A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1- biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+and CD4+T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Metallothionein, Copper and Zinc in Fetal and Neonatal Human Liver: Changes During Development.

Total and cytosolic zinc (Zn) and copper (Cu), cytosolic metallothionein (MT) and the Cu-load of MT were investigated in fetal (22, 24 and 32 gestational weeks) and neonatal (2-15 months) human liver. Whereas the fraction of cytosolic Zn remained constant at 66% of the total independent of the stage of development, the fraction of cytosolic Cu increased from 26% in preterm liver to about 100% within 12 months postnatally. The MT content was higher in fetal than in neonatal liver. There was a linear correlation (r = 0.996) between cytosolic MT and Zn in both fetal and neonatal liver but not between MT and Cu. In contrast to fetal liver, the Cu-load of MT in neonatal liver seems to be determined by the Zn/Cu ratio in the cytosol. The results suggest that MT is involved in the regulation of Cu and Zn metabolism during fetal and neonatal development

Soil bioretention protects juvenile salmon and their prey from the toxic impacts of urban stormwater runoff

•Characterized the chemistry and toxicity of highway runoff from six storm events.•Highway runoff caused lethal and sublethal toxicity in juvenile salmon and their prey.•We treated highway runoff via infiltration through a bioretention soil media (BSM).•BSM was 60% sand: 15% compost: 15% shredded bark: 10% water treatment residuals.•Bioretention treatment of runoff prevented all mortality and sublethal toxicity. Green stormwater infrastructure (GSI), or low impact development, encompasses a diverse and expanding portfolio of strategies to reduce the impacts of stormwater runoff on natural systems. Benchmarks for GSI success are usually framed in terms of hydrology and water chemistry, with reduced flow and loadings of toxic chemical contaminants as primary metrics. Despite the central goal of protecting aquatic species abundance and diversity, the effectiveness of GSI treatments in maintaining diverse assemblages of sensitive aquatic taxa has not been widely evaluated. In the present study we characterized the baseline toxicity of untreated urban runoff from a highway in Seattle, WA, across six storm events. For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia, causing up to 100% mortality or impairing reproduction among survivors. We then evaluated whether soil media used in bioretention, a conventional GSI method, could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch) as well as their macroinvertebrate prey, including cultured C. dubia and wild-collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally lethal to salmon and invertebrates, and this acute mortality was eliminated when the runoff was filtered through soil media in bioretention columns. Soil treatment also protected against sublethal reproductive toxicity in C. dubia. Thus, a relatively inexpensive GSI technology can be highly effective at reversing the acutely lethal and sublethal effects of urban runoff on multiple aquatic species

Transverse and longitudinal multi-bunch feedback systems for PETRA

Available from TIB Hannover: RA 2999(91-036) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Gut metabolites and bacterial community networks during a pilot intervention study with flaxseeds in healthy adult men.

SCOPE: Flaxseeds contain the phytoestrogens lignans that must be activated to enterolignans by intestinal bacteria. We investigated the impact of flaxseeds on fecal bacterial communities and their associations with fecal and blood metabolites. METHODS AND RESULTS: Nine healthy male adult subjects ingested 0.3 g/kg/d flaxseeds during one week. Gut bacteria as well as blood and fecal metabolites were analyzed. Ingestion of flaxseeds triggered a significant increase in the blood concentration of enterolignans, accompanied by fecal excretion of propionate and glycerol. Overall diversity and composition of dominant fecal bacteria remained individual-specific throughout the study. Enterolactone production was linked to the abundance of two molecular species identified as Ruminococcus bromii and Ruminococcus lactaris. Most dominant species of the order Bacteroidales were positively associated with fecal concentrations of either acetic, isovaleric, or isobutyric acid, the latter being negatively correlated with blood levels of triglycerides. The relative sequence abundance of one Gemmiger species (Ruminococcaceae) and of Coprococcus comes (Lachnospiraceae) correlated positively with blood levels of LDL-cholesterol and triglycerides, respectively. CONCLUSION: Flaxseeds increase enterolignan production but do not markedly alter dominant fecal metabolome and bacterial communities. The data underline the possible role of members of the family Ruminococcaceae in the regulation of enterolignan production and blood lipids