Characteristics of Low-Latitude Coronal Holes near the Maximum of Solar cycle 24

We investigate the statistics of 288 low-latitude coronal holes extracted from SDO/AIA-193 filtergrams over the time range 2011/01/01 to 2013/12/31. We analyse the distribution of characteristic coronal hole properties, such as the areas, mean AIA-193 intensities, and mean magnetic field densities, the local distribution of the SDO/AIA-193 intensity and the magnetic field within the coronal holes, and the distribution of magnetic flux tubes in coronal holes. We find that the mean magnetic field density of all coronal holes under study is 3.0 +- 1.6 G, and the percentage of unbalanced magnetic flux is 49 +- 16 %. The mean magnetic field density, the mean unsigned magnetic field density, and the percentage of unbalanced magnetic flux of coronal holes depend strongly pairwise on each other, with correlation coefficients cc > 0.92. Furthermore, we find that the unbalanced magnetic flux of the coronal holes is predominantly concentrated in magnetic flux tubes: 38 % (81 %) of the unbalanced magnetic flux of coronal holes arises from only 1 % (10 %) of the coronal hole area, clustered in magnetic flux tubes with field strengths > 50 G (10 G). The average magnetic field density and the unbalanced magnetic flux derived from the magnetic flux tubes correlate with the mean magnetic field density and the unbalanced magnetic flux of the overall coronal hole (cc > 0.93). These findings give evidence that the overall magnetic characteristics of coronal holes are governed by the characteristics of the magnetic flux tubes.Comment: 15 figure

Review of Experimental Compounds Demonstrating Anti-Toxoplasma Activity

Toxoplasma gondii is a ubiquitous apicomplexan parasite capable of infecting humans and other animals. Current treatment options for T. gondii infection are limited and most have drawbacks, including high toxicity and low tolerability. Additionally, no FDA-approved treatments are available for pregnant women, a high-risk population due to transplacental infection. Therefore, the development of novel treatment options is needed. To aid this effort, this review highlights experimental compounds that, at a minimum, demonstrate inhibition of in vitro growth of T. gondii. When available, host cell toxicity and in vivo data are also discussed. The purpose of this review is to facilitate additional development of anti-Toxoplasma compounds and potentially to extend our knowledge of the parasite

Clinically Available Medicines Demonstrating Anti-\u3ci\u3eToxoplasma\u3c/i\u3e Activity

Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts

How the area of solar coronal holes affects the properties of high-speed solar wind streams near Earth : An analytical model

Since the 1970s it has been empirically known that the area of solar coronal holes affects the properties of high-speed solar wind streams (HSSs) at Earth. We derive a simple analytical model for the propagation of HSSs from the Sun to Earth and thereby show how the area of coronal holes and the size of their boundary regions affect the HSS velocity, temperature, and density near Earth. We assume that velocity, temperature, and density profiles form across the HSS cross section close to the Sun and that these spatial profiles translate into corresponding temporal profiles in a given radial direction due to the solar rotation. These temporal distributions drive the stream interface to the preceding slow solar wind plasma and disperse with distance from the Sun. The HSS properties at 1 AU are then given by all HSS plasma parcels launched from the Sun that did not run into the stream interface at Earth distance. We show that the velocity plateau region of HSSs as seen at 1 AU, if apparent, originates from the center region of the HSS close to the Sun, whereas the velocity tail at 1 AU originates from the trailing boundary region. Small HSSs can be described to entirely consist of boundary region plasma, which intrinsically results in smaller peak velocities. The peak velocity of HSSs at Earth further depends on the longitudinal width of the HSS close to the Sun. The shorter the longitudinal width of an HSS close to the Sun, the more of its "fastest" HSS plasma parcels from the HSS core and trailing boundary region have impinged upon the stream interface with the preceding slow solar wind, and the smaller is the peak velocity of the HSS at Earth. As the longitudinal width is statistically correlated to the area of coronal holes, this also explains the well-known empirical relationship between coronal hole areas and HSS peak velocities. Further, the temperature and density of HSS plasma parcels at Earth depend on their radial expansion from the Sun to Earth. The radial expansion is determined by the velocity gradient across the HSS boundary region close to the Sun and gives the velocity-temperature and density-temperature relationships at Earth their specific shape. When considering a large number of HSSs, the assumed correlation between the HSS velocities and temperatures close to the Sun degrades only slightly up to 1 AU, but the correlation between the velocities and densities is strongly disrupted up to 1 AU due to the radial expansion. Finally, we show how the number of particles of the piled-up slow solar wind in the stream interaction region depends on the velocities and densities of the HSS and preceding slow solar wind plasma.Peer reviewe

Methyl-Substituted Dispiro-1,2,4,5-tetraoxanes: Correlations of Structural Studies with Antimalarial Activity

Two tetramethyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15,16-tetraoxadispiro[5.2.5.2]- hexadecanes) 3 and 4 were designed as metabolically stable analogues of the dimethylsubstituted dispiro-1,2,4,5-tetraoxane prototype WR 148999 (2). For a positive control we selected the sterically unhindered tetraoxane 5 (7,8,15,16-tetraoxadispiro[5.2.5.2]hexadecane), devoid of any substituents. Tetraoxanes 3 and 4 were completely inactive in contrast to tetraoxanes 2 and 5. We hypothesize that the two inactive tetraoxanes possess sufficient steric hindrance about the tetraoxane ring due to the two additional axial methyl groups to prevent their activation to presumed parasiticidal carbon radicals by inhibiting electron transfer from heme or other iron(II) species. For each of the tetraoxanes 2-4, the tetraoxane and both spirocyclohexyl rings are in a chair conformation and the bond lengths and angles are all quite normal except for the C1-C2 bond which is slightly lengthened. Comparison of the modeled and X-ray structures for tetraoxanes 2-5 reveals that molecular mechanics (MMX and MM3) and 3-21G* calculations each gave accurate structural parameters such as bond lengths, bond angles, and dihedral angles. In contrast, semiempirical methods such as AM1 gave poor results

Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513.

BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing\u27s Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 10(6) BE (2)-c cells followed by immediate treatment with 50-100 mg/kg/day doses of OZ513 administered IP three times per week out to 23 days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N = 6), and OZ513 treated mice (N = 5). RESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth. CONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear

Earth-Affecting Solar Causes Observatory (EASCO): A mission at the Sun-Earth L5

Coronal mass ejections (CMEs) and corotating interaction regions (CIRs) as well as their source regions are important because of their space weather consequences. The current understanding of CMEs primarily comes from the Solar and Heliospheric Observatory (SOHO) and the Solar Terrestrial Relations Observatory (STEREO) missions, but these missions lacked some key measurements: STEREO did not have a magnetograph; SOHO did not have in-situ magnetometer. SOHO and other imagers such as the Solar Mass Ejection Imager (SMEI) located on the Sun-Earth line are also not well-suited to measure Earth-directed CMEs. The Earth-Affecting Solar Causes Observatory (EASCO) is a proposed mission to be located at the Sun-Earth L5 that overcomes these deficiencies. The mission concept was recently studied at the Mission Design Laboratory (MDL), NASA Goddard Space Flight Center, to see how the mission can be implemented. The study found that the scientific payload (seven remote-sensing and three in-situ instruments) can be readily accommodated and can be launched using an intermediate size vehicle; a hybrid propulsion system consisting of a Xenon ion thruster and hydrazine has been found to be adequate to place the payload at L5. Following a 2-year transfer time, a 4-year operation is considered around the next solar maximum in 2025.Comment: 12 pages, 6 figures, 2 table

Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513.

BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing\u27s Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 10(6) BE (2)-c cells followed by immediate treatment with 50-100 mg/kg/day doses of OZ513 administered IP three times per week out to 23 days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N = 6), and OZ513 treated mice (N = 5). RESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth. CONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear

Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl hydrazone (KG8) as the most promising compound; KG8 displayed potent in vitro activity against T. gondii but only marginal in vivoefficacy in a T. gondii animal model. To define the potential of this new lead compound, we now describe a baseline structure-activity relationship for this chemotype. Several derivatives displayed IC50\u27s comparable to that of the control treatment pyrimethamine with little to no cytotoxicity. The best of these, KGW44 and KGW59, had higher metabolic stability than KG8. In an in vivo T. gondii murine model, KGW59 significantly increased survivorship. This work provides new insights for optimization of this novel chemotype