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/

Anaerobic digestion of two biodegradable municipal waste streams

Landfill avoidance for organic wastes is now a high priority worldwide. Two fractions of the municipal waste stream were considered with respect to their potential for diversion through controlled anaerobic digestion. The physical and chemical properties of source segregated domestic food waste (ss-FW) and of the mechanically-recovered organic fraction of municipal solid waste (mr-OFMSW) were analysed, and their methane yields determined in both batch and semi-continuous digestion. Methane potentials were compared with predicted values based on biochemical composition, elemental analysis and carbon mass balance, and the differences explained by compositional analysis of feedstocks and digestates. The ss-FW had a higher percentage biodegradability and higher energy potential on a dry weight basis due to the high proportion of proteins and fats in this waste, although the energy potential of the mr-OFMSW was slightly higher on a wet weight (WW) basis. The mr-OFMSW showed very stable digestion characteristics, whereas the ss-FW had a high digestate ammoniacal-N concentration and volatile fatty acid accumulation leading to some process instability. Digestates from semi-continuous trials with mr-OFMSW had high concentrations of potentially toxic elements (PTE) and a lower nutrient content than ss-FW digestate, making the former unsuitable for application to land used in food productio

Cointegration Between Prices of Pecans and Other Edible Nuts: Forecasting and Implications

Crop Production/Industries, Demand and Price Analysis,

Rotational properties of nuclei around 254^{254}No investigated using a spectroscopic-quality Skyrme energy density functional

Nuclei in the $Z\approx100$ 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 $^{251}$Cf and $^{249}$Bk. The quasiparticle properties of $^{251}$Cf and $^{249}$Bk were very well reproduced. At the same time, crucial deformed neutron and proton shell gaps open up at $N=152$ and $Z=100$, 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 $Z\approx100$ 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

Shaping of molecular weight distribution by iterative learning probability density function control strategies

A mathematical model is developed for the molecular weight distribution (MWD) of free-radical styrene polymerization in a simulated semi-batch reactor system. The generation function technique and moment method are employed to establish the MWD model in the form of Schultz-Zimmdistribution. Both static and dynamic models are described in detail. In order to achieve the closed-loop MWD shaping by output probability density function (PDF) control, the dynamic MWD model is further developed by a linear B-spline approximation. Based on the general form of the B-spline MWD model, iterative learning PDF control strategies have been investigated in order to improve the MWD control performance. Discussions on the simulation studies show the advantages and limitations of the methodology

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