Mammalian Cell Cytotoxicity Analysis of Soybean Rust Fungicides

The identification of soybean rust, caused by Phakopsora pachyrhizi H. Sydow & Sydow, in the southern United States in November 2004 (Schneider et al. 2005 ), in the Midwest in 2006 (Hartman et al. 2007 ), and elsewhere has increased the concerns of the impact of the pathogen on US soybean production (Miles et al. 2007 ). The rapid spread of P. pachyrhizi and its potential to cause severe yield losses makes this among the most destructive foliar diseases of soybean. Yield losses of 20%–60% were reported in Asia, with losses of 80% reported from experimental plots in Taiwan (Hartman et al. 1991 ). Soybean rust could have a major impact on both total soybean production and production costs in the US

Mammalian Cell Cytotoxicity Analysis of Soybean Rust Fungicides

The identification of soybean rust, caused by Phakopsora pachyrhizi H. Sydow & Sydow, in the southern United States in November 2004 (Schneider et al. 2005 ), in the Midwest in 2006 (Hartman et al. 2007 ), and elsewhere has increased the concerns of the impact of the pathogen on US soybean production (Miles et al. 2007 ). The rapid spread of P. pachyrhizi and its potential to cause severe yield losses makes this among the most destructive foliar diseases of soybean. Yield losses of 20%–60% were reported in Asia, with losses of 80% reported from experimental plots in Taiwan (Hartman et al. 1991 ). Soybean rust could have a major impact on both total soybean production and production costs in the US

Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer's disease

The epsilon4 allele of apolipoprotein E (APOE) and traumatic brain injury (TBI) are both risk factors for the development of Alzheimer's disease (AD). These factors may act synergistically, in that APOE4+ individuals are more likely to develop dementia after TBI. Because the mechanism underlying these effects is unclear, we questioned whether APOE4 and TBI interact either through effects on amyloid-beta (Abeta) or by enhancing cell death/tissue injury. We assessed the effects of TBI in PDAPP mice (transgenic mice that develop AD-like pathology) expressing human APOE3 (PDAPP:E3), human APOE4 (PDAPP:E4), or no APOE (PDAPP:E-/-). Mice were subjected to a unilateral cortical impact injury at 9-10 months of age and allowed to survive for 3 months. Abeta load, hippocampal/cortical volumes, and hippocampal CA3 cell loss were quantified using stereological methods. All of the groups contained mice with Abeta-immunoreactive deposits (56% PDAPP:E4, 20% PDAPP:E3, 75% PDAPP:E-/-), but thioflavine-S-positive Abeta (amyloid) was present only in the molecular layer of the dentate gyrus in the PDAPP:E4 mice (44%). In contrast, our previous studies showed that in the absence of TBI, PDAPP:E3 and PDAPP:E4 mice have little to no Abeta deposition at this age. After TBI, all of the Abeta deposits present in PDAPP:E3 and PDAPP:E-/- mice were diffuse plaques. In contrast to the effect of APOE4 on amyloid, PDAPP:E3, PDAPP:E4, and PDAPP:E-/- mice did not differ in the amount of brain tissue or cell loss. These data support the hypothesis that APOE4 influences the neurodegenerative cascade after TBI via an effect on Abeta

Benefit Assessment for Metroplex Tactical Runway Configuration Management (mTRCM) in a Simulated Environment

The System-Oriented Runway Management (SORM) concept is a collection of capabilities focused on a more efficient use of runways while considering all of the factors that affect runway use. Tactical Runway Configuration Management (TRCM), one of the SORM capabilities, provides runway configuration and runway usage recommendations, and monitoring the active runway configuration for suitability given existing factors. This report focuses on the metroplex environment, with two or more proximate airports having arrival and departure operations that are highly interdependent. The myriad of factors that affect metroplex opeations require consideration in arriving at runway configurations that collectively best serve the system as a whole. To assess the metroplex TRCM (mTRCM) benefit, the performance metrics must be compared with the actual historical operations. The historical configuration schedules can be viewed as the schedules produced by subject matter experts (SMEs), and therefore are referred to as the SMEs' schedules. These schedules were obtained from the FAA's Aviation System Performance Metrics (ASPM) database; this is the most representative information regarding runway configuration selection by SMEs. This report focused on a benefit assessment of total delay, transit time, and throughput efficiency (TE) benefits using the mTRCM algorithm at representative volumes for today's traffic at the New York metroplex (N90)

The Radio Sky at Meter Wavelengths: m-Mode Analysis Imaging with the Owens Valley Long Wavelength Array

A host of new low-frequency radio telescopes seek to measure the 21-cm transition of neutral hydrogen from the early universe. These telescopes have the potential to directly probe star and galaxy formation at redshifts $20 \gtrsim z \gtrsim 7$, but are limited by the dynamic range they can achieve against foreground sources of low-frequency radio emission. Consequently, there is a growing demand for modern, high-fidelity maps of the sky at frequencies below 200 MHz for use in foreground modeling and removal. We describe a new widefield imaging technique for drift-scanning interferometers, Tikhonov-regularized $m$-mode analysis imaging. This technique constructs images of the entire sky in a single synthesis imaging step with exact treatment of widefield effects. We describe how the CLEAN algorithm can be adapted to deconvolve maps generated by $m$-mode analysis imaging. We demonstrate Tikhonov-regularized $m$-mode analysis imaging using the Owens Valley Long Wavelength Array (OVRO-LWA) by generating 8 new maps of the sky north of $\delta=-30^\circ$ with 15 arcmin angular resolution, at frequencies evenly spaced between 36.528 MHz and 73.152 MHz, and $\sim$800 mJy/beam thermal noise. These maps are a 10-fold improvement in angular resolution over existing full-sky maps at comparable frequencies, which have angular resolutions $\ge 2^\circ$. Each map is constructed exclusively from interferometric observations and does not represent the globally averaged sky brightness. Future improvements will incorporate total power radiometry, improved thermal noise, and improved angular resolution -- due to the planned expansion of the OVRO-LWA to 2.6 km baselines. These maps serve as a first step on the path to the use of more sophisticated foreground filters in 21-cm cosmology incorporating the measured angular and frequency structure of all foreground contaminants.Comment: 27 pages, 18 figure

Nonhomologous end joining of complex DNA double-strand breaks with proximal thymine glycol and interplay with base excision repair

DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol at the first (Tg1), second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3' terminus, was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate base was a major barrier to end joining (>10-fold reduction in ligated products) and an absolute barrier when present at both ends. Dideoxy trapping of base excision repair intermediates indicated that Tg was excised from Tg1, Tg2 and Tg3 largely if not exclusively after DSB ligation. However, Tg was rapidly excised from the Tg5 substrate, resulting in a reduced level of DSB ligation, as well as slow concomitant resection of the opposite strand. Ligase reactions containing only purified Ku, XRCC4, ligase IV and XLF showed that ligation of Tg3 and Tg5 was efficient and only partially XLF-dependent, whereas ligation of Tg1 and Tg2 was inefficient and only detectable in the presence of XLF. Overall, the results suggest that promoting ligation of DSBs with proximal base damage may be an important function of XLF, but that Tg can still be a major impediment to repair, being relatively resistant to both trimming and ligation. Moreover, it appears that base excision repair of Tg can sometimes interfere with repair of DSBs that would otherwise be readily rejoined

Epitope Addition and Ablation via Manipulation of a Dengue Virus Serotype 1 Infectious Clone

ABSTRACT Despite the clinical relevance, dengue virus (DENV) research has been hampered by the absence of robust reverse genetic systems to manipulate the viral serotypes for propagation and generation of mutant viruses. In this article, we describe application of an infectious clone system for DENV serotype 1 (DENV1). Similar to previous clones in both flaviviruses and coronaviruses, the approach constructs a panel of contiguous cDNAs that span the DENV genome and can be systematically and directionally assembled to produce viable, full-length viruses. Comparison of the virus derived from the infectious clone with the original viral isolate reveals identical sequence, comparable endpoint titers, and similar focus staining. Both focus-forming assays and percent infection by flow cytometry revealed overlapping replication levels in two different cell types. Moreover, serotype-specific monoclonal antibodies (MAbs) bound similarly to infectious clone and the natural isolate. Using the clone, we were able to insert a DENV4 type-specific epitope recognized by primate MAb 5H2 into envelope (E) protein domain I (EDI) of DENV1 and recover a viable chimeric recombinant virus. The recombinant DENV1 virus was recognized and neutralized by the DENV4 type-specific 5H2 MAb. The introduction of the 5H2 epitope ablated two epitopes on DENV1 EDI recognized by human MAbs (1F4 and 14C10) that strongly neutralize DENV1. Together, the work demonstrates the utility of the infectious clone and provides a resource to rapidly manipulate the DENV1 serotype for generation of recombinant and mutant viruses. IMPORTANCE Dengue viruses (DENVs) are significant mosquito-transmitted pathogens that cause widespread infection and can lead to severe infection and complications. Here we further characterize a novel and robust DENV serotype 1 (DENV1) infectious clone system that can be used to support basic and applied research. We demonstrate how the system can be used to probe the antigenic relationships between strains by creating viable recombinant viruses that display or lack major antibody epitopes. The DENV1 clone system and recombinant viruses can be used to analyze existing vaccine immune responses and inform second-generation bivalent vaccine designs

The Advanced Compton Telescope

The Advanced Compton Telescope (ACT), the next major step in gamma-ray astronomy, will probe the fires where chemical elements are formed by enabling high-resolution spectroscopy of nuclear emission from supernova explosions. During the past two years, our collaboration has been undertaking a NASA mission concept study for ACT. This study was designed to (1) transform the key scientific objectives into specific instrument requirements, (2) to identify the most promising technologies to meet those requirements, and (3) to design a viable mission concept for this instrument. We present the results of this study, including scientific goals and expected performance, mission design, and technology recommendations

International Space Station Spacecraft Charging Environments: Modeling, Measurement and Implications for Future Human Space Flight Programs

Spacecraft charging analysis and migration is an interdisciplinary subject combining aspects of electrostatics, plasma physics, ionizing radiation, and materials science, as well as electronic system electromagnetic interference and compatibility (EMI/EMC) effects. Spacecraft charging hazards are caused by the accumulation of electrical charge on spacecraft and spacecraft components produced by interactions with space plasmas, energetic charged particles, and solar UV photons as well as spacecraft electrical power and propulsion systems operations. Spacecraft charging hazard effects include both hard and soft avionics and electrical power system anomalies and have led to the partial or complete loss of numerous spacecraft. The International Space Station (ISS) orbital altitude and inclination (~400 km and 51.6o) determined the dominant natural environment factors affecting ISS spacecraft charging; high speed flight through the geomagnetic field and electrical power system interaction with the cold, high-density ionospheric plasma. In addition ISS is exposed to energetic auroral electrons at high latitude. In this paper we present the results of ISS spacecraft charging modeling and measurements and compare the measurements with numerical modeling of ISS charging processes. ISS is a large metallic structure and flight through the geomagnetic field at orbital speed dominates ISS charging. Collection of ionospheric electrons by the large 160V PV arrays is the next largest contributor. Charging by auroral electrons is detectable but makes a relatively minor contribution. Finally we report the observation of short duration (~ 1 sec) rapid charging peaks associated with shunt/un-shunt operations of the 160V PV arrays, a phenomena not predicted before flight. ISS spacecraft charging environments are radically different from those encountered at higher altitudes in Earth?s magnetosphere and in cis-Lunar space. We present a brief review of those charging environments and an assessment of the applicability of ISS spacecraft charging management and experience to future human spaceflight programs beyond LEO