Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
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The Earth's thermosphere and ionosphere (TI) are characterized by perpetual variability as integral parts of the atmosphere system, with intermittent disturbances from solar and geomagnetic forcing. ...This review examines how the TI variability is affected by processes originating from the lower atmosphere and implications for quantifying and forecasting the TI. This aspect of the TI variability has been increasingly appreciated in recent years from both observational and numerical studies, especially during the last extended solar minimum. This review focuses on the role of atmospheric waves, including tides, planetary waves, gravity waves, and acoustic waves, which become increasingly significant as they propagate from their source region to the upper atmosphere. Recent studies have led to better understanding of how these waves directly or indirectly affect TI wind, temperature, and compositional structures; the circulation pattern; neutral and ion species transport; and ionospheric wind dynamo. The variability of these waves on daily to interannual scales has been found to significantly impact the TI variability. Several outstanding questions and challenges have been highlighted: (i) large, seemingly stochastic, day‐to‐day variability of tides in the TI; (ii) control of model error in the TI region by the lower atmosphere; and (iii) the increasing importance of processes with shorter spatial and temporal scales at higher altitudes. Addressing these challenges requires model capabilities to assimilate observations of both lower and upper atmosphere and higher model resolution to capture complex interactions among processes over a broad range of scales and extended altitudes.
Key Points
Review the role of waves from lower atmosphere in thermosphere/ionosphere (TI) variability
Elucidate how predictability of the TI is affected by the lower atmosphere
Highlight outstanding questions in studying lower/upper atmosphere coupling
The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. ...However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.
The coupling of the ionosphere to processes from below remains an elusive and difficult problem, as rapidly changing external drivers from above mask variations related to lower atmospheric sources. ...Here we use superposition of unique circumstances, current deep solar minimum and a record‐breaking stratospheric warming event, to gain new insights into causes of ionospheric perturbations. We show large (50–150%) persistent variations in the low‐latitude ionosphere (200–1000 km) that occur several days after a sudden warming event in the high‐latitude winter stratosphere (∼30 km). We rule out solar irradiance and geomagnetic activity as explanations of the observed variation. Using a general circulation model, we interpret these observations in terms of large changes in atmospheric tides from their nonlinear interaction with planetary waves that are strengthened during sudden warmings. We anticipate that further understanding of the coupling processes with planetary waves, accentuated during the stratospheric sudden warming events, has the potential of enabling the forecast of low‐latitude ionospheric weather up to several days in advance.
Large ionospheric variability is found at low to middle latitudes when a quasi‐stationary planetary wave is specified in the winter stratosphere in the National Center for Atmospheric Research ...thermosphere‐ionosphere‐mesosphere electrodynamics general circulation model for solar minimum conditions. The variability includes change of electric field/ion drift, F2 peak density and height, and the total electron content. The electric field/ion drift change is the largest near dawn in the numerical experiments. Analysis of model results suggests that, although the quasi‐stationary planetary wave does not propagate deep into the ionosphere or to low latitudes due to the presence of critical layers and strong molecular dissipation, the planetary wave and tidal interaction leads to large changes in tides, which can strongly impact the ionosphere at low and middle latitudes through the E region wind dynamo. Large zonal gradients of zonal and meridional winds from the tidal components and the zonal gradient of electric conductivities at dawn can produce large convergence/divergence of Hall and Pedersen currents, which in turn produces a polarization electric field. The ionospheric changes are dependent on both the longitude and local time, and are determined by the amplitudes and phases of the superposing wave components. The model results are consistent with observed ionospheric changes at low and middle latitudes during stratospheric sudden warming events, when quasi‐stationary planetary waves become large.
We report the first results of a global ionosphere/thermosphere simulation study that self‐consistently generates large‐scale equatorial spread F (ESF) plasma bubbles in the postsunset ionosphere. ...The coupled model comprises the ionospheric code SAMI3 and the atmosphere/thermosphere code WACCM‐X. Two cases are modeled for different seasons and geophysical conditions: the March case (low solar activity: F10.7 = 70) and the July case (high solar activity: F10.7 = 170). We find that equatorial plasma bubbles formed and penetrated into the topside F layer for the March case but not the July case. For the March case, a series of bubbles formed in the Atlantic sector with irregularity spacings in the range 400–1,200 km, rose to over 800 km, and persisted until after midnight. These results are consistent with recent GOLD observations. Calculation of the generalized Rayleigh‐Taylor instability (GRTI) growth rate shows that the e‐folding time was shorter for the March case than the July case.
Key Points
The first results from a high‐resolution, global simulation of equatorial spread F using realistic thermospheric conditions
The development of equatorial plasma bubbles is both longitudinally and seasonally dependent
Atmospheric waves play an essential role in “seeding” the generalized Rayleigh‐Taylor instability responsible for the instability
We study the response of the thermosphere and ionosphere to gravity waves (GWs) excited by 6 h of deep convection in Brazil on the evening of 01 October 2005 via the use of convective plume, ray ...trace, and global models. We find that primary GWs excited by convection having horizontal wavelengths of λH∼70–300 km, periods of 10–60 min, and phase speeds of cH∼50–225 m/s propagate well into the thermosphere. Their density perturbations are ρ′/ρ¯∼15– 25% at z∼150 km and are negligible at z>300 km. The dissipation of these GWs creates spatially and temporally localized body forces with amplitudes of 0.2– 1.0 m/s2at z∼120–230 km. These forces generate two counter‐rotating circulation cells with horizontal velocities of 50–350 m/s. They also excite secondary GWs; those resolved by our global model have λH∼4000–5000 km and cH∼500–600 m/s. These secondary GWs propagate globally and have ρ′/ρ¯∼10– 25% and 5–15% at z=250 and 375 km, respectively. These forces also create plasma perturbations of foF2′∼0.2–1.0 MHz, TEC′∼0.4– 1.5 TECU (total electron content unit, 1TECU =1016 elm−2), and hmF2′∼5–50 km. The large‐scale traveling ionospheric disturbances (LSTIDs) induced by the secondary GWs have amplitudes of foF2′∼0.2–0.5 MHz, TEC′∼0.2– 0.6 TECU, and hmF2′∼5–10 km. In a companion paper, we discuss changes to the prereversal enhancement and plasma drift from these forces.
Key PointsThe dissipation of GWs creates circulation cells, secondary GWs, LSTIDs
Optical frequency combs act as rulers in the frequency domain and have opened new avenues in many fields such as fundamental time metrology, spectroscopy and frequency synthesis. In particular, ...spectroscopy by means of optical frequency combs has surpassed the precision and speed of Fourier spectrometers. Such a spectroscopy technique is especially relevant for the mid-infrared range, where the fundamental rotational-vibrational bands of most light molecules are found. Most mid-infrared comb sources are based on down-conversion of near-infrared, mode-locked, ultrafast lasers using nonlinear crystals. Their use in frequency comb spectroscopy applications has resulted in an unequalled combination of spectral coverage, resolution and sensitivity. Another means of comb generation is pumping an ultrahigh-quality factor microresonator with a continuous-wave laser. However, these combs depend on a chain of optical components, which limits their use. Therefore, to widen the spectroscopic applications of such mid-infrared combs, a more direct and compact generation scheme, using electrical injection, is preferable. Here we present a compact, broadband, semiconductor frequency comb generator that operates in the mid-infrared. We demonstrate that the modes of a continuous-wave, free-running, broadband quantum cascade laser are phase-locked. Combining mode proliferation based on four-wave mixing with gain provided by the quantum cascade laser leads to a phase relation similar to that of a frequency-modulated laser. The comb centre carrier wavelength is 7 micrometres. We identify a narrow drive current range with intermode beat linewidths narrower than 10 hertz. We find comb bandwidths of 4.4 per cent with an intermode stability of less than or equal to 200 hertz. The intermode beat can be varied over a frequency range of 65 kilohertz by radio-frequency injection. The large gain bandwidth and independent control over the carrier frequency offset and the mode spacing open the way to broadband, compact, all-solid-state mid-infrared spectrometers.
For the first time a mesoscale‐resolving whole atmosphere general circulation model has been developed, using the National Center for Atmospheric Research Whole Atmosphere Community Climate Model ...with ∼0.25° horizontal resolution and 0.1 scale height vertical resolution above the middle stratosphere (higher resolution below). This is made possible by the high accuracy and high scalability of the spectral element dynamical core from the High‐Order Method Modeling Environment. For the simulated January–February period, the latitude‐height structure and the magnitudes of the temperature variance compare well with those deduced from the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) observations. The simulation reveals the increasing dominance of gravity waves (GWs) at higher altitudes through both the height dependence of the kinetic energy spectra, which display a steeper slope (∼−3) in the stratosphere and an increasingly shallower slope above, and the increasing spatial extent of GWs (including a planetary‐scale extent of a concentric GW excited by a tropical cyclone) at higher altitudes. GW impacts on the large‐scale flow are evaluated in terms of zonal mean zonal wind and tides: with no GW drag parameterized in the simulations, forcing by resolved GWs does reverse the summer mesospheric wind, albeit at an altitude higher than climatology, and only slows down the winter mesospheric wind without closing it. The hemispheric structures and magnitudes of diurnal and semidiurnal migrating tides compare favorably with observations.
Key PointsFirst mesoscale‐resolving whole atmosphere general circulation modelSimulation reveals the growing dominance of gravity waves with altitudeGravity waves and their large‐scale impacts evaluated
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