Metabolomics in Early Alzheimer's Disease: Identification of Altered Plasma Sphingolipidome Using Shotgun Lipidomics

The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and inflammatory stress related neuronal apoptosis; however few studies have conducted a comprehensive analysis of the sphingolipidome in AD plasma using analytical platforms with accuracy, sensitivity and reproducibility.We prospectively analyzed plasma from 26 AD patients (mean MMSE 21) and 26 cognitively normal controls in a non-targeted approach using multi-dimensional mass spectrometry-based shotgun lipidomics to determine the levels of over 800 molecular species of lipids. These data were then correlated with diagnosis, apolipoprotein E4 genotype and cognitive performance. Plasma levels of species of sphingolipids were significantly altered in AD. Of the 33 sphingomyelin species tested, 8 molecular species, particularly those containing long aliphatic chains such as 22 and 24 carbon atoms, were significantly lower (p<0.05) in AD compared to controls. Levels of 2 ceramide species (N16:0 and N21:0) were significantly higher in AD (p<0.05) with a similar, but weaker, trend for 5 other species. Ratios of ceramide to sphingomyelin species containing identical fatty acyl chains differed significantly between AD patients and controls. MMSE scores were correlated with altered mass levels of both N20:2 SM and OH-N25:0 ceramides (p<0.004) though lipid abnormalities were observed in mild and moderate AD. Within AD subjects, there were also genotype specific differences.In this prospective study, we used a sensitive multimodality platform to identify and characterize an essentially uniform but opposite pattern of disruption in sphingomyelin and ceramide mass levels in AD plasma. Given the role of brain sphingolipids in neuronal function, our findings provide new insights into the AD sphingolipidome and the potential use of metabolomic signatures as peripheral biomarkers

Lipoxin A4 preconditioning attenuates intestinal ischemia reperfusion injury through Keap1/Nrf2 pathway in a lipoxin A4 receptor independent manner

published_or_final_versio

Pulse Dynamics of an All-Normal-Dispersion Ring Fiber Laser Under Four Different Pulse Regimes

Based on the coupled Ginzburg-Landau equations and Jones matrices of the waveplates considered, a numerical model of an all-normal-dispersion fiber laser mode-locked by nonlinear polarization rotation has been proposed. The operating characteristics of the fiber laser discussed were studied numerically. It has been found that the proposed all-normal-dispersion mode-locked fiber laser (AND-MLFL) could deliver dissipative solitons (DSs) with a M-shaped and U-shaped spectrum, the splitting pulse with a divided spectrum and the amplifier similaritons. The evolution of the intra-cavity pulse and spectrum has been calculated under different regimes and the effects of group velocity dispersion (GVD) and nonlinearity are analyzed. When the fiber laser delivers DSs or causes pulse splitting, nonlinear effects dominate the pulse evolution. With the increase of the accumulated nonlinear phase shift, the operation states change from DS with a M-shaped spectrum to a U-shaped spectrum, and then to the splitting pulse. In the case of amplifier similaritons, both the GVD and nonlinearity play important roles in pulse evolution. The effect of nonlinear polarization rotation and filtering on the pulse reshaping has been analyzed. When the fiber laser delivers DSs with a M-shaped spectrum, the filter has a very weak effect on the pulse and on spectral reshaping. However, when the fiber laser operates in the amplifier similariton state, the filter plays a key role in pulse and spectral reshaping, whereas the nonlinear polarization rotation become less dominant. The dependence of the operational states on the filter bandwidth, fiber length, small signal gain coefficient and orientation of waveplates has also been calculated. A Yb-doped doubled-cladding fiber laser, mode-locked by nonlinear polarization rotation, has also been demonstrated and all of the four pulse regimes are obtained experimentally

MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which induced by ischaemia/reperfusion injury in vivo and in vitro

published_or_final_versio

Pair production of charged Higgs bosons in the Left-Right Twin Higgs model at the ILC and LHC

Left-Right twin Higgs(LRTH) model predicts the existence of a pair of charged Higgs $\phi^{\pm}$. In this paper, we study the production of the charged Higgs bosons pair $\phi^{\pm}$ via the process $e^{+}e^{-}\to \phi^{+}\phi^{-}$ at the International Linear Collider(ILC). The numerical results show that the production rates are at the level of several tens fb, this process can produce the adequate distinct multi-jet final states and the SM background can be efficiently reduced. We also discuss the charged Higgs boson pair production via the process $q\bar{q}\to \phi^{+}\phi^{-}$ at the $CERN$ Large Hadron Collider(LHC) and estimate there production rates. We find that, as long as the charged Higgs bosons are not too heavy, they can be abundantly produced at the LHC. The possible signatures of these new particles might be detected at the ILC and LHC experiments.Comment: 15 pages, 5 figures, discussion extended, reference added, typos fixed, revised version to be published in Eur.Phys.J.

Preclinical evaluation of the safety and pathogenicity of a live attenuated recombinant influenza A/H7N9 seed strain and corresponding MF59-adjuvanted split vaccine

published_or_final_versio

Magnetic Excitations of Undoped Iron Oxypnictides

We study the magnetic excitations of undoped iron oxypnictides using a three-dimensional Heisenberg model with single-ion anisotropy. Analytic forms of the spin wave dispersion, velocities, and structure factor are given. Aside from quantitative comparisons which can be made to inelastic neutron scattering experiments, we also give qualitative criteria which can distinguish various regimes of coupling strength. The magnetization reduction due to quantum zero point fluctuations shows clear dependence on the c-axis coupling.Comment: 4 pages, 5 figures, to appear in Frontiers of Physics in China: a special issue on Iron-based superconductor

The applied anatomy and clinical significance of the proximal, V1 segment of vertebral artery

Background: The aim of the study was to probe the morphological features of the proximal segment (V1) of vertebral artery (VA) in a sample of Chinese cadavers. Materials and methods: The origin, course and outer diameter at origin of the pre-vertebral part of the VAs were evaluated in 119 adult cadavers. Results: It was found that 94.12% of the VAs originated from the subclavian arteries, bilaterally. The variant origins were present in 5.88% of the cadavers and all originated directly from the arch of the aorta. All the variations were observed on the left side of male cadavers. The average outer diameters at origin of the normal and variation groups were 4.35 ± 1.00 mm and 4.82 ± ± 1.42 mm, respectively, p = 0.035. In the normal group, but not in the variation group, the average diameter in the males was significantly larger than that in the females (4.50 ± 0.99 mm, 3.92 ± 0.92 mm, respectively, p = 0.000). In addition, only 5 cadavers in the normal group had hypoplastic VAs (4.20%, 4 males, 3 right-sided). Vertebral artery dominance (VAD) was present in 91 (69 males) out of 112 cadavers and more common on the left (n = 48). In addition, 3 cadavers satisfied conditions for coexistence of VAD and vertebral artery hypoplasia. All 7 cadavers in the variation group exhibited VAD, which was more common on the right side (n = 5). Conclusions: The morphologic variations and frequencies described above have implications for the early prevention, abnormal anatomy detection, accurate diagnosis, safe surgery and endovascular treatment of cardiovascular and neurological disease

The development of Y Ba2Cu3Ox thin films using a fluorine-free sol–gel approach for coated conductors

Despite great success in the TFA methods of depositing Y Ba2Cu3Ox (YBCO) thin films for coated conductors, critical issues involved in removing BaCO3 have not entirely been settled. There could be other possible ways of dealing with carbon that remains in the film. We have recently developed a fluorine-free sol–gel synthesis with several important advantages including precursor solution stability, improved film density, and elimination of HF during processing. With this approach, high-quality YBCO films have been developed on single crystal substrates with the transport Jc s up to 106 A cm−2. In this study, the precursor solution stoichiometry was altered and its effects on superconducting properties were studied. The fluorine-free sol–gel-derived films on the LaAlO3 (LAO) substrate exhibited epitaxial growth with excellent in- and out-of-plane texture. Experimental details are reported on the sol–gel synthesis chemistry and XRD and TEM characterization of the YBCO thin films. Also discussed is the underlying formation mechanism of the YBCO phase during the synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48992/2/sust4_12_011.pd

Exact results on the Kitaev model on a hexagonal lattice: spin states, string and brane correlators, and anyonic excitations

In this work, we illustrate how a Jordan-Wigner transformation combined with symmetry considerations enables a direct solution of Kitaev's model on the honeycomb lattice. We (i) express the p-wave type fermionic ground states of this system in terms of the original spins, (ii) adduce that symmetry alone dictates the existence of string and planar brane type correlators and their composites, (iii) compute the value of such non-local correlators by employing the Jordan-Wigner transformation, (iv) affirm that the spectrum is inconsequential to the existence of topological quantum order and that such information is encoded in the states themselves, and (v) express the anyonic character of the excitations in this system and the local symmetries that it harbors in terms of fermions.Comment: 14 pages, 7 figure