Triggering Collapse of the Presolar Dense Cloud Core and Injecting Short-Lived Radioisotopes with a Shock Wave. IV. Effects of Rotational Axis Orientation

Both astronomical observations of the interaction of Type II supernova remnants (SNR) with dense interstellar clouds as well as cosmochemical studies of the abundances of daughter products of short-lived radioisotopes (SLRIs) formed by supernova nucleosynthesis support the hypothesis that the Solar Systems SLRIs may have been derived from a supernova. This paper continues a series devoted to examining whether such a shock wave could have triggered the dynamical collapse of a dense, presolar cloud core and simultaneously injected sufficient abundances of SLRIs to explain the cosmochemical evidence. Here we examine the effects of shock waves striking clouds whose spin axes are oriented perpendicular, rather than parallel, to the direction of propagation of the shock front. The models start with 2.2 solar mass cloud cores and shock speeds of 20 or 40 km/sec. Central protostars and protoplanetary disks form in all models, though with disk spin axes aligned somewhat randomly. The disks derive most of their angular momentum not from the initial cloud rotation, but from the Rayleigh-Taylor fingers that also inject shock wave SLRIs. Injection efficiencies, fi, the fraction of the incident shock wave material injected into the collapsing cloud core, are 0.04 - 0.1 in these models, similar to when the rotation axis is parallel to the shock propagation direction. Evidently altering the rotation axis orientation has only a minor effect on the outcome, strengthening the case for this scenario as an explanation for the Solar Systems SLRIs.Comment: 24 pages, 12 figures, 1 table, accepted by Ap

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia

Drycore Appears to Result from an Interaction between Rhizoctonia solani and Wireworm ( Agriotes ssp.)—Evidence from a 3-Year Field Survey

Drycore is an important quality deficiency in Europe especially in organic potato production and after grass clover leys. The drycore symptom is attributed to Rhizoctonia solani Kühn (teleomorph: Thanatephorus cucumeris (Frank) Donk). In the framework of a 3-year survey (2001-2003), data concerning potato quality, crop rotation, management, and site parameters were analysed from 185 potato fields. The hypothesis was tested that injuries on potatoes caused by wireworms facilitate the penetration of R. solani and favour the formation of drycore. Analysis of variance showed a significant influence of wireworm damage, seed quality, and grass clover leys in the crop on the level of drycore damage. On fields which had both a low occurrence of black scurf on the seed tubers and a low occurrence of wireworm damage at harvest, significant drycore damage was never observed. The relative risk for drycore damage on tubers was significantly higher if black scurf or wireworm damage was on the same tuber. In contrast, no higher risk for drycore was observed on tubers with slug damage. Abiotic factors like farm manure application, organic matter content, texture, and pH of the soil also had no significant influence on the level of drycore. Thus, the wounding of potatoes by wireworm could be confirmed as the major variable for drycore. The mode of action has to be clarified under controlled condition

Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16μg/ml and 0.05μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50=0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191mg/kg and 147mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrin

Simultaneous Triggered Collapse of the Presolar Dense Cloud Core and Injection of Short-Lived Radioisotopes by a Supernova Shock Wave

Cosmochemical evidence for the existence of short-lived radioisotopes (SLRI) such as $^{26}$Al and $^{60}$Fe at the time of the formation of primitive meteorites requires that these isotopes were synthesized in a massive star and then incorporated into chondrites within $\sim 10^6$ yr. A supernova shock wave has long been hypothesized to have transported the SLRI to the presolar dense cloud core, triggered cloud collapse, and injected the isotopes. Previous numerical calculations have shown that this scenario is plausible when the shock wave and dense cloud core are assumed to be isothermal at $\sim 10$ K, but not when compressional heating to $\sim 1000$ K is assumed. We show here for the first time that when calculated with the FLASH2.5 adaptive mesh refinement (AMR) hydrodynamics code, a 20 km/sec shock wave can indeed trigger the collapse of a 1 $M_\odot$ cloud while simultaneously injecting shock wave isotopes into the collapsing cloud, provided that cooling by molecular species such as H$_2$O, CO$_2$, and H$_2$ is included. These calculations imply that the supernova trigger hypothesis is the most likely mechanism for delivering the SLRI present during the formation of the solar system.Comment: 12 pages, 4 color figures. Astrophysical Journal Letters (in press