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Global Metabolic Shifts in Age and Alzheimer's Disease Mouse Brains Pivot at NAD+/NADH Redox Sites.
Age and Alzheimer's disease (AD) share some common features such as cognitive impairments, memory loss, metabolic disturbances, bioenergetic deficits, and inflammation. Yet little is known on how systematic shifts in metabolic networks depend on age and AD. In this work, we investigated the global metabolomic alterations in non-transgenic (NTg) and triple-transgenic (3xTg-AD) mouse brain hippocampus as a function of age by using untargeted Ultrahigh Performance Liquid Chromatography-tandem Mass Spectroscopy (UPLC-MS/MS). We observed common metabolic patterns with aging in both NTg and 3xTg-AD brains involved in energy-generating pathways, fatty acids oxidation, glutamate, and sphingolipid metabolism. We found age-related downregulation of metabolites from reactions in glycolysis that consumed ATP and in the TCA cycle, especially at NAD+/NADH-dependent redox sites, where age- and AD-associated limitations in the free NADH may alter reactions. Conversely, metabolites increased in glycolytic reactions in which ATP is produced. With age, inputs to the TCA cycle were increased including fatty acid β-oxidation and glutamine. Overall age- and AD-related changes were > 2-fold when comparing the declines of upstream metabolites of NAD+/NADH-dependent reactions to the increases of downstream metabolites (p = 10-5, n = 8 redox reactions). Inflammatory metabolites such as ceramides and sphingosine-1-phosphate also increased with age. Age-related decreases in glutamate, GABA, and sphingolipid were seen which worsened with AD genetic load in 3xTg-AD brains, possibly contributing to synaptic, learning- and memory-related deficits. The data support the novel hypothesis that age- and AD-associated metabolic shifts respond to NAD(P)+/NAD(P)H redox-dependent reactions, which may contribute to decreased energetic capacity
Explanation and observability of diffraction in time
Diffraction in time (DIT) is a fundamental phenomenon in quantum dynamics due
to time-dependent obstacles and slits. It is formally analogous to diffraction
of light, and is expected to play an increasing role to design coherent matter
wave sources, as in the atom laser, to analyze time-of-flight information and
emission from ultrafast pulsed excitations, and in applications of coherent
matter waves in integrated atom-optical circuits. We demonstrate that DIT
emerges robustly in quantum waves emitted by an exponentially decaying source
and provide a simple explanation of the phenomenon, as an interference of two
characteristic velocities. This allows for its controllability and
optimization.Comment: 4 pages, 6 figure
Co-digestion of source segregated domestic food waste to improve process stability
Cattle slurry and card packaging were used to improve the operational stability of food waste digestion, with the aim of reducing digestate total ammoniacal nitrogen concentrations compared to food waste only. Use of cattle slurry could have major environmental benefits through reducing greenhouse gas emissions associated with current management practices; whilst card packaging is closely linked to food waste and could be co-collected as a source segregated material. Both options increase the renewable energy potential whilst retaining organic matter and nutrients for soil replenishment. Co-digestion allowed higher organic loadings and gave a more stable process. A high ammonia inoculum acclimated more readily to cattle slurry than card packaging, probably through supplementation by trace elements and micro-organisms. Long-term operation at a 75-litre scale showed a characteristic pattern of volatile fatty acid accumulation in mono-digestion of food waste, and allowed performance parameters to be determined for the co-digestion substrates.<br/
Rotational properties of nuclei around No investigated using a spectroscopic-quality Skyrme energy density functional
Nuclei in the mass region represent the heaviest systems where
detailed spectroscopic information is experimentally available. Although
microscopic-macroscopic and self-consistent models have achieved great success
in describing the data in this mass region, a fully satisfying precise
theoretical description is still missing.
By using fine-tuned parametrizations of the energy density functionals, the
present work aims at an improved description of the single-particle properties
and rotational bands in the nobelium region. Such locally optimized
parameterizations may have better properties when extrapolating towards the
superheavy region.
Skyrme-Hartree-Fock-Bogolyubov and Lipkin-Nogami methods were used to
calculate the quasiparticle energies and rotational bands of nuclei in the
nobelium region. Starting from the most recent Skyrme parametrization, UNEDF1,
the spin-orbit coupling constants and pairing strengths have been tuned, so as
to achieve a better agreement with the excitation spectra and odd-even mass
differences in Cf and Bk.
The quasiparticle properties of Cf and Bk were very well
reproduced. At the same time, crucial deformed neutron and proton shell gaps
open up at and , respectively. Rotational bands in Fm, No, and
Rf isotopes, where experimental data are available, were also fairly well
described. To help future improvements towards a more precise description,
small deficiencies of the approach were carefully identified.
In the mass region, larger spin-orbit strengths than those from
global adjustments lead to improved agreement with data. Puzzling effects of
particle-number restoration on the calculated moment of inertia, at odds with
the experimental behaviour, require further scrutiny.Comment: 9 pages, 10 figures; to be published in Physical Review
Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice
Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p\u3c0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure
The high temperature creep deformation of Si3N4-6Y2O3-2Al2O3
The creep properties of silicon nitride containing 6 wt percent yttria and 2 wt percent alumina have been determined in the temperature range 1573 to 1673 K. The stress exponent, n, in the equation epsilon dot varies as sigma sup n, was determined to be 2.00 + or - 0.15 and the true activation energy was found to be 692 + or - 25 kJ/mol. Transmission electron microscopy studies showed that deformation occurred in the grain boundary glassy phase accompanied by microcrack formation and cavitation. The steady state creep results are consistent with a diffusion controlled creep mechanism involving nitrogen diffusion through the grain boundary glassy phase
Deformations and quasiparticle spectra of nuclei in the nobelium region
We have performed self-consistent Skyrme Hartree-Fock-Bogolyubov calculations
for nuclei close to No. Self-consistent deformations, including
as functions of the rotational frequency, were determined for
even-even nuclei Fm, No, and Rf. The
quasiparticle spectra for N=151 isotones and Z=99 isotopes were calculated and
compared with experimental data and the results of Woods-Saxon calculations. We
found that our calculations give high-order deformations similar to those
obtained for the Woods-Saxon potential, and that the experimental quasiparticle
energies are reasonably well reproduced.Comment: 6 pages, 2 figures; ICFN5 conference proceeding
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