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A recurring challenge in quantum science and technology is the precise control of their underlying dynamics that lead to the desired quantum operations, often described by a set of quantum gates. These gates can be subject to application-specific errors, leading to a dependence of their controls on the chosen circuit, the quality measure and the gate-set itself. A natural solution would be to apply quantum optimal control in an application-oriented fashion. In turn, this requires the definition of a meaningful measure of the contextual gate-set performance. Therefore, we explore and compare the applicability of quantum process tomography, linear inversion gate-set tomography, randomized linear gate-set tomography, and randomized benchmarking as measures for closed-loop quantum optimal control experiments, using a macroscopic ensemble of nitrogen-vacancy centers in diamond as a test-bed. Our work demonstrates the relative trade-offs between those measures and how to significantly enhance the gate-set performance, leading to an improvement across all investigated methods., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Myeloid-derived suppressor cells (MDSCs) inhibit T-cell expansion and functions by versatile mechanisms such as nutrient depletion, nitrosylation, or apoptosis. Since graft-versus-host disease (GVHD) is characterized by the expansion of donor-derived T cells destroying recipient tissue, we analyzed whether MDSCs can be used for GVHD prevention in murine allogeneic bone marrow transplantation models. Transplantation of MDSCs, generated from bone marrow cells by granulocyte-macrophage colony-stimulating factor (GM-CSF)/G-CSF in vitro, inhibited GVHD-induced death and attenuated histologic GVHD, whereas antitumor cytotoxicity of alloantigen-specific T cells was maintained. MDSCs expanded in vivo and invaded lymphatic and GVHD target organs. Major histocompatibility complex class I expression on MDSCs was dispensable for their suppressive capacity. Inhibition of GVHD required the presence of MDSCs during T-cell priming, whereas allogeneic T-cell numbers and homing in lymphoid and GVHD target organs were not considerably affected in MDSC-treated mice. However, MDSCs skewed allogeneic T cells toward type 2 T cells upregulating T helper 2 (Th2)-specific cytokines. Type 2 T-cell induction was indispensable for GVHD prevention since MDSC treatment failed to prevent GVHD when allogeneic STAT6-deficient T cells, which are unable to differentiate into Th2 cells, were transplanted. MDSC-induced Th2 induction might be applicable for GVHD treatment in clinical settings., (© 2015 by The American Society of Hematology.)

The eukaryotic tRNA:guanine transglycosylase (TGT) catalyses the base-for-base exchange of guanine for queuine (the q-base)--a nutrition factor for eukaryotes--at position 34 of the anticodon of tRNAsGUN (where 'N' represents one of the four canonical tRNA nucleosides), yielding the modified tRNA nucleoside queuosine (Q). This unique tRNA modification process was investigated in HeLa cells grown under either aerobic (21% O2) or hypoxic conditions (7% O2) after addition of chemically synthesized q-base to q-deficient cells. While the q-base was always inserted into tRNA under aerobic conditions, HeLa cells lost this ability under hypoxic conditions, however, only when serum factors became depleted from the culture medium. The inability to insert q into tRNA did not result from a lack of substrate, because the q-base accumulated within these cells against the concentration gradient, suggesting the presence of an active transport system for this base in HeLa cells. The activity of the TGT enzyme was restored after treatment of the cells with the protein kinase C activator, TPA, even in the presence of mRNA or protein synthesis inhibitors. The results indicate that the eukaryotic tRNA modifying enzyme, TGT, is a downstream target of activated protein kinase C.

Queuine (q), a cyclopentendiol derivative of 7-aminomethyl-7-deazaguanine, is a nutrient factor for lower and higher eukaryotes, except yeast; it is synthesized in eubacteria partly at the level of tRNA. In eukaryotes q is preferentially inserted into the wobble position of specific tRNAs in differentiated and adult tissues, but occurs mainly free in embryonic and fast proliferating cells. HeLa cells grow to a higher cell density under aerobic than under hypoxic conditions only when supplemented with q. Here we show that in hypoxically grown HeLa cells, sufficiently supplied with q, free q accumulated when serum factors become limiting while the respective tRNAs remained completely q deficient. In these cells the levels of lactate dehydrogenase A (LDH A) mRNA and of LDH A protein were at least twofold higher than in aerobically grown cells, independent of the absence or presence of q. In response to q the LDH A4 isoenzyme was further activated by a post-translational mechanism. In q-deficient HeLa cells the activity of the major anoxic stress protein, LDHk, increased as a result of hypoxia; this increase was suppressed by q. In aerobically grown, q-deficient cells significant activities of LDH A4 and LDHk were present; both activities were markedly lowered by q, while the mitochondrial electron flow was improved. The results show that free q is essential for relieving hypoxic stress in HeLa cells that results from oxygen limitation.

Addition of the q-base to q-deficient non-transformed mammalian cells stimulated their proliferation. The q-base also improved proliferation of some cancer-derived cell lines, but inhibited proliferation of others. The proliferation of HeLa-S3 carcinoma cells was stimulated by q under aerobic conditions, but was inhibited when the cells had shifted their energy metabolism towards glycolysis as the result of oxygen limitation. Q-deficient cells could not adapt their proliferation to the respective oxygen tension. The q-base stimulated the proliferation of non-transformed fibroblasts but inhibited proliferation of the same cell line, when aerobic glycolysis was increased after transformation with the ras gene. The results suggest that the q-base permits mammalian cells to adapt their proliferation to their specific metabolic state.

Epidermal growth factor (EGF) induces autophosphorylation of its cognate receptor at tyrosine residues. Here we show that queuine (q), a widely distributed modified guanine analogue occurring free or as a tRNA wobble base, modulates this EGF receptor activity in vitro and in intact cells. Autophosphorylation of the immunopurified receptor from human A431 epidermoid carcinoma cells was enhanced three to fourfold in the presence of physiological concentrations of q. Using a membrane fraction of A431 cells, a twofold increase in autophosphorylation activity in the presence of q was observed, however, only when the receptor was activated by the ligand. In intact A431 cells, q enhanced the initial ligand-induced autophosphorylation of the EGF receptor three to fourfold. However, upon longer treatment of the cells with EGF in the presence of q, significantly less autophosphorylated receptor was detectable compared with stimulation of cells in the absence of q. A similar q-dependent modulation of EGF receptor autophosphorylation was observed also in human cervical carcinoma cells HeLa-S3. Treatment of q-deficient HeLa cells with EGF induced the c-fos gene expression, transiently increased the activity of the anoxic stress protein LDH k, and stimulated proliferation. Treatment of HeLa cells with EGF in the presence of q resulted in a delayed c-fos gene expression and an accelerated increase and decrease of LDH k activity. The stimulatory effect of low doses of EGF on HeLa cell proliferation was completely antagonized in the presence of q. The results suggest that the mitogenic signalling initiated by the EGF receptor is modulated by q.

HeLa cells can be grown in media supplemented with horse serum that is lacking the nutrient factor queuine. The addition of 1 X 10(-8) M queuine to aerobically grown cells caused a slight, but significant, inhibition of growth, whereas cell proliferation was stimulated increasingly when the concentration of queuine was raised from 3 X 10(-8) M to 3 X 10(-7) M. This was also observed when the cells were transiently starved of serum factors. When the cells were grown under hypoxic stress, but otherwise identical conditions, they responded to queuine in an opposite manner. Under conditions of mitogenic stimulation, characteristic new proteins were found in cytosolic, nuclear and mitochondrial fractions of aerobically grown cells. The effects of queuine on cell proliferation at low concentrations are assumed to be mediated by the free base, whereas the effects at higher concentrations possibly involve both, queuine and Q-tRNAs. The 'Q system' appears to mediate growth control in dependence on oxygen availability.