Polychromatic Laser Guide Star. Progress report and modeless laser

International audienceWe report the current status of the polychromatic laser guide star pro-gramme ELP-OA, and the new developments: the modeless laser allowinga continuous match of the laser FWHM with that of the Na D2 line in themesosphere, and ATTILA the ¯rst bench of the ELP-OA demonstrator

Re-establishing glacier monitoring in Kyrgyzstan and Uzbekistan, Central Asia

Glacier mass loss is among the clearest indicators of atmospheric warming. The observation of these changes is one of the major objectives of the international climate monitoring strategy developed by the Global Climate Observing System (GCOS). Long-term glacier mass balance measurements are furthermore the basis for calibrating and validating models simulating future runoff of glacierised catchments. This is essential for Central Asia, which is one of the driest continental regions of the Northern Hemisphere. In the highly populated regions, water shortage due to decreased glacierisation potentially leads to pronounced political instability, drastic ecological changes and endangered food security. As a consequence of the collapse of the former Soviet Union, however, many valuable glacier monitoring sites in the Tien Shan and Pamir Mountains were abandoned. In recent years, multinational actors have re-established a set of important in situ measuring sites to continue the invaluable long-term data series. This paper introduces the applied monitoring strategy for selected glaciers in the Kyrgyz and Uzbek Tien Shan and Pamir, highlights the existing and the new measurements on these glaciers, and presents an example for how the old and new data can be combined to establish multi-decadal mass balance time series. This is crucial for understanding the impact of climate change on glaciers in this region

Numerical analysis and simulation of the dynamics of mountain glaciers

In this chapter, we analyze and approximate a nonlinear stationary Stokes problem that describes the motion of glacier ice. The existence and uniqueness of solutions are proved and an a priori error estimate for the finite element approximation is found. In a second time, we combine the Stokes problem with a transport equation for the volume fraction of ice, which describes the time evolution of a glacier. The accumulation due to snow precipitation and melting are accounted for in the source term of the transport equation. A decoupling algorithm allows the diffusion and the advection problems to be solved using a two-grids method. As an illustration, we simulate the evolution of Aletsch glacier, Switzerland, over the 21st century by using realistic climatic conditions

Global glacier change in the 21st century: Every increase in temperature matters

Glacier mass loss affects sea level rise, water resources, and natural hazards. We present global glacier projections, excluding the ice sheets, for shared socioeconomic pathways calibrated with data for each glacier. Glaciers are projected to lose 26 ± 6% (+1.5°C) to 41 ± 11% (+4°C) of their mass by 2100, relative to 2015, for global temperature change scenarios. This corresponds to 90 ± 26 to 154 ± 44 millimeters sea level equivalent and will cause 49 ± 9 to 83 ± 7% of glaciers to disappear. Mass loss is linearly related to temperature increase and thus reductions in temperature increase reduce mass loss. Based on climate pledges from the Conference of the Parties (COP26), global mean temperature is projected to increase by +2.7°C, which would lead to a sea level contribution of 115 ± 40 millimeters and cause widespread deglaciation in most mid-latitude regions by 2100

Interleukin-2 treatment effect on imatinib pharmacokinetic, P-gp and BCRP expression in mice:

The aim of this study was to investigate the effect that recombinant interleukin-2 (rIL-2) (0.16 MUI/injection) had on the pharmacokinetics of imatinib (IM) in plasma. In this study, IM was given orally to mice at a dose of 150 mg/kg once a day for 11 days (from day 1 to 11) either alone or in combination with intraperitoneal injections of rIL-2 twice a day from day 8 to 11. Pharmacokinetic parameters were determined using WinNonLin software. Areas under the curve were compared using Bailer\u27s method. The repeated administration of the rIL-2+IM combination was shown to have two pharmacokinetic advantages compared with repeated IM doses alone. In addition to the pharmacodynamic interest of this treatment, we found that the combined treatment significantly increased the IM Cmax (P<0.05) and significantly increased the IM trough concentration (C24 h) (P<0.01), which was always above the minimum therapeutic IM concentration (1 μmol/l) in plasma. Those pharmacokinetic modifications may be explained, in part, by a decrease in the P-glycoprotein expression in the three intestinal segments of the mice (duodenum, P<0.01; jejunum, P<0.05; and ileum, P<0.05) and a decrease in BCRP expression in the duodenum segment (P<0.05) due to rIL-2. In another experiment, we found a significant induction of intestinal P-glycoprotein expression in mice that had been given IM orally (150 mg/kg) twice a day for 11 days. It would be interesting to further investigate the IM disposition associated with rIL-2 treatment for clinical applications

Cetuximab increases concentrations of irinotecan and of its active metabolite SN-38 in plasma and tumour of human colorectal carcinoma-bearing mice

In a previous study, we showed that cetuximab, a monoclonal antibody directed towards epidermal growth factor receptor, could inhibit P-glycoprotein (P-gp), an efflux protein of ATP-binding cassette family, and lead to an increased P-gp substrate intracellular concentration. Cetuximab is given with irinotecan to patients with metastasis colorectal cancer who did not respond to irinotecan-based therapy. The mechanism of this successful clinical reversion remains unknown. As irinotecan is a P-gp substrate, we tested here whether cetuximab could modify irinotecan concentration in mice. Therefore, concentrations of irinotecan and of its active metabolite SN-38 were measured by HPLC in plasma and tumour of mice bearing a human colorectal carcinoma xenograft when irinotecan is given orally alone or after a pretreatment with cetuximab. Pharmacokinetic analysis showed no significant modification of irinotecan concentrations but a significant increase (1.7-fold) in SN-38 AUCs in plasma and in tumour after a pretreatment with cetuximab. Those results suggest that cetuximab influence irinotecan distribution into tissues probably due to inhibition of P-gp. As SN-38 is 200-fold more potent than irinotecan, cetuximab could reverse irinotecan resistance by an effect on its active metabolite. Inhibiting SN-38 efflux by P-gp drug transporters in biliary system and tumour can lead to pharmacokinetic modification and a higher anticancer efficacy

Accuracy of a questionnaire for identifying respiratory allergies in epidemiological studies

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Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya

On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27x106 m3 of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders &gt;20 m in diameter, and scoured the valley walls up to 220 m above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments

Twenty-first century glacier slowdown driven by mass loss in High Mountain Asia

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