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Abstract. Although an excellent nitrogen source for most bacteria, ammonium was-in analogy to plant and animal systems-assumed be detrimental to bacteria when present in high concentrations. In this study, we examined the effect of molar ammonium concentrations on different model bacteria, namely, Corynebacterium glutamicum, Escherichia coli, and Bacillus subtilis. The studied bacteria are highly resistant to ammonium. When growth was impaired upon addition of molar (NH 4 ) 2 SO 4 concentrations, this was not caused by an ammonium-specific effect but was due to an enhanced osmolarity or increased ionic strength of the medium. Therefore, it was concluded that ammonium is not detrimental to C. glutamicum and other bacteria even when present in molar concentrations.Ammonium (in this communication, the term ''ammonium'' is used in a general sense, including NH 4 + and NH 3 ; distinct ammonium species are indicated by chemical formula) is the preferred nitrogen source for most bacteria and fungi, and also plants acquire ammonium as a nitrogen source from the soil [35]. When present in high concentrations, diffusion of NH 3 , which is in equilibrium with NH 4 + , across the cytoplasmic membrane into the cell is sufficient to promote growth. In a situation of ammonium limitation, diffusion becomes negligible and special carriers are synthesized in bacteria, fungi, and plants (for a recent review, see [36]).However, ammonium is a paradoxical nutrient, because it is notorious for its cytotoxic effects. Furthermore, active transport of ammonium can to lead to a harmful energy-wasting futile cycling when accumulated ammonium diffuses across the cytoplasmic membrane back into the medium. Sensitivity to ammonium is discussed to be a universal phenomenon; however, it is well investigated only in plant and animal systems [36], whereas the situation in bacteria is less clear.

BackgroundThe PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking.Patients and methodsWe assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients.ResultsA significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient's outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases.ConclusionsIn summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.STATEMENT OF TRANSLATIONAL RELEVANCEIn spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1.Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.

A new and powerful active anode system that can be operated in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) has been discovered. In HFIP the molybdenum anode forms a compact, conductive, and electroactive layer of higher-valent molybdenum species. This system can replace powerful but stoichiometrically required Mo reagents for the dehydrogenative coupling of aryls. This electrolytic reaction is more sustainable and allows the conversion of a broad scope of activated arenes.

We have investigated the impact of rapid thermal annealing (RTA) induced vacancy supersaturation on oxide precipitation based as much as possible on experimental and theoretical values. Oxygen precipitation after RTA processing was found to be controlled by the initial concentration of interstitial oxygen in a sixth power dependency and frozen vacancies just in a cubic dependency. The formation of tensile strained nVO2 clusters seems to be the favored process for coherent nucleation of oxide precipitates. The reduction of interstitial oxygen can be accurately modeled for the temperature range from 1150 to 1250°C using Ham’s theory for precipitate growth and an empirical relation based on nucleation of oxide precipitates by agglomeration of VO2 complexes. During RTA treatments at temperatures ≥1300°C vacancies seem to be consumed by other processes. Below RTA temperatures of 1150°C , oxide precipitation is dominated by shrunken as-grown precipitate nuclei because as-grown nuclei can be dissolved only at RTA temperatures ≥1150°C .