High-latitude E Region Ionosphere-thermosphere Coupling: A Comparative Study Using in Situ and Incoherent Scatter Radar Observations

We present in situ and ground-based measurements of the ratio k of ion cyclotronangular frequency to ion-neutral momentum transfer collision frequency to investigateionosphere-thermosphere (IT) coupling in the auroral E region. In situ observations were obtained by NASA sounding rocket 36.234, which was launched into the nightsideE region ionosphere at 1229 UT on 19 January 2007 from Poker Flat, AK. The payload carried instrumentation to determine ion drift angle and electric field vectors. Neutral winds were measured by triangulating a chemical tracer released from rocket 41.064 launched two minutes later. k is calculated from the rotation of the ion drift angle relative to the E-cross-B drift direction in a frame co-rotating with the payload. Between the altitudes of 118 km and 130 km k increases exponentially with a scale height of 9.3 +/- 0.7 km, deviating from an exponential above 130 km. k = 1 at an altitude z(sub0) of 119.9 +/- 0.5 km. The ratio was also estimated from Poker Flat Incoherent Scatter Radar (PFISR) measurements using the rotation of ion velocity with altitude. Exponential fits to the PFISR measurements made during the flight of 41.064 yield z(sub0) 115.9 +/- 1.2 km and a scale height of 9.1 +/- 1.0 km. Differences between in situ and ground-based measurements show that the E region atmospheric densities were structured vertically and/or horizontally on scales of 1 km to 10 km. There were no signs of ionospheric structure in ion density or ion temperature below scales of 1 km. The observations demonstrate the accuracy with which the in situ and PFISR data may be used as probes of IT coupling

Disruption of the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS)-1 inhibits pathophysiological changes in retinal endothelial function in a rat model of diabetes

Our studies have shown that the association between integrin-associated protein (IAP) and SHPS-1 regulates the response of cells including osteoclasts, osteoblasts, smooth muscle and retinal endothelial cells to Insulin-like growth factor-I (IGF-I). The aims of this study were to determine whether the regulation of IGF-I responsiveness by IAP/SHPS-1 association is a generalized response of endothelial cells, to identify the mechanism by which IAP/SHPS-1 association contributes to changes in endothelial cell responses to IGF-I and to determine whether inhibiting their association alters pathophysiologic changes that occur in vivo

Hyperglycemia Enhances IGF-I-Stimulated Src Activation via Increasing Nox4-Derived Reactive Oxygen Species in a PKC -Dependent Manner in Vascular Smooth Muscle Cells

IGF-I–stimulated sarcoma viral oncogene (Src) activation during hyperglycemia is required for propagating downstream signaling. The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I–stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). Nox4 expression was analyzed in VSMCs exposed to hyperglycemia. The role of Nox4-derived reactive oxygen species (ROS) in IGF-I–stimulated Src activation was investigated via knockdown of Nox4. Different isoforms of PKC were screened to investigate their role in hyperglycemia-induced Nox4. The oxidation of Src was shown to be a prerequisite for its activation in response to IGF-I during hyperglycemia. Hyperglycemia induced Nox4, but not Nox1, and p22 phagocyte oxidase (p22phox) expression and IGF-I stimulated Nox4/p22phox complex formation, leading to increased ROS generation. Knockdown of Nox4 prevented ROS generation and impaired the oxidation and activation of Src in response to IGF-I, whereas knockdown of Nox1 had no effect. PKCζ was shown to mediate the hyperglycemia-induced increase in Nox4 expression. The key observations in cultured VSMCs were confirmed in the diabetic mice. Nox4-derived ROS is responsible for the enhancing effect of hyperglycemia on IGF-I–stimulated Src activation, which in turn amplifies IGF-I–linked downstream signaling and biological actions

The Energetic Particle Detector (EPD) Investigation and the Energetic Ion Spectrometer (EIS) for the Magnetospheric Multiscale (MMS) Mission

Abstract The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s magnetosphere as a plasma laboratory. EPD comprises two sensor types, the Energetic Ion Spectrometer (EIS) with one instrument on each of the 4 spacecraft, and the Fly’s Eye Energetic Particle Spectrometer (FEEPS) with 2 instruments on each of the 4 spacecraft. EIS measures energetic ion energy, angle and elemental compositional distributions from a required low energy limit of 20 keV for protons and 45 keV for oxygen ions, up to \u3e0.5 MeV (with capabilities to measure up to \u3e1 MeV). FEEPS measures instantaneous all sky images of energetic electrons from 25 keV to \u3e0.5 MeV, and also measures total ion energy distributions from 45 keV to \u3e0.5 MeV to be used in conjunction with EIS to measure all sky ion distributions. In this report we describe the EPD investigation and the details of the EIS sensor. Specifically we describe EPD-level science objectives, the science and measurement requirements, and the challenges that the EPD team had in meeting these requirements. Here we also describe the design and operation of the EIS instruments, their calibrated performances, and the EIS in-flight and ground operations. Blake et al. (The Flys Eye Energetic Particle Spectrometer (FEEPS) contribution to the Energetic Particle Detector (EPD) investigation of the Magnetospheric Magnetoscale (MMS) Mission, this issue) describe the design and operation of the FEEPS instruments, their calibrated performances, and the FEEPS in-flight and ground operations. The MMS spacecraft will launch in early 2015, and over its 2-year mission will provide comprehensive measurements of magnetic reconnection at Earth’s magnetopause during the 18 months that comprise orbital phase 1, and magnetic reconnection within Earth’s magnetotail during the about 6 months that comprise orbital phase 2

Low Circulating IGF-I Bioactivity in Elderly Men is associated with Increased Mortality

Context: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay (IGF-I KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of circulating IGF-I bioactivity is more informative than levels of immunoreactive IGFI. Objective: To study IGF-I bioactivity in relation to human survival. Design: Prospective observational study. Setting: A clinical research center at a university hospital. Study participants: 376 healthy elderly men (aged 73 to 94 years). Main outcome Measures: IGF-I bioactivity was determined by the IGF-I KIRA. Total and free IGF-I were determined by IGF-I immunoassays. Mortality was registered during follow-up (mean 82 months). Results: During the follow-up period of 8.6 years 170 men (45%) died. Survival of subjects in the highest quartile of IGF-I bioactivity was significantly better than in the lowest quartile, both in the total study group (HR = 1.8, (95% CI: 1.2 − 2.8, p = 0.01) as well as in subgroups having a medical history of cardiovascular disease (HR = 2.4 (95% CI: 1.3 − 4.3, p = 0.003) or a high inflammatory risk profile (HR = 2.3 (95% CI: 1.2 − 4.5, p = 0.01). Significant relationships were not observed for total or free IGF-I. Conclusion: Our study suggests that a relatively high circulating IGF-I bioactivity in elderly men is associated with extended survival and with reduced cardiovascular risk

Proteolytic cleavage of insulin-like growth factor binding protein 4 (IGFBP-4). Localization of cleavage site to non-homologous region of native IGFBP-4

Insulin-like growth factor binding protein 4 (IGFBP-4) is a 24-kDa protein that binds insulin-like growth factor 1 (IGF-1) and IGF-2 with high affinity and inhibits IGF action in vitro. We recently described a protease produced by the B104 neuronal cell line that cleaves IGFBP-4, yielding an approximate 16-kDa immunoreactive protein that binds IGFs with reduced affinity. We analyzed fragments produced by exposing pure IGFBP-4 to the protease to determine potential cleavage sites. Electrospray mass spectrometry and amino acid sequencing indicated the 16-kDa fragment spanned the NH2 terminus of native IGFBP-4 through Lys-120. There was evidence for an additional proteolytic fragment beginning at amino acid 132 and continuing to the COOH terminus. Proteolysis could be blocked by a synthetic peptide that spanned amino acids 117-126 but not by peptides that contained flanking sequences 111-120 or 125-135. Mutagenesis was used to alter the basic residue at position 120. The expressed mutant IGFBP-4 (K120A) was relatively resistant to cleavage, strongly suggesting that residues 120-121 represent the cleavage site. This region of IGFBP-4 is not homologous with other IGFBPs, explaining the apparent specificity of the protease for IGFBP-4. The 16-kDa IGFBP-4 fragment no longer inhibited IGF-1-stimulated thymidine uptake in vitro, suggesting that proteolytic processing of IGFBP-4 may have important functional consequences in vivo

ETEdit v.8.1 user's manual.

This user's guide documents the capabilities and functions of the Expanded Time Phase Force Deployment Data (TPFDD) Editor (ETEdit) software application. Step-by-step procedures for using ETEdit are provided in Chapter 5. Although ETEdit is primarily an editing tool for use with various software applications, it can also be used as a stand-alone application or in tandem with another application. It provides force module data that allow you to display and modify movement requirements, as well as to display the requirement line numbers (RLNs) for both detail and parent hierarchy. The primary purpose of ETEdit is to make changes to TPFDDs. Because it has been designed as a separate application, you can apply the ETEdit capabilities for use with other models

A Silent Enzootic of an Orthopoxvirus in Ghana, West Africa: Evidence for Multi-Species Involvement in the Absence of Widespread Human Disease

Human monkeypox has never been reported in Ghana, but rodents captured in forested areas of southern Ghana were the source of the monkeypox virus introduced into the United States in 2003. Subsequent to the outbreak in the United States, 204 animals were collected from two commercial trapping sites in Ghana. Animal tissues were examined for the presence of orthopoxvirus (OPXV) DNA using a real-time polymerase chain reaction, and sera were assayed for antibodies against OPXV. Animals from five genera (Cricetomys, Graphiurus, Funiscirus, and Heliosciurus) had antibodies against OPXV, and three genera (Cricetomys, Graphiurus, and Xerus) had evidence of OPXV DNA in tissues. Additionally, 172 persons living near the trapping sites were interviewed regarding risk factors for OPXV exposure, and their sera were analyzed. Fifty-three percent had IgG against OPXV; none had IgM. Our findings suggest that several species of forest-dwelling rodents from Ghana are susceptible to naturally occurring OPXV infection, and that persons living near forests may have low-level or indirect exposure to OPXV-infected animals, possibly resulting in sub-clinical infections

Strong Magnetic Field Fluctuations within Filamentary Auroral Density Cavities Interpreted as VLF Saucer Sources

The Geoelectrodynamics and Electro-Optical Detection of Electron and SuprathermalIon Currents (GEODESIC) sounding rocket encountered more than 100 filamentary densitycavities associated with enhanced plasma waves at ELF (3 kHz) and VLF (310 kHz)frequencies and at altitudes of 800990 km during an auroral substorm. These cavities weresimilar in size (20 m diameter in most cases) to so-called lower-hybrid cavities (LHCs)observed by previous sounding rockets and satellites; however, in contrast, many of theGEODESIC cavities exhibited up to tenfold enhancements in magnetic wave powerthroughout the VLF band. GEODESIC also observed enhancements of ELF and VLFelectric fields both parallel and perpendicular to the geomagnetic field B0 within cavities,though the VLF E field increases were often not as large proportionally as seen in themagnetic fields. This behavior is opposite to that predicted by previously published theoriesof LHCs based on passive scattering of externally incident auroral hiss. We argue thatthe GEODESIC cavities are active wave generation sites capable of radiating VLF wavesinto the surrounding plasma and producing VLF saucers, with energy supplied by cold,upward flowing electron beams composing the auroral return current. This interpretation issupported by the observation that the most intense waves, both inside and outside cavities,occurred in regions where energetic electron precipitation was largely inhibited orabsent altogether. We suggest that the wave-enhanced cavities encountered by GEODESICwere qualitatively different from those observed by earlier spacecraft because of thefortuitous timing of the GEODESIC launch, which placed the payload at apogee within asubstorm-related return current during its most intense phase, lasting only a few minutes