Cosmic ray diffusion fronts in the Virgo cluster

The pair of large radio lobes in the Virgo cluster, each about 23 kpc in radius, have curiously sharp outer edges where the radio-synchrotron continuum flux declines abruptly. However, just adjacent to this sharp transition, the radio flux increases. This radio limb-brightening is observed over at least half of the perimeter of both lobes. We describe slowly propagating steady state diffusion fronts that explain these counterintuitive features. Because of the natural buoyancy of radio lobes, the magnetic field is largely tangent to the lobe boundary, an alignment that polarizes the radio emission and dramatically reduces the diffusion coefficient of relativistic electrons. As cosmic ray electrons diffuse slowly into the cluster gas, the local magnetic field and gas density are reduced as gas flows back toward the radio lobe. Radio emission peaks can occur because the synchrotron emissivity increases with magnetic field and then decreases with the density of non-thermal electrons. A detailed comparison of steady diffusion fronts with quantitative radio observations may reveal information about the spatial variation of magnetic fields and the diffusion coefficient of relativistic electrons. On larger scales, some reduction of the gas density inside the Virgo lobes due to cosmic ray pressure must occur and may be measurable. Such X-ray observations could reveal important information about the presence of otherwise unobservable non-thermal components such as relativistic electrons of low energy or proton cosmic rays.Comment: 11 pages, 5 figures, Accepted by Ap

Phenylacrylic acids addition to potato and sweet potato showed no impact on acrylamide concentration via oxa-Michael-addition during frying

Three phenolic acids, p-coumaric, ferulic and caffeic acid as well as cinnamic acid were added to raw potatoes and sweet potatoes before frying. A distinct mitigation of acrylamide was not detected. Fried samples were analysed for postulated adducts of a direct reaction between acrylamide and these phenolic acids using LC-MS. In a model system with pure compounds (phenylacrylic acid and acrylamide) heated on 10% hydrated silica gel one specific adduct (respective m/z for M ​+ ​H+) was formed in each reaction. MS/MS-data suggested an oxa-Michael formation of 3-amino-3-oxopropyl-phenylacrylates, which was confirmed by de novo syntheses along an SN2 substitution of 3-chloropropanamide. Exemplarily, the structure of the ester was confirmed for p-coumaric acid by NMR-data. Standard addition revealed that 3-amino-(3-oxopropyl-phenyl)-acrylates occurred neither in fried potato nor in sweet potato, while a formation was shown in phenylacrylic acid plus acrylamide supplemented potatoes and sweet potatoes

A Characterization of the ALMA Phasing System at 345 GHz

The development of the Atacama Large Millimeter/submillimeter Array (ALMA) phasing system (APS) has allowed ALMA to function as an extraordinarily sensitive station for very long baseline interferometry (VLBI) at frequencies of up to 230 GHz (~1.3 mm). Efforts are now underway to extend use of the APS to 345 GHz (~0.87 mm). Here we report a characterization of APS performance at 345 GHz based on a series of tests carried out between 2015-2021, including a successful global VLBI test campaign conducted in 2018 October in collaboration with the Event Horizon Telescope (EHT).Comment: 22 pages, 11 figures, 7 tables, accepted for publication in PAS

Differential var Gene Expression in Children with Malaria and Antidromic Effects on Host Gene Expression

Among 62 children with mild malaria, cerebral malaria, or severe malarial anemia, we analyzed the transcription of different var gene types. There was no difference in parasitemia level or body temperature between groups. However, a significantly different expression pattern was observed in children with cerebral malaria, compared with that in patients in the other 2 groups: children with cerebral malaria had lower expression of the upsA subtype but higher expression of the upsB and upsC subtypes. Furthermore, expression of human genes responsive to tumor necrosis factor and hypoxia correlated with distinct ups type

Zooming towards the Event Horizon - mm-VLBI today and tomorrow

Global VLBI imaging at millimeter and sub-millimeter wavelength overcomes the opacity barrier of synchrotron self-absorption in AGN and opens the direct view into sub-pc scale regions not accessible before. Since AGN variability is more pronounced at short millimeter wavelength, mm-VLBI can reveal structural changes in very early stages after outbursts. When combined with observations at longer wavelength, global 3mm and 1mm VLBI adds very detailed information. This helps to determine fundamental physical properties at the jet base, and in the vicinity of super-massive black holes at the center of AGN. Here we present new results from multi-frequency mm-VLBI imaging of OJ287 during a major outburst. We also report on a successful 1.3mm VLBI experiment with the APEX telescope in Chile. This observation sets a new record in angular resolution. It also opens the path towards future mm-VLBI with ALMA, which aims at the mapping of the black hole event horizon in nearby galaxies, and the study of the roots of jets in AGN.Comment: 6 pages, to appear in 11th European VLBI Network Symposium, ed. P. Charlot et al., Bordeaux (France), October 9-12, 201

New in vitro interaction-parasite reduction ratio assay for early derisk in clinical development of antimalarial combinations

The development and spread of drug-resistant phenotypes substantially threaten malaria control efforts. Combination therapies have the potential to minimize the risk of resistance development but require intensive preclinical studies to determine optimal combination and dosing regimens. To support the selection of new combinations, we developed a novel in vitro-in silico combination approach to help identify the pharmacodynamic interactions of the two antimalarial drugs in a combination which can be plugged into a pharmacokinetic/pharmacodynamic model built with human monotherapy parasitological data to predict the parasitological endpoints of the combination. This makes it possible to optimally select drug combinations and doses for the clinical development of antimalarials. With this assay, we successfully predicted the endpoints of two phase 2 clinical trials in patients with the artefenomel-piperaquine and artefenomel-ferroquine drug combinations. In addition, the predictive performance of our novel in vitro model was equivalent to that of the humanized mouse model outcome. Last, our more informative in vitro combination assay provided additional insights into the pharmacodynamic drug interactions compared to the in vivo systems, e.g., a concentration-dependent change in the maximum killing effect (Emax) and the concentration producing 50% of the killing maximum effect (EC50) of piperaquine or artefenomel or a directional reduction of the EC50 of ferroquine by artefenomel and a directional reduction of Emax of ferroquine by artefenomel. Overall, this novel in vitro-in silico-based technology will significantly improve and streamline the economic development of new drug combinations for malaria and potentially also in other therapeutic areas

Properties of Interfaces in the two and three dimensional Ising Model

To investigate order-order interfaces, we perform multimagnetical Monte Carlo simulations of the $2D$ and $3D$ Ising model. Following Binder we extract the interfacial free energy from the infinite volume limit of the magnetic probability density. Stringent tests of the numerical methods are performed by reproducing with high precision exact $2D$ results. In the physically more interesting $3D$ case we estimate the amplitude $F^s_0$ of the critical interfacial tension $F^s = F^s_0 t^\mu$ to be $F^s_0 = 1.52 \pm 0.05$. This result is in good agreement with a previous MC calculation by Mon, as well as with experimental results for related amplitude ratios. In addition, we study in some details the shape of the magnetic probability density for temperatures below the Curie point.Comment: 25 pages; sorry no figures include

Temporal retinal transcriptome and systems biology analysis identifies key pathways and hub genes in Staphylococcus aureus endophthalmitis

Bacterial endophthalmitis remains a devastating inflammatory condition associated with permanent vision loss. Hence, assessing the host response in this disease may provide new targets for intervention. Using a mouse model of Staphylococcus aureus (SA) endophthalmitis and performing retinal transcriptome analysis, we discovered progressive changes in the expression of 1,234 genes. Gene ontology (GO) and pathway analyses revealed the major pathways impacted in endophthalmitis includes: metabolism, inflammatory/immune, antimicrobial, cell trafficking, and lipid biosynthesis. Among the immune/inflammation pathways, JAK/Stat and IL-17A signaling were the most significantly affected. Interactive network-based analyses identified 13 focus hub genes (IL-6, IL-1β, CXCL2, STAT3, NUPR1, Jun, CSF1, CYR61, CEBPB, IGF-1, EGFR1, SPP1, and TGM2) within these important pathways. The expression of hub genes confirmed by qRT-PCR, ELISA (IL-6, IL-1β, and CXCL2), and Western blot or immunostaining (CEBP, STAT3, NUPR1, and IGF1) showed strong correlation with transcriptome data. Since TLR2 plays an important role in SA endophthalmitis, counter regulation analysis of TLR2 ligand pretreated retina or the use of retinas from TLR2 knockout mice showed the down-regulation of inflammatory regulatory genes. Collectively, our study provides, for the first time, a comprehensive analysis of the transcriptomic response and identifies key pathways regulating retinal innate responses in staphylococcal endophthalmitis

First 230 GHz VLBI Fringes on 3C 279 using the APEX Telescope

We report about a 230 GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT of the Arizona Radio Observatory (ARO). We installed VLBI equipment and measured the APEX station position to 1 cm accuracy (1 sigma). We then observed 3C 279 on 2012 May 7 in a 5 hour 230 GHz VLBI track with baseline lengths of 2800 M$\lambda$ to 7200 M$\lambda$ and a finest fringe spacing of 28.6 micro-arcseconds. Fringes were detected on all baselines with SNRs of 12 to 55 in 420 s. The correlated flux density on the longest baseline was ~0.3 Jy/beam, out of a total flux density of 19.8 Jy. Visibility data suggest an emission region <38 uas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 10^10 K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ~38 uas. With APEX the angular resolution of 230 GHz VLBI improves to 28.6 uas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40 uas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.Comment: accepted for publication in A&

Parasite viability as a measure of in vivo drug activity in preclinical and early clinical antimalarial drug assessment

The rate at which parasitemia declines in a host after treatment with an antimalarial drug is a major metric for assessment of antimalarial drug activity in preclinical models and in early clinical trials. However, this metric does not distinguish between viable and nonviable parasites. Thus, enumeration of parasites may result in underestimation of drug activity for some compounds, potentially confounding its use as a metric for assessing antimalarial activity in vivo. Here, we report a study of the effect of artesunate on Plasmodium falciparum viability in humans and in mice. We first measured the drug effect in mice by estimating the decrease in parasite viability after treatment using two independent approaches to estimate viability. We demonstrate that, as previously reported in humans, parasite viability declines much faster after artesunate treatment than does the decline in parasitemia (termed parasite clearance). We also observed that artesunate kills parasites faster at higher concentrations, which is not discernible from the traditional parasite clearance curve and that each subsequent dose of artesunate maintains its killing effect. Furthermore, based on measures of parasite viability, we could accurately predict the in vivo recrudescence of infection. Finally, using pharmacometrics modeling, we show that the apparent differences in the antimalarial activity of artesunate in mice and humans are partly explained by differences in host removal of dead parasites in the two hosts. However, these differences, along with different pharmacokinetic profiles, do not fully account for the differences in activity. (This study has been registered with the Australian New Zealand Clinical Trials Registry under identifier ACTRN12617001394336.)