Nitroheterocyclic drug resistance mechanisms in <i>Trypanosoma brucei</i>

OBJECTIVES: The objective of this study was to identify the mechanisms of resistance to nifurtimox and fexinidazole in African trypanosomes. METHODS: Bloodstream-form Trypanosoma brucei were selected for resistance to nifurtimox and fexinidazole by stepwise exposure to increasing drug concentrations. Clones were subjected to WGS to identify putative resistance genes. Transgenic parasites modulating expression of genes of interest were generated and drug susceptibility phenotypes determined. RESULTS: Nifurtimox-resistant (NfxR) and fexinidazole-resistant (FxR) parasites shared reciprocal cross-resistance suggestive of a common mechanism of action. Previously, a type I nitroreductase (NTR) has been implicated in nitro drug activation. WGS of resistant clones revealed that NfxR parasites had lost >100 kb from one copy of chromosome 7, rendering them hemizygous for NTR as well as over 30 other genes. FxR parasites retained both copies of NTR, but lost >70 kb downstream of one NTR allele, decreasing NTR transcription by half. A single knockout line of NTR displayed 1.6- and 1.9-fold resistance to nifurtimox and fexinidazole, respectively. Since NfxR and FxR parasites are ∼6- and 20-fold resistant to nifurtimox and fexinidazole, respectively, additional factors must be involved. Overexpression and knockout studies ruled out a role for a putative oxidoreductase (Tb927.7.7410) and a hypothetical gene (Tb927.1.1050), previously identified in a genome-scale RNAi screen. CONCLUSIONS: NTR was confirmed as a key resistance determinant, either by loss of one gene copy or loss of gene expression. Further work is required to identify which of the many dozens of SNPs identified in the drug-resistant cell lines contribute to the overall resistance phenotype

Multi-band Multi-site GNSS RFI Monitoring Results after a Year of Operation

An international network of Radio Frequency Interference (RFI) monitoring stations covering all L-band Global Navigation Satellite System (GNSS) signals has provided large amounts of data on the occurrence rates and characteristics of the detected sources. As the stations are primarily deployed by roadways the measurements include a large number of Personal Privacy Device (PPD) style jammers as well as an unexpectedly large contingent of spurious emissions and co-authorized users. Important results include the high levels of variability in month-to-month activity levels of sites indicating that site survey activities must be conducted over longer periods to obtain accurate occurrence rate information.acceptedVersio

Characterization of the GNSS RFI Threat to DFMC GBAS Signal Bands

This article presents analysis results from a long-term multi-site Global Navigation Satellite System (GNSS) Radio Frequency Interference (RFI) monitoring campaign in the context of Ground Based Augmentation System (GBAS) Dual Frequency Multi Constellation (DFMC) concept operation. GBAS resilience against unintentional RFI is an important area for investigation as the ground station receivers often must operate adjacent to high-traffic roads where chances of being affected by RFI are high. To be able to develop algorithms and reaction strategies necessary to ensure continuity and availability of service, knowledge of interference signal characteristics and frequency band/bands affected, as well as relative occurrence rates between the considered frequencies and frequency combinations, is necessary. The analysis presented in the article covers the prevalence and properties of the RFI events observed on the GPS L1 and L5 and the Galileo E1 and E5a frequency bands that are considered by the on-going DFMC GBAS concept development initiatives. Due to being spectrally adjacent, the observed event analysis is also carried out for the Galileo E5b and GLONASS G1 frequency bands. The article also addresses the issue of spectral occupancy distribution of the observed events and presents new interesting RFI event types captured during the considered monitoring period.publishedVersio

Automatic GNSS RFI Classification Challenges

This article describes the real-world challenges that are encountered when trying to automatically categorize and classify the radio frequency interference (RFI) events captured in the GNSS signal bands by an international network of monitoring stations covering all L-band navigation signals. While signals frequently fall into the often-discussed categories such as 'chirp', 'continuous wave', or 'wideband noise', there is a large and growing number of modulations encountered in reality, both intentional and unintentional. These bear varying degrees of resemblance to the aforementioned traditional categories. Work presented herein focuses on some of the main complications encountered when categorizing multiple years of GNSS RFI event data, and the algorithmic approaches used to proceed with classification in these conditions.publishedVersio

Vacuum polarization alters the spectra of accreting X-ray pulsars

It is a common belief that for magnetic fields typical for accreting neutron stars in High-Mass X-ray Binaries vacuum polarization only affects the propagation of polarized emission in the neutron star magnetosphere. We show that vacuum resonances can significantly alter the emission from the poles of accreting neutron stars. The effect is similar to vacuum polarization in the atmospheres of isolated neutron stars and can result in suppression of the continuum and the cyclotron lines. It is enhanced by magnetic Comptonization in the hot plasma and proximity to the electron cyclotron resonance. We present several models to illustrate the vacuum polarization effect for various optically thick media and discuss how the choice of polarization modes affects the properties of the emergent radiation by simulating polarized energy- and angle-dependent radiative transfer. Polarization effects, including vacuum polarization, crucially alter the emission properties. Together with strongly angle- and energy- dependent magnetic Comptonization, they result in a complex spectral shape, which can be described by dips and humps on top of a power-law-like continuum with high-energy cutoff. These effects provide a possible explanation for the common necessity of additional broad Gaussian components and two-component Comptonization models that are used to describe spectra of accreting X-ray pulsars. We also demonstrate the character of depolarization introduced by the radiation field's propagation inside the inhomogeneous emission region.Comment: 4 pages, 6 figures, accepted for publication in A&A Letter

Differential ZTD estimation based on high spatial resolution NWP data for the Nordic countries

This paper contains results from a study where Numerical Weather Product (NWP) data provided by MET Norway are used to estimate the differential zenith tropospheric delay (dZTD) for an area covering Scandinavia, Finland and the Baltic countries. The NWP data have a high spatial resolution of 2.5 × 2.5 km, and the estimated dZTD for the grid positions allow for calculation of the tropospheric gradient on short baselines. The results give an indication of how large dZTD values that can be observed for baselines up to 20 km, and where the largest events are located within the coverage area. The motivation for this investigation is to better understand the characteristics of this phenomena and how it might impact high precision and/or high integrity GNSS-based navigation systems in these regions.acceptedVersio

Dynamics of PDMS- g-PDMS Bottlebrush Polymers by Broadband Dielectric Spectroscopy

Copyright © 2020 American Chemical Society. Poly(dimethylsiloxane) (PDMS)-based bottlebrush polymers, PDMS-g-PDMS, have been synthesized by anionic polymerization in combination with a condensation-based grafting reaction. Bottlebrush polymers show intriguing features, e.g., extremely low viscosities. Hereby, studies of their dynamics are rare. Therefore, we focus on the segmental relaxation by broadband dielectric spectroscopy. An increasing cross-sectional radius proportional to the increasing side chain length has been observed by small-angle neutron scattering over three samples. A comparison of the segmental relaxation times of the bottlebrushes with the respective linear chains reveals slower dynamics in the former. For longer chains, this effect vanishes

Hydrodynamic modelling of the microbial water quality in a drinking water source as input for risk reduction management

To mitigate the faecal contamination of drinking water sources and, consequently, to prevent waterborne disease outbreaks, an estimation of the contribution from different sources to the total faecal contamination at the raw water intake of a drinking water treatment plant is needed. The aim of this article was to estimate how much different sources contributed to the faecal contamination at the water intake in a drinking water source, Lake Rådasjön in Sweden. For this purpose, the fate and transport of faecal indicator Escherichia coli within Lake Rådasjön were simulated by a three-dimensional hydrodynamic model. The calibrated hydrodynamic model described the measured data on vertical temperature distribution in the lake well (the Pearson correlation coefficient was 0.99). The data on the E. coli load from the identified contamination sources were gathered and the fate and transport of E. coli released from these sources within the lake were simulated using the developed hydrodynamic model, taking the decay of the E. coli into account. The obtained modelling results were compared to the observed E. coli concentrations at the water intake. The results illustrated that the sources that contributed the most to the faecal contamination at the water intake in Lake Rådasjön were the discharges from the on-site sewers and the main inflow to the lake – the river Mölndalsån. Based on the modelling results recommendations for water producers were formulated. The study demonstrated that this modelling approach is a useful tool for estimating the contribution from different sources to the faecal contamination at the water intake of a drinking water treatment plant and provided decision-support information for the reduction of risks posed to the drinking water source

GNSS-Denied Navigation using Direction of Arrival from Low-Cost Software Defined Radios and Signals of Opportunity

This paper describes a novel navigation system for outdoor navigation in conditions where reliable satellite navigation cannot be assumed. It is build around inexpensive of-the-shelf hardware and could be used with several different signal types, allowing flexibility in usage. The system is currently in a proof-of-concept stage, and this paper shows that there are promising preliminary results.acceptedVersio

The earliest spectroscopy of the GRB 030329 afterglow with 6-m telescope

The earliest BTA (SAO RAS 6-m telescope) spectroscopic observations of the GRB 030329 optical transient (OT) are presented, which almost coincide in time with the "first break" ($t\sim 0.5$ day after the GRB) of the OT light curve. The beginning of spectral changes are seen as early as $\sim 10-12$ hours after the GRB. So, the onset of the spectral changes for $t<1$ day indicates that the contribution from Type Ic supernova (SN) into the OT optical flux can be detected earlier. The properties of early spectra of GRB 030329/SN 2003dh can be consistent with a shock moving into a stellar wind formed from the pre-SN. Such a behavior (similar to that near the UV shock breakout in SNe) can be explained by the existence of a dense matter in the immediate surroundings of massive stellar GRB/SN progenitor). The urgency is emphasized of observation of early GRB/SN spectra for solving a question that is essential for understanding GRB physical mechanism: {\it Do all} long-duration gamma-ray bursts are caused by (or physically connected to) {\it ordinary} core-collapse supernovae? If clear association of normal/ordinary core-collapse SNe (SN Ib/c, and others SN types) and GRBs would be revealed in numbers of cases, we may have strong observational limits for gamma-ray beaming and for real energetics of the GRB sources.Comment: 4 pages, 5 figures. Proceedings of the 4th Workshop "Gamma-Ray Bursts in the Afterglow Era", Roma, 2004 October 18-22, eds. L. Piro, L. Amati, S. Covino, and B. Gendre. Il Nuovo Cimento, in pres