BBB. Results: 18F-FAC accumulates in the healthy mouse brain at levels similar to 18F-FAC in the blood (2.54 ± 0.2 and 3.04 ± 0.3 percentage injected dose per gram, respectively) indicating that 18F-FAC crosses the BBB. EAE mice accumulate 18F-FAC in the brain at 180% of the levels of control mice. Brain 18F-FAC accumulation localizes to periventricular regions with significant leukocyte infiltration, and deoxyribonucleoside salvage activity is present at similar levels in brain-infiltrating T and innate immune cells. These data suggest that 18F-FAC accumulates in brain-infiltrating leukocytes in this model. Fingolimod-treated EAE mice accumulate 18F-FAC in the brain at 37% lower levels than control-treated EAE mice, demonstrating that 18F-FAC PET can monitor therapeutic interventions in this mouse model. 18F-CFA accumulates in the human brain at 15% of blood levels (0.08 ± 0.01 and 0.54 ± 0.07 SUV, respectively), indicating that 18F-CFA does not cross the BBB in humans. Conclusion: 18F-FAC PET can visualize brain-infiltrating leukocytes in a mouse MS model and can monitor the response of these cells to an immunomodulatory drug. Translating this strategy into humans will require exploring additional radiotracers

Exciting dark matter in the galactic center

We reconsider the proposal of excited dark matter (DM) as an explanation for excess 511 keV gamma rays from positrons in the galactic center. We quantitatively compute the cross section for DM annihilation to nearby excited states, mediated by exchange of a new light gauge boson with off-diagonal couplings to the DM states. In models where both excited states must be heavy enough to decay into e^+ e^- and the ground state, the predicted rate of positron production is never large enough to agree with observations, unless one makes extreme assumptions about the local circular velocity in the Milky Way, or alternatively if there exists a metastable population of DM states which can be excited through a mass gap of less than 650 keV, before decaying into electrons and positrons.Comment: Dedicated to the memory of Lev Kofman; 16 pages, 9 figures; v3 added refs, minor changes, accepted to PR

Combinatorial RNA interference in Caenorhabditis elegans reveals that redundancy between gene duplicates can be maintained for more than 80 million years of evolution

BACKGROUND: Systematic analyses of loss-of-function phenotypes have been carried out for most genes in Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster. Although such studies vastly expand our knowledge of single gene function, they do not address redundancy in genetic networks. Developing tools for the systematic mapping of genetic interactions is thus a key step in exploring the relationship between genotype and phenotype. RESULTS: We established conditions for RNA interference (RNAi) in C. elegans to target multiple genes simultaneously in a high-throughput setting. Using this approach, we can detect the great majority of previously known synthetic genetic interactions. We used this assay to examine the redundancy of duplicated genes in the genome of C. elegans that correspond to single orthologs in S. cerevisiae or D. melanogaster and identified 16 pairs of duplicated genes that have redundant functions. Remarkably, 14 of these redundant gene pairs were duplicated before the divergence of C. elegans and C. briggsae 80-110 million years ago, suggesting that there has been selective pressure to maintain the overlap in function between some gene duplicates. CONCLUSION: We established a high throughput method for examining genetic interactions using combinatorial RNAi in C. elegans. Using this technique, we demonstrated that many duplicated genes can retain redundant functions for more than 80 million years of evolution. This provides strong support for evolutionary models that predict that genetic redundancy between duplicated genes can be actively maintained by natural selection and is not just a transient side effect of recent gene duplication events

Radiation-induced growth and isothermal decay of infrared-stimulated luminescence from feldspar

Optically stimulated luminescence (OSL) ages can determine a wide range of geological events or processes, such as the timing of sediment deposition, the exposure duration of a rock surface, or the cooling rate of bedrock. The accuracy of OSL dating critically depends on our capability to describe the growth and decay of laboratory-regenerated luminescence signals. Here we review a selection of common models describing the response of infrared stimulated luminescence (IRSL) of feldspar to constant radiation and temperature as administered in the laboratory. We use this opportunity to introduce a general-order kinetic model that successfully captures the behaviour of different materials and experimental conditions with a minimum of model parameters, and thus appears suitable for future application and validation in natural environments. Finally, we evaluate all the presented models by their ability to accurately describe a recently published feldspar multi-elevated temperature post-IR IRSL (MET-pIRIR) dataset, and highlight each model's strengths and shortfalls

Acculturation is associated with left ventricular mass in a multiethnic sample: the Multi-Ethnic Study of Atherosclerosis.

BackgroundAcculturation involves stress-related processes and health behavioral changes, which may have an effect on left ventricular (LV) mass, a risk factor for cardiovascular disease (CVD). We examined the relationship between acculturation and LV mass in a multiethnic cohort of White, African-American, Hispanic and Chinese subjects.MethodsCardiac magnetic resonance assessment was available for 5004 men and women, free of clinical CVD at baseline. Left ventricular mass index was evaluated as LV mass indexed by body surface area. Acculturation was characterized based on language spoken at home, place of birth and length of stay in the United States (U.S.), and a summary acculturation score ranging from 0 = least acculturated to 5 = most acculturated. Mean LV mass index adjusted for traditional CVD risk factors was compared across acculturation levels.ResultsUnadjusted mean LV mass index was 78.0 ± 16.3 g/m(2). In adjusted analyses, speaking exclusively English at home compared to non-English language was associated with higher LV mass index (81.3 ± 0.4 g/m(2) vs 79.9 ± 0.5 g/m(2), p = 0.02). Among foreign-born participants, having lived in the U.S. for ≥ 20 years compared to < 10 years was associated with greater LV mass index (81.6 ± 0.7 g/m(2) vs 79.5 ± 1.1 g/m(2), p = 0.02). Compared to those with the lowest acculturation score, those with the highest score had greater LV mass index (78.9 ± 1.1 g/m(2) vs 81.1 ± 0.4 g/m(2), p = 0.002). There was heterogeneity in which measure of acculturation was associated with LV mass index across ethnic groups.ConclusionsGreater acculturation is associated with increased LV mass index in this multiethnic cohort. Acculturation may involve stress-related processes as well as behavioral changes with a negative effect on cardiovascular health

Constraining properties of neutron stars with heavy-ion reactions in terrestrial laboratories

Heavy-ion reactions provide a unique means to investigate the equation of state (EOS) of neutron-rich nuclear matter, especially the density dependence of the nuclear symmetry energy $E_{sym}(\rho)$. The latter plays an important role in understanding many key issues in both nuclear physics and astrophysics. Recent analyses of heavy-ion reactions have already put a stringent constraint on the $E_{sym}(\rho)$ around the saturation density. This subsequently allowed us to constrain significantly the radii and cooling mechanisms of neutron stars as well as the possible changing rate of the gravitational constant G.Comment: 6 pages. Talk given at the Nuclear Physics in Astrophysics III, Dresden, Germany, March 26-31, 2007. To appear in a special volume of J. of Phys.

Escape from an optoelectronic tweezer trap: experimental results and simulations

Optoelectronic tweezers (OET) are a microsystem actuation technology capable of moving microparticles at mm s−1 velocities with nN forces. In this work, we analyze the behavior of particles manipulated by negative dielectrophoresis (DEP) forces in an OET trap. A user-friendly computer interface was developed to generate a circular rotating light pattern to control the movement of the particles, allowing their force profiles to be conveniently measured. Three-dimensional simulations were carried out to clarify the experimental results, and the DEP forces acting on the particles were simulated by integrating the Maxwell stress tensor. The simulations matched the experimental results and enabled the determination of a new “hopping” mechanism for particle-escape from the trap. As indicated by the simulations, there exists a vertical DEP force at the edge of the light pattern that pushes up particles to a region with a smaller horizontal DEP force. We propose that this phenomenon will be important to consider for the design of OET micromanipulation experiments for a wide range of applications

Methane and Protein from Beef Cattle Manure

Dwindling supplies of conventional fossil fuels have prompted renewed interest in recovering energy through the bioconversion of waste organic materials. The large quantities of manure produced in confinement feedlots and the need to manage this manure effectively make feedlots a logical choice for assessing the feasibility of recovering methane and protein through anaerobic fermentation. Research at U.S. Meat Animal Research Center is designed to determine the technical and economic feasibility of recovering methane and protein from beef cattle manure. Specific Objectives are to: 1. Develop design criteria for optimum production of methane and protein through anaerobic fermentation of beef cattle manure, 2. Develop efficient methods to recover high protein biomass from the fermented residue, 3. Evaluate the nutritional value of the biomass as a livestock feed, 4. Determine the capital and operational costs and energy, man-power, and safety requirements for methane fermentation systems associated with livestock operations. This project was initiated in 1976 and is jointly funded by the U.S. Department of Agriculture, Agricultural Research Service, and the U.S. Department of Energy through the Solar Energy Research Institute

Data assimilative modeling investigation of Gulf Stream Warm Core Ring interaction with continental shelf and slope circulation

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 119 (2014): 5968–5991, doi:10.1002/2014JC009898.A data assimilative ocean circulation model is used to hindcast the interaction between a large Gulf Stream Warm Core Ring (WCR) with the Mid-Atlantic Bight (MAB) shelf and slope circulation. Using the recently developed Incremental Strong constraint 4D Variational (I4D-Var) data assimilation algorithm, the model assimilates mapped satellite sea surface height (SSH), sea surface temperature (SST), in situ temperature, and salinity profiles measured by expendable bathythermograph, Argo floats, shipboard CTD casts, and glider transects. Model validations against independent hydrographic data show 60% and 57% error reductions in temperature and salinity, respectively. The WCR significantly changed MAB continental slope and shelf circulation. The mean cross-shelf transport induced by the WCR is estimated to be 0.28 Sv offshore, balancing the mean along-shelf transport by the shelfbreak jet. Large heat/salt fluxes with peak values of 8900 W m−2/4 × 10−4 kg m−2 s−1 are found when the WCR was impinging upon the shelfbreak. Vorticity analysis reveals the nonlinear advection term, as well as the residual of joint effect of baroclinicity and bottom relief (JEBAR) and advection of potential vorticity (APV) play important roles in controlling the variability of the eddy vorticity.Research support provided through ONR grants N00014-06-1-0739, N00014-10-1-0367, and NSF grant OCE-0927470 is much appreciated. B. Powell was supported by ONR grant N00014-09-10939. K. Chen was supported by the Woods Hole Oceanographic Institution Postdoctoral Scholar Program.2015-03-1