Despite considerable interest in the modulation of tumor-associated Foxp3 + regulatory T cells (T regs ) for therapeutic benefit, little is known about the developmental origins of these cells and ...the nature of the antigens that they recognize. We identified an endogenous population of antigen-specific T regs (termed MJ23 T regs ) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 T regs were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 T regs underwent autoimmune regulator (Aire)—dependent thymic development in both male and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific T regs , which are likely coopted by tumors developing within the associated organ.
Legal frameworks lay down requirements for risk assessment of combined exposure to multiple chemicals and their implementation where scientific methods are accepted by responsible authorities. In ...order to protect human health, an assessment of potential risks that might result from co-exposure to multiple chemical substances is requested by European legislation. Several approaches for risk assessment of mixtures of chemicals have been proposed, but none has been widely implemented in regulatory risk assessments, so far. EuroMix, an EU Horizon 2020 funded project, contributed to the improvement of internationally harmonised approaches for risk assessment of chemical mixtures. Based on in vitro and in silico tests, an integrated test strategy involving hazard and exposure assessment was developed and a web tool to conduct such assessments was provided. One further task within EuroMix was to make recommendations for international harmonisation, implementation and further development of suitable scientific approaches regarding the assessment of mixture effects. This paper briefly describes objectives and outcome of the EuroMix project as well as recent findings from OECD, WHO and EFSA addressing combined exposure to multiple chemicals. Building on this, five steps addressing further development needs and implementation of existing tools especially for risk managers and policy makers are proposed.
•International organisations intensify efforts to develop guidance to assess combined exposure to multiple chemicals.•EuroMix methodology supports addressing mixtures across regulatory sectors.•Harmonised implementations of risk assessment strategies for chemical mixtures are recommended.•Research and development needs in regulatory risk assessment and management are defined.•A procedure to further encourage harmonised risk assessment of chemical mixtures is proposed.
We evaluated the radiopacity and antibacterial properties of various concentrations of double antibiotic paste (DAP) containing barium sulfate (BaSO4) or zirconium oxide (ZrO2) radiopaque agents.
The ...radiopacity of 1, 10, and 25 mg/mL DAP containing 30% (w/v) BaSO4 or ZrO2, DAP-free radiopaque pastes, and commercially available radiopaque calcium hydroxide (CaOH2) were evaluated according to ISO 6876/2001 with slight modifications (n = 6 per group). Dentin samples (n = 70) infected anaerobically for 3 weeks with bacterial biofilms obtained from a root canal of an immature tooth with pulpal necrosis were treated with similar experimental pastes or received no treatment (n = 7). After 1 week, the pastes were rinsed off, and biofilm disruption assays were conducted. To show the residual antibacterial effects, sterile dentin samples (n = 70) were pretreated for 1 week with the same pastes (n = 7). The pastes were rinsed off, and the samples were immersed in phosphate-buffered saline for 24 hours and infected anaerobically with the same bacterial biofilm mentioned earlier for 3 weeks before conducting biofilm disruption assays. Sterile dentin blocks were used in both antibacterial analyses as negative control groups (n = 7). Wilcoxon rank sum tests were used for statistical analyses.
No tested concentrations of BaSO4 DAP or ZrO2 DAP showed significant differences from Ca(OH)2 in radiopacity. However, all tested concentrations of BaSO4 DAP, ZrO2 DAP, and Ca(OH)2 exhibited significant direct antibacterial effects. ZrO2 DAP at 1 mg/mL and Ca(OH)2 did not show significant residual antibacterial effects.
BaSO4 DAP at 1 mg/mL provided significantly superior residual antibacterial effects and comparable radiopacity with the commercially available Ca(OH)2.
Precipitation and catchment characteristics of mountainous headwaters can vary largely within short distances. It remains unclear how these two factors determine the contribution of event water and ...pre-event water to stormflow. We investigated this in five neighboring headwaters with high annual precipitation amounts (>2,000 mm y−1) in a steep pre-alpine region in Switzerland. Rainfall and streamwater of 13 different rainstorms were sampled (P: 5 mm intervals, Q: 12 to 51 samples per events) to perform a two-component isotope hydrograph separation. Pre-event water contributions based on δ18O or δ2H computation were similar. The pre-event water contributions of headwaters depended largely on rainfall (amount and intensity) and varied more between events than between catchments, despite clear differences in land cover between the catchments. Furthermore, antecedent wetness was not found to control pre-event water contribution. With increasing rainfall amount, the proportion of rainfall in runoff increased and changed from pre-event to event water dominated. The variable rainfall amount and small active storage (organic soil horizon, 20–50 cm) resulted in a threshold in the upper soil horizon with subsequently more variable pre-event water contribution. Our results show the necessity of sampling in different headwaters and events to better understand controlling factors in runoff generation.
•Spatial variability in rainfall and its isotopic composition was high and differed for each event.•No relation between rainfall isotopic composition and rainfall characteristics or ...elevation.•Spatial variability in rainfall isotopic composition affected isotope hydrograph separation.
Isotope hydrograph separation (IHS) is a valuable tool to study runoff generation processes. To perform an IHS, samples of baseflow (pre-event water) and streamflow are taken at the catchment outlet. For rainfall (event water) either a bulk sample is collected or it is sampled sequentially during the event. For small headwater catchment studies, event water samples are usually taken at only one sampling location in or near the catchment because the spatial variability in the isotopic composition of rainfall is assumed to be small. However, few studies have tested this assumption. In this study, we investigated the spatiotemporal variability in the isotopic composition of rainfall and its effects on IHS results using detailed measurements from a small pre-alpine headwater catchment in Switzerland. Rainfall was sampled sequentially at eight locations across the 4.3km2 Zwäckentobel catchment and stream water was collected in three subcatchments (0.15, 0.23, and 0.70km2) during ten events. The spatial variability in rainfall amount, average and maximum rainfall intensity and the isotopic composition of rainfall was different for each event. There was no significant relation between the isotopic composition of rainfall and total rainfall amount, rainfall intensity or elevation. For eight of the ten studied events the temporal variability in the isotopic composition of rainfall was larger than the spatial variability in the rainfall isotopic composition. The isotope hydrograph separation results, using only one rain sampler, varied considerably depending on which rain sampler was used to represent the isotopic composition of event water. The calculated minimum pre-event water contributions differed up to 60%. The differences were particularly large for events with a large spatial variability in the isotopic composition of rainfall and a small difference between the event and pre-event water isotopic composition. Our results demonstrate that even in small catchments the spatial variability in the rainfall isotopic composition can be significant and has to be considered for IHS studies. Using data from only one rain sampler can result in significant errors in the estimated pre-event water contributions to streamflow.
Amending soils with biochar, a pyrolyzed organic material, is an emerging practice to potentially increase plant available water and reduce the risks associated with climatic variability in ...traditionally‐rainfed tropical agricultural systems. To investigate the impacts of biochar amendment on soil water storage relative to non‐amended soils, we performed an upland rice field experiment in a tropical seasonally dry region of Costa Rica consisting of plots with two different biochar amendments and a control plot. Across all plots, we collected hydrometric and isotopic data (δ18O and δ2H of rain, mobile soil, ground and rice xylem water). We observed that the soil water retention curves for biochar treated soils shifted, indicating that rice plants had 2% to 7% more water available throughout the growing season relative to the control plots and thus could withstand dry spells up to seven extra days. Furthermore, the isotopic composition of plant water in biochar and control treatments were rather similar, indicating that rice plants in different treatments likely consumed similar water. Hence, we observed that biochar amendments can stabilize water supplies for the rice plants; however, still supplemental irrigation was required to facilitate plant growth during extended dry periods. Ultimately, our findings indicate, that biochar amendments can complement, but not necessarily replace, other water management strategies to help reduce the threat of rainfall variability to rainfed agriculture in tropical regions.
How does biochar impact soil water storage? After adding biochar to an upland rice field in Costa Rica, we observed a shift in the soil water retention curves, indicating that rice plants had 2%–7% more water available. The isotopic composition of plant water did not vary with biochar, indicating rice plants likely consumed similar water. Hence, biochar amendment can stabilize water supply for rice plants, but not necessarily replace, other water management strategies.
When Yuri Andropov offered to divulge how the Komitet Gosudarstvennoy Bezopasnosti (KGB) foiled an important Central Intelligence Agency (CIA) operation, Julian Semyonov ("Lubyanka's nightingale") ...jumped at the chance to write a spy thriller based on real people and events. TASS is Authorized to Announce ... (1979) is a fictional version of a CIA operation involving Soviet diplomat Aleksandr Ogorodnik (a.k.a. TRIGON). The novel confirms Director of Central Intelligence Stansfield Turner's suspicion that Ogorodnik was a KGB dangle whose rumored suicide was false. It also foreshadowed the KGB's bogus claim that the CIA was an accessory to Ogorodnik's murder of his mistress. Andropov sponsored the work of fiction as a subtle way of revealing clues that he had outfoxed the Agency.
People unfamiliar with Chinese characters show poorer visual working memory (VWM) performance for Chinese characters than do literates in Chinese. In a series of experiments, we investigated the ...reasons for this expertise advantage. Experiments 1 and 2 showed that the advantage of Chinese literates does not transfer to novel material. Experts had similar resolution as novices for material outside of their field of expertise, and the memory of novices and experts did not differ when detecting a big change, e.g., when a character's color was changed. Memorizing appears to function as a rather abstract representation of word forms because memory for characters' fonts was poor independently of expertise (Experiment 3), though still visual. Distractors that were highly similar conceptually did not increase memory errors, but visually similar distractors impaired memory (Experiment 4). We hypothesized that literates in Chinese represent characters in VWM as tokens of visual word forms made available by long-term memory. In Experiment 5, we provided novices with visual word form knowledge. Participants subsequently performed a change detection task with trained and novel characters in a functional magnetic resonance experiment. We analyzed set size- and training-dependent effects in the intraparietal sulcus (IPS) and the visual word form area. VWM for trained characters was better than for novel characters. Neural activity increased with set size and at a slower rate for trained than for novel characters. All conditions approached the same maximum, but novel characters reached the maximum at a smaller set size than trained characters. The time course of the bold response depended on set size and knowledge status. Starting from the same initial maximum, neural activity at small set sizes returned to baseline more quickly for trained characters than for novel characters. Additionally, high performers showed generally more neural activity in the IPS than low performers. We conclude that experts' better performance in working memory (WM) is caused by the availability of visual long-term representations (word form types) that allow a sparse representation of the perceived stimuli and make even small changes big because they cause a type change that is easily detected.
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