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Fathi, A. T. et al. Elevation of urinary 2-hydroxyglutarate in IDH-mutant glioma. Oncologist 21, 214–219 (2016). While the building was under construction in late 1854, Bunsen suggested certain design principles to the university's mechanic, Peter Desaga, and asked him to construct a prototype. Similar principles had been used in an earlier burner design by Michael Faraday, and in a device patented in 1856 by gas engineer R. W. Elsner. The Bunsen/Desaga design generated a hot, sootless, non-luminous flame by mixing the gas with air in a controlled fashion before combustion. Desaga created adjustable slits for air at the bottom of the cylindrical burner, with the flame issuing at the top. When the building opened early in 1855, Desaga had made 50 burners for Bunsen's students. Two years later Bunsen published a description, and many of his colleagues soon adopted the design. Bunsen burners are now used in laboratories around the world. [6] Operation Bunsen burner flames depend on air flow in the throat holes (on the burner side, not the needle valve for gas flow): 1. air hole closed (safety flame used for lighting or default), 2. air hole slightly open, 3. air hole half-open, 4. air hole fully open (roaring blue flame). Chen, J. Y. et al. The oncometabolite R-2-hydroxyglutarate activates NF-κB-dependent tumor-promoting stromal niche for acute myeloid leukemia cells. Sci. Rep. 6, 32428 (2016).

a, b, l-Trp import and degradation dynamics in immune cell subsets exposed to R-2-HG. Intracellular LC–MS/MS measurements of l-Trp and l-Kyn in T cells and monocyte-derived macrophages exposed to 20 mM R-2-HG and varying doses of l-Trp. Top, linear regression of dose-dependent metabolite accumulation. Bottom, quantification of intracellular l-Trp and l-Kyn levels and the [ l-Kyn][ l-Trp] −1 ratio. s.e.m is shown as error bands (top) or bars (bottom). n = 3 independent healthy donors. s.e.m. is projected as error bands. Statistical significance was determined by one-way ANOVA in combination with Tukey’s test. c– e, Cell-free assay of IDO1, IDO2 and TDO2 enzymatic activities with increasing concentrations of synthetic R-2-HG. A nonlinear regression model (log (R-2-HG) versus response) is shown. Regression curves are representative of y = 0 + (0.16 − 0)(1 + 10 (log(EC50)− x)) −1 (EC 50, half-maximum effective concentration). Produced l-Kyn levels were measured by absorbance at 321 nm (A 321). Gray boxes indicate the concentration range of R-2-HG detected in patient glioma tissues 12. n = 2 independent measurements for IDO1, n = 4 independent measurements for IDO2, n = 4 independent measurements for TDO2. f, Expression of Tdo2 in different murine immune cell subsets. RNA-seq data were derived from ref. 27. T n, naive T cell; T eff, effector T cell; T em, effector memory T cell; T gd, γδ T cell; NK, natural killer cell (NK); Mo, monocyte; MG, microglia cell. g, Monocyte-derived macrophage–T cell 3H-dT proliferation assay. Monocyte-derived macrophages from n = 3 Tdo2 +/+ and n = 3 Tdo2 −/− mice were pretreated with 10 mM R-2-HG or vehicle; 10 ng ml −1 anti-IL-10 and anti-TGF-β antibodies (αIL-10/TGF-β) or an isotype (iso) control; 10 ng ml −1 anti-PD-L1 antibody or isotype control; or 10 mM l-Kyn or vehicle as indicated for 24 h and co-cultured with stimulated C57BL6/J T cells for 24 h. Statistical significance was determined by one-way ANOVA in combination with Tukey’s test. If not mentioned otherwise, all data are represented as mean ± s.e.m. Maurer, L. M. et al. pH regulates genes for flagellar motility, catabolism, and oxidative stress in Escherichia coli K-12. J. Bacteriol. 187, 304–319 (2005). First, the use of long peptides, such as the 27-mer H3K27M-vac, is safe irrespective of concomitant anti-PD-1 therapy and suitable to induce mutation-specific CD4 + T cell responses in patients with H3K27M + DMG. The induction of CD4 + T cell-dominated immune responses by long mutation-specific peptide vaccines is similar to that observed in 28 of 30 patients in a first-in-human phase I trial of the long peptide vaccine IDH1-vac in patients with newly diagnosed astrocytomas 20, 21. Notably, CD4 + T cell phenotyping following H3K27M-vac revealed no evidence of induction of immunosuppressive regulatory T cells. While the immunogenicity of the short peptide vaccine H3.3K27M 26-35 is restricted to HLA-A*02 + patients 17, we provide evidence of presentation of H3K27M neoepitope on MHC class II on tumor cells and on APCs across multiple HLA types (Fig. 4). While killing activity of H3K27M-specific CD8 + T cells against HLA-A*02 + tumor cells with endogenous H3.3K27M expression remains controversial 17, 18, 19 we have recently demonstrated that CD4 + T cell interaction with peptide MHC class II in glioma-infiltrating myeloid cells is critical for the fitness of glioma-infiltrating CD8 + T cells 22. Further analyses in a larger clinical trial cohort will assess the suitability of MHC class II expression and neoepitope presentation in DMG as predictive markers for response to H3K27M-vac. Sahm, F. et al. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol. 18, 682–694 (2017). Max Eder Junior Group on Low Grade Gliomas, Heidelberg University Medical Center, Heidelberg, GermanyPartha, Mandal Pratim & Mandal, B. (2002-01-01). A Text Book of Homoeopathic Pharmacy. Kolkata, India: New Central Book Agency. p.46. ISBN 978-81-7381-009-1.

Bopp, L. et al. Multiple stressors of ocean ecosystems in the 21st century: projections with CMIP5 models. Biogeosciences 10, 6225–6245 (2013). The gas can be natural gas (which is mainly methane) or a liquefied petroleum gas, such as propane, butane, or a mixture. Combustion temperature achieved depends in part on the adiabatic flame temperature of the chosen fuel mixture.

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Corporate human rights policies. In March 2021, Facebook adopted a human rights policy meant to adhere to the United Nations Guiding Principles on Business and Human Rights. The policy commits Facebook to the publication of an annual report on human rights interventions undertaken, starting a fund for offline assistance to human rights defenders and journalists, removal of verified misinformation and rumours, partnership with human rights organizations and continuing technological advancement in early warning prioritization of at-risk countries. Whether other companies follow suit remains to be seen. a, Induction of AHR target genes in macrophages by treatment with 20 mM R-2-HG ± 1 µM AHR inhibitor (AHRi) or vehicle as determined by the TaqMan real-time (RT)–PCR AHR signaling array. Fractional differences are shown as indicated. n = 3 pooled healthy human donors. b, Monocyte-derived macrophage T cell-suppression assay. BMDMs of Ahr −/− mice were differentiated in vitro with R-2-HG or vehicle in RPMI 1640 medium containing 5 mg l −1 l-Trp with FBS or l-Trp-free medium with dialyzed FBS for 24 h. Cells were then co-cultured fo Rivers, A. R. et al. Transcriptional response of bathypelagic marine bacterioplankton to the Deepwater Horizon oil spill. ISME J. 7, 2315–2329 (2013).