•Lithological control on geothermal circulation pattern.•Chlorofluorocarbons for mixing analysis.•Fault controlled geothermal system.•Medium enthalpy geothermal system at active volcano.
Besides ...temperature, mineralogy, residence time and dilution are crucial for assessing water-rock interaction intensity. The geothermal system at the Villarrica-Quetrupillán-Lanín volcanic chain, Southern Chile, is located across a prominent lithological transition from plutonic rocks of the North Patagonian Batholith (NPB) to volcano-sedimentary units. With the goal to investigate the impact of lithology on medium-enthalpy geothermal fluids, 15 hot spring discharges were sampled and analyzed for anthropogenic tracers and isotopic composition and compared to the analyses of 31 reservoir rock analogues. Comparison of strontium isotope signatures between rock analogues and hot spring discharges allow an allocation of associated reservoir rocks. Chlorofluorocarbons quantify the dilution of the geothermal springs by shallow groundwater, ranging from almost CFC-free samples to dilution with modern meteoric water by up to 50 %. Fluids discharging from plutonic rocks have low proportions of dilution with modern waters, while hot springs discharging from the volcano-sedimentary rocks have a higher and variable dilution with modern waters. The fractionation of oxygen isotopes of the SO4-H2O system reveals reservoir temperature estimates of 80–100 °C in the plutonic sequence matching discharge temperatures. For the springs discharging from volcano-sedimentary units higher reservoir temperatures of 100–140 °C are calculated. On basis of the analysis, a conceptual reservoir model can be derived. Fast fluid ascent is indicated along Liquiñe-Ofqui fault system in the NPB by similar discharge and reservoir temperatures and low surficial dilution rates. Large differences in discharge and reservoir temperatures in the Cura-Mallín formation along with a high influx of surficial water may be attributed to a more branched pathway pattern. In conclusion lithology maybe an important factor when coming to the utilisation of geothermal resources.
Information on the temperature distribution of subsurface reservoirs is essential for geothermal energy development. One of the promising tools to detect the reservoir temperature distribution is ...temperature-reporting nanoparticle tracers whose functionality has been extensively investigated in both theoretical and experimental ways in the last decade. However, most related studies were limited to simplified geometries and ignored the dynamic interplays of fluid flow, heat transfer, transport and reaction of the temperature-reporting nanoparticle tracer. The response behavior and working mechanisms of such nanotracers in a realistic three-dimensional system still have not been fully revealed through a systematic study. In this work, we develop a numerical modeling approach to simulate field implementation of these nanotracers in a fractured geothermal reservoir. This study aims to evaluate whether the injection of multiple temperature-reporting nanoparticle tracers with different thresholds can be used to estimate the temperature distribution and provide information on the thermal and geological heterogeneities. Several scenarios have been investigated for the geothermal reservoir including homogeneous and non-homogeneous cases (e.g., thermal and geological heterogeneities). Our obtained results from the nanotracer breakthrough curves show that the deviation temperatures in peak concentration values provide an upper limit of the lowest temperature and precise highest temperature for the reservoir temperature range. The deviation temperature of the peak arrival time curve accurately estimates the highest temperature along the main streamlines between the wells. The proposed analysis curves based on the nanotracer breakthrough data were visibly affected by geological heterogeneities including their conductivities and orientations as well as thermal heterogeneities in the geothermal reservoir.
•Temperature-reporting nanoparticle tracer tests are numerically implemented in a 3D fractured geothermal reservoir.•The working mechanisms of the temperature-reporting nanoparticle tracers are illustrated using a proposed modeling approach.•Our proposed analysis curves respond to the reservoir temperature distribution, geological and thermal heterogeneities.
The work presented here offers an approach to estimate the technological
status of lithium extraction from geothermal waters in Germany based on current
scientific studies, as well as to evaluate the ...associated challenges. For this
purpose, the predicted worldwide lithium market, as well as the enormously
increasing German demand due to the planned development of a domestic battery
cell production are presented. From the strongly growing demand, a complete
dependence on poorly diversified global market, a highly strategic importance
of a possible domestic source can be derived. In particular, the study compares
and evaluates different technologies for lithium extraction from thermal waters
such as liquid-liquid extraction, inorganic sorbents, electrochemical methods,
and membrane technologies in terms of their applicability in geothermal
systems. Based on the technology comparison and the current expansion of
geothermal energy in Germany, different scenarios for the extractable amount of
lithium carbonate from geothermal systems in Germany and the French side of the
Upper Rhine Graben were calculated. Thus, taking into account all currently
active wells, a total extraction capacity of about 4,000 tons of lithium
carbonate per year can be predicted.
As estimated by the International Energy Agency, geothermal power can contribute to 3.5 % of worldwide power and 3.9 % to heat production by 2050. This includes the development of enhanced geothermal ...systems (EGSs) in low‐enthalpy systems. EGS technology is still in an early stage of development. Pushing EGS technologies towards market maturity requires a long‐term strategic approach and massive investments in research and development. Comprehensive multidisciplinary research programs that combine fundamental and applied concepts to tackle technological, economic, ecological, and safety challenges along the EGS process chain are needed. The Karlsruhe Institute of Technology (KIT) has defined a broad research program on EGS technology development following the necessity of a transdisciplinary approach. The research concept is embedded in the national research program of the Helmholtz Association and is structured in four clusters: reservoir characterization and engineering, thermal water circuit, materials and geoprocesses, and power plant operation. The proximity to industry, closely interlinked with fundamental research, forms the basis of a target‐orientated concept. The present paper aims to give an overview of geothermal research at KIT and emphasizes the need for concerted research efforts at the international level to accelerate technological breakthrough of EGS as an essential part of a future sustainable energy system.
Harnessing underground power: The Karlsruhe Institute of Technology (KIT), located within the Upper Rhine Graben, takes advantage of favorable geothermal conditions and has defined a comprehensive research program on enhanced geothermal systems technology development following the necessity of a transdisciplinary approach. Research activities cover the whole process chain, including system integration, and span from fundamental to applied research across scales.
The work presented here offers an approach to estimate the technological status of lithium extraction from geothermal waters in Germany based on current scientific studies, as well as to evaluate the ...associated challenges. For this purpose, the predicted worldwide lithium market, as well as the enormously increasing German demand due to the planned development of a domestic battery cell production are presented. From the strongly growing demand, a complete dependence on poorly diversified global market, a highly strategic importance of a possible domestic source can be derived. In particular, the study compares and evaluates different technologies for lithium extraction from thermal waters such as liquid-liquid extraction, inorganic sorbents, electrochemical methods, and membrane technologies in terms of their applicability in geothermal systems. Based on the technology comparison and the current expansion of geothermal energy in Germany, different scenarios for the extractable amount of lithium carbonate from geothermal systems in Germany and the French side of the Upper Rhine Graben were calculated. Thus, taking into account all currently active wells, a total extraction capacity of about 4,000 tons of lithium carbonate per year can be predicted.
Lymphocyte functions triggered by antigen recognition and co-stimulation signals are associated with a rapid and intense cell division, and hence with metabolism adaptation. The nucleotide cytidine ...5' triphosphate (CTP) is a precursor required for the metabolism of DNA, RNA and phospholipids. CTP originates from two sources: a salvage pathway and a de novo synthesis pathway that depends on two enzymes, the CTP synthases (or synthetases) 1 and 2 (CTPS1 with CTPS2); the respective roles of these two enzymes are not known. CTP synthase activity is a potentially important step for DNA synthesis in lymphocytes. Here we report the identification of a loss-of-function homozygous mutation (rs145092287) in CTPS1 in humans that causes a novel and life-threatening immunodeficiency, characterized by an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. In contrast, proximal and distal T-cell receptor (TCR) signalling events and responses were only weakly affected by the absence of CTPS1. Activated CTPS1-deficient cells had decreased levels of CTP. Normal T-cell proliferation was restored in CTPS1-deficient cells by expressing wild-type CTPS1 or by addition of exogenous CTP or its nucleoside precursor, cytidine. CTPS1 expression was found to be low in resting T cells, but rapidly upregulated following TCR activation. These results highlight a key and specific role of CTPS1 in the immune system by its capacity to sustain the proliferation of activated lymphocytes during the immune response. CTPS1 may therefore represent a therapeutic target of immunosuppressive drugs that could specifically dampen lymphocyte activation.
Targeted immunotherapies have greatly changed treatment of patients with B cell malignancies. To further enhance immunotherapies, research increasingly focuses on the tumor microenvironment (TME), ...which differs considerably by organ site. However, immunocompetent mouse models of disease to study immunotherapies targeting human molecules within organ-specific TME are surprisingly rare. We developed a myc-driven, primary murine lymphoma model expressing a human-mouse chimeric CD22 (h/mCD22). Stable engraftment of three distinct h/mCD22+ lymphoma was established after subcutaneous and systemic injection. However, only systemic lymphoma showed immune infiltration that reflected human disease. In this model, myeloid cells supported lymphoma growth and showed a phenotype of myeloid-derived suppressor cells. The human CD22-targeted immunotoxin Moxetumomab was highly active against h/mCD22+ lymphoma and similarly reduced infiltration of bone marrow and spleen of all three models up to 90-fold while efficacy against lymphoma in lymph nodes varied substantially, highlighting relevance of organ-specific TME. As in human aggressive lymphoma, anti-PD-L1 as monotherapy was not efficient. However, anti-PD-L1 enhanced efficacy of Moxetumomab suggesting potential for future clinical application. The novel model system of h/mCD22+ lymphoma provides a unique platform to test targeted immunotherapies and may be amenable for other human B cell targets such as CD19 and CD20.
Background Primary immunodeficiencies are a rare group of inborn diseases characterized by a broad clinical and genetic heterogeneity. Substantial advances in the identification of the underlying ...molecular mechanisms can be achieved through the study of patients with increased susceptibility to specific infections and immune dysregulation. We evaluated 3 siblings from a consanguineous family presenting with EBV-associated B-cell lymphoproliferation at an early age (12, 7½, and 14 months, respectively) and profound naive T-cell lymphopenia. Objective On the basis of the hypothesis of a rare inborn immunodeficiency of autosomal recessive inheritance, we sought to characterize the underlying genetic defect. Methods We performed genome-wide homozygosity mapping, followed by whole-exome sequencing. Results We identified a homozygous inherited missense mutation in the gene encoding Coronin-1A (CORO1A) in the 3 siblings. This mutation, p. V134M, results in the substitution of an evolutionarily conserved amino acid within the β-propeller domain, which abrogates almost completely the protein expression in the patients' cells. In addition to a significant diminution of naive T-cell numbers, we found impaired development of a diverse T-cell repertoire, near-to-absent invariant natural killer T cells, and severely diminished mucosal-associated invariant T cell numbers. Conclusions Our findings define a new clinical entity of a primary immunodeficiency with increased susceptibility to EBV-induced lymphoproliferation in patients associated with hypomorphic Coronin-1A mutation.
Introduction Muscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor ( ...EGFR ) is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the EGFR ligands AREG and EREG have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma. Materials and methods We investigated the prognostic significance of EGFR , AREG , and EREG in MIBC. Gene expression and copy number analyses were performed via qRT-PCR on tissue samples from 100 patients with MIBC who underwent radical cystectomy at the University Hospital Mannheim (MA; median age 72, interquartile range IQR 64–78 years, 25% female). Results were validated in 361 patients from the 2017 TCGA MIBC cohort (median age 69, IQR 60–77 years, 27% female), in the Chungbuk and MDACC cohort. Gene expressions were correlated with clinicopathologic parameters using the Mann-Whitney test, Kruskal-Wallis- test and Spearman correlation. For overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) gene expression was analyzed with Kaplan-Meier and Cox-proportional hazard models. Results Significant gene expression differences in EGFR , AREG , and EREG could be detected in all cohorts. In the TCGA cohort, EGFR expression was significantly elevated in patients with EGFR amplification and KRAS wildtype. High AREG expression independently predicted longer OS (HR = 0.35, CI 0.19 - 0.63, p = 0.0004) and CSS (HR = 0.42, CI 0.18 – 0.95, p = 0.0378) in the MA cohort. In the TCGA cohort, high EGFR , AREG , and EREG expression correlated with shorter OS ( AREG : HR = 1.57, CI 1.12 – 2.20, p = 0.0090) and DFS ( EGFR : HR = 1.91, CI 1.31 – 2.8, p = 0.0008). EGFR amplification was also associated with reduced DFS. Discussion High EGFR and EREG indicate worse survival in patients with MIBC. The prognostic role of AREG should further be investigated in large, prospective series. Divergent survival outcomes between the four cohorts should be interpreted cautiously, considering differences in analysis methods and demographics. Further in vitro investigations are necessary to elucidate the functional mechanisms underlying the associations observed in this study.
The first example for the photocatalytic generation of a highly electrophilic intermediate that is not based on radical reactivity is reported. The single‐electron reduction of bench‐stable and ...commercially available 4‐(trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its fragmentation into fluorophosgene and benzonitrile. The in situ generated fluorophosgene was used for the preparation of carbonates, carbamates, and urea derivatives in moderate to excellent yields via an intramolecular cyclization reaction. Transient spectroscopic investigations suggest the formation of a catalyst charge‐transfer complex‐dimer as the catalytic active species. Fluorophosgene as a highly reactive intermediate, was indirectly detected via its next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR analyses provided a comprehensive reaction mechanism including a water dependent off‐cycle equilibrium.
Fluorophosgene was liberated by the photocatalytic reduction of a simple aryltrifluoromethoxyether. This highly reactive species was used for the synthesis of cyclic carbonates, carbamates and urea derivatives. The reaction mechanism was investigated by an in‐depth NMR study as well as cyclovoltammetry and transient spectroscopy which suggests a charge‐transfer complex dimer as the catalytic active species.
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