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

Ionospheric Currents and F-Region Plasma Boundaries Near the Dayside Cusp

Observational evidence of the location of a dayside high‐latitude ionospheric current (DPY current) with respect to the different regimes of the high‐latitude magnetosphere is obtained by analyzing data from the magnetometer chain along the west coast of Greenland in conjunction with simultaneous measurements from the newly established incoherent‐scatter radar facility at Sondre Stromfjord. The latitudinal location of the DPY current is compared with the location of the maximum F‐region electron temperature and with the location of the plasma convection reversal from sunward to antisunward. The maximum in the F‐region electron temperature roughly coincides with the velocity reversal boundary, while the DPY current is always located more poleward, penetrating deep into the polar cap. When UT variations are examined, a correlation of 70 to 80 percent is found between the three locations

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

Observations of Interplanetary Magnetic Field and of Ionospheric Plasma Convection in the Vicinity of the Dayside Polar Cleft

Dayside ionospheric convection at high latitudes has been examined during a series of experiments using the Sondrestrom radar together with ancillary observations of the interplanetary magnetic field (IMF) by the IMP‐8 spacecraft. The radar experiments obtained a latitude coverage of 67.6° Λ to 81.30° Λ and a temporal resolution of between 14 to 25 minutes. A total of 17 rotations through the dayside cleft region during April, June and July, 1983 have been examined. The observations show two convection cells with sunward flow at lower latitudes and antisunward flow at higher latitudes. The flow commonly rotates through a 180° angle resulting in the predominant appearance of east‐west flows. Rapid temporal variations in the convection velocities are frequently observed. Many of the high latitude variations in convection velocity appear to be directly related to variations in the IMF By component, with eastward (westward) velocity associated with negative (positive) By . This is strong evidence for a direct electrical coupling between the solar wind and dayside high latitude ionosphere

Climatology of the Auroral Electrojets Derived From the Along-Track Gradient of Magnetic Field Intensity Measured by POGO, Magsat, CHAMP, and Swarm

The auroral electrojets (AEJs) are complex and dynamic horizontal ionospheric electric currents which form ovals around Earth’s poles, being controlled by the morphology of the main magnetic field and the energy input from the solar wind interaction with the magnetosphere. The strength and location of the AEJ varies with solar wind conditions and the solar cycle but should also be controlled on decadal timescales by main field secular variation. To determine the AEJ climatology, we use data from four polar Low Earth Orbit magnetic satellite missions: POGO, Magsat, CHAMP, and Swarm. A simple estimation of the AEJ strength and latitude is made from each pass of the satellites, from peaks in the along-track gradient of the magnetic field intensity after subtracting a core and crustal magnetic field model. This measure of the AEJ activity is used to study the response in different sectors of magnetic local time (MLT) during different seasons and directions of the interplanetary magnetic field (IMF). We find a season-dependent hemispherical asymmetry in the AEJ response to IMF By, with a tendency toward stronger (weaker) AEJ currents in the north than the south during By>0 (By<0) around local winter. This effect disappears during local summer when we find a tendency toward stronger currents in the south than the north. The solar cycle modulation of the AEJ and the long-term shifting of its position and strength due to the core field variation are presented as challenges to internal field modelling

Isothermal Microcalorimetry, a New Tool to Monitor Drug Action against Trypanosoma brucei and Plasmodium falciparum

Isothermal microcalorimetry is an established tool to measure heat flow of physical, chemical or biological processes. The metabolism of viable cells produces heat, and if sufficient cells are present, their heat production can be assessed by this method. In this study, we investigated the heat flow of two medically important protozoans, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Heat flow signals obtained for these pathogens allowed us to monitor parasite growth on a real-time basis as the signals correlated with the number of viable cells. To showcase the potential of microcalorimetry for measuring drug action on pathogenic organisms, we tested the method with three antitrypanosomal drugs, melarsoprol, suramin and pentamidine and three antiplasmodial drugs, chloroquine, artemether and dihydroartemisinin, each at two concentrations on the respective parasite. With the real time measurement, inhibition was observed immediately by a reduced heat flow compared to that in untreated control samples. The onset of drug action, the degree of inhibition and the time to death of the parasite culture could conveniently be monitored over several days. Microcalorimetry is a valuable element to be added to the toolbox for drug discovery for protozoal diseases such as human African trypanosomiasis and malaria. The method could probably be adapted to other protozoan parasites, especially those growing extracellularly

Forecasting the space weather impact: The COMESEP project

The FP7 COronal Mass Ejections and Solar Energetic Particles (COMESEP) project is developing tools for forecasting geomagnetic storms and solar energetic particle (SEP) radiation storms. By analysis of historical data, complemented by the extensive data coverage of solar cycle 23, the key ingredients that lead to magnetic storm and SEP events and the factors that are responsible for false alarms are being identified. To enhance our understanding of the 3-D kinematics and interplanetary propagation of coronal mass ejections (CMEs), the structure, propagation and evolution of CMEs are being investigated. In parallel, the sources and propagation of SEPs are being examined and modelled. COMESEP is a unique cross-collaboration effort and bridges the gap between the SEP, CME and terrestrial effects scientific communities

Influence of LAR and VAR on Para-Aminopyridine Antimalarials Targetting Haematin in Chloroquine-Resistance

Antimalarial chloroquine (CQ) prevents haematin detoxication when CQ-base concentrates in the acidic digestive vacuole through protonation of its p-aminopyridine (pAP) basic aro- matic nitrogen and sidechain diethyl-N. CQ export through the variant vacuolar membrane export channel, PFCRT, causes CQ-resistance in Plasmodium falciparum but 3-methyl CQ (sontochin SC), des-ethyl amodiaquine (DAQ) and bis 4-aminoquinoline piperaquine (PQ) are still active. This is determined by changes in drug accumulation ratios in parasite lipid (LAR) and in vacuolar water (VAR). Higher LAR may facilitate drug binding to and blocking PFCRT and also aid haematin in lipid to bind drug. LAR for CQ is only 8.3; VAR is 143,482. More hydrophobic SC has LAR 143; VAR remains 68,523. Similarly DAQ with a phenol sub- stituent has LAR of 40.8, with VAR 89,366. In PQ, basicity of each pAP is reduced by distal piperazine N, allowing very high LAR of 973,492, retaining VAR of 104,378. In another bis quinoline, dichlorquinazine (DCQ), also active but clinically unsatisfactory, each pAP retains basicity, being insulated by a 2-carbon chain from a proximal nitrogen of the single linking piperazine. While LAR of 15,488 is still high, the lowest estimate of VAR approaches 4.9 million. DCQ may be expected to be very highly lysosomotropic and therefore potentially hepatotoxic. In 11 pAP antimalarials a quadratic relationship between logLAR and logRe- sistance Index (RI) was confirmed, while log (LAR/VAR) vs logRI for 12 was linear. Both might be used to predict the utility of structural modifications

Microcalorimetry and spectroscopic studies on the binding of dye janus green blue to deoxyribonucleic acid

The interaction of the phenazinium dye janus green blue (JGB) with deoxyribonucleic acid was investigated using isothermal titration calorimetry and thermal melting experiments. The calorimetric data were supplemented by spectroscopic studies. Calorimetry results suggested the binding affinity of the dye to DNA to be of the order of 105 M-1. The binding was predominantly entropy driven with a small negative favorable enthalpy contribution to the standard molar Gibbs energy change.The binding became weaker as the temperature and salt concentration was raised. The temperature dependence of the standard molar enthalpy changes yielded negative values of standard molar heat capacity change for the complexation revealing substantial hydrophobic contribution in the DNA binding. An enthalpy–entropy compensation behavior was also observed in the system. The salt dependence of the binding yielded the release of 0.69 number of cations on binding of each dye molecule. The non-polyelectrolytic contribution was found to be the predominant force in the binding interaction. Thermal melting studies revealed that the DNA helix was stabilized against denaturation by the dye. The binding was also characterized by absorbance, resonance light scattering and circular dichroism spectral measurements. The binding constants from the spectral results were close to those obtained from the calorimetric data. The energetic aspects of the interaction of the dye JGB to double stranded DNA are supported by strong binding revealed from the spectral data

Advancing Drug Innovation for Neglected Diseases—Criteria for Lead Progression

The current drug R&D pipeline for most neglected diseases remains weak, and unlikely to support registration of novel drug classes that meet desired target product profiles in the short term. This calls for sustained investment as well as greater emphasis in the risky upstream drug discovery. Access to technologies, resources, and strong management as well as clear compound progression criteria are factors in the successful implementation of any collaborative drug discovery effort. We discuss how some of these factors have impacted drug discovery for tropical diseases within the past four decades, and highlight new opportunities and challenges through the virtual North–South drug discovery network as well as the rationale for greater participation of institutions in developing countries in product innovation. A set of criteria designed to facilitate compound progression from screening hits to drug candidate selection is presented to guide ongoing efforts