Autocrine Adenosine Regulates Tumor Polyfunctional CD73⁺CD4⁺ Effector T Cells Devoid of Immune Checkpoints.

The production of CD73-derived adenosine (Ado) by Tregs has been proposed as a resistance mechanism to anti-PD-1 therapy in murine tumor models. We reported that human Tregs express the ectonucleotidase CD39, which generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4 <sup>+</sup> T cells (Teffs) enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6, and MDR1, and production of IL17A/IFNγ/IL22/GM-CSF. CD39 <sup>+</sup> Tregs selectively targeted CD73 <sup>+</sup> Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73 <sup>+</sup> Teffs to secrete IL17A. CD73 <sup>+</sup> Teffs infiltrating breast and ovarian tumors were functionally blunted by Tregs expressing upregulated levels of CD39 and ATPase activity. Moreover, tumor-infiltrating CD73 <sup>+</sup> Teffs failed to express inhibitory immune checkpoints, suggesting that CD73 might be selected under pressure from immune checkpoint blockade therapy and thus may represent a nonredundant target for restoring antitumor immunity.Significance: Polyfunctional CD73 <sup>+</sup> T-cell effectors lacking other immune checkpoints are selectively targeted by CD39 overexpressing Tregs that dominate the breast tumor environment. Cancer Res; 78(13); 3604-18. ©2018 AACR

Drilling engineering experience gained from MD-BTES construction phase of SKEWS demo-site

As a result of the current energy crisis triggered by war and increasing shortage of resources, renewable energy sources are becoming increasingly important. The storage of heat from fluctuating energy sources is an essential component for independent and base-load capable energy supply. A promising technology are medium-deep geothermal storage systems, which store excess heat in the crystalline subsurface and offer significant advantages over near-surface geothermal storage systems. At the Lichtwiese campus of the Technical University of Darmstadt, the world's first medium-deep research geothermal storage system was constructed in the crystalline bedrock with three 750 m deep boreholes with a distance of approx. 8.6 m (research project SKEWS, project administrator Jülich, funding code 03EE4030A). The outer casing of the coaxial system has a diameter of 7", on which an attached glass fiber cable records temperature and strain measurements. Research operations began in the spring of 2023, which consists of an initial enhanced Geothermal Response Test (eGRT) followed by five heating and cooling phases. The experience and knowledge acquired are intended to demonstrate the basic construction and operational feasibility of such storage systems, as well as to be used as a basis for the planning, dimensioning, construction and costing of future projects. With the current project status, it has already been possible to evaluate the processes of the drilling phase and their effects on the drilling operation. The encountering of deviating geological and hydrogeological conditions to the prognosis from the planning phase required, among other things, the change of the drilling technique from water hammer to rotary drilling with a clay-fresh-water fluid and accordingly also affected the verticality of the drillings. Based on the detailed drilling data recorded and the geological conditions explored, the drilling phase of the storage system could be evaluated in terms of its material usage, drilling accuracy, costs and energy consumption

Nuisibilité au champ des deux principaux virus des pois protéagineux. Des essais sur le virus de la mosaïque énation du pois (PEMV) et sur le Pea seed-borne mosaic virus (PSbMV)

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Graduate Geothermal training in the European Economic Area

Intensive graduate courses in geothermal energy have traditionally been the remit of nations with a long tradition of high temperature geothermal utilization: Iceland, Italy, Japan, and New Zealand. In addition, El Salvador has had a Spanish language Geothermal Diploma Course for Latin America since 2010, courses in Indonesia, taught in Indonesian, and African geothermal training is under development. However, increasing impacts of climate change, geopolitical conflict and related refugee movement has drawn attention to the need for clean, renewable and sustainable energy worldwide. This attention has created interest in geothermal research and utilization in many countries that do not have high temperature, tectonic margin or volcano-related, geothermal systems. This paper discusses the ongoing development of an EU-funded European Erasmus + Strategic Partnership dealing aiming at the construction of a geothermal course curriculum for international students, involving Iceland France, Germany and Croatia

Longitudinal Stern-Gerlach effect for slow cesium atoms

The mechanical Stern-Gerlach effect is investigated in the case of a slow atomic cloud falling through an inhomogeneous magnetic field featuring a strong longitudinal gradient. The resulting Zeeman sublevel state selection is demonstrated under various experimental conditions. Longitudinal spatial separations are in agreement with numerical simulations that take into account the gravitational acceleration and both the transverse and axial magnetic forces. Since separations greater than 20 cm are obtained, potential applications in atom optics are outlined