Single dye molecules at cryogenic temperatures display many spectroscopic phenomena known from free atoms and are thus promising candidates for fundamental quantum optical studies. However, the existing techniques for the detection of single molecules have either sacrificed the information on the coherence of the excited state or have been inefficient. Here we show that these problems can be addressed by focusing the excitation light near to the absorption cross section of a molecule. Our detection scheme allows us to explore resonance fluorescence over 9 orders of magnitude of excitation intensity and to separate its coherent and incoherent parts. In the strong excitation regime, we demonstrate the first observation of the Mollow triplet from a single solid-state emitter. Under weak excitation we report the detection of a single molecule with an incident power as faint as 150 attoWatt, paving the way for studying nonlinear effects with only a few photons. * Electronic address: vahid.sandoghdar@ethz.ch 1 arXiv:0707.3398v1 [quant-ph]

The transistor is one of the most influential inventions of modern times and is ubiquitous in present-day technologies. In the continuing development of increasingly powerful computers as well as alternative technologies based on the prospects of quantum information processing, switching and amplification functionalities are being sought in ultrasmall objects, such as nanotubes, molecules or atoms. Among the possible choices of signal carriers, photons are particularly attractive because of their robustness against decoherence, but their control at the nanometre scale poses a significant challenge as conventional nonlinear materials become ineffective. To remedy this shortcoming, resonances in optical emitters can be exploited, and atomic ensembles have been successfully used to mediate weak light beams. However, single-emitter manipulation of photonic signals has remained elusive and has only been studied in high-finesse microcavities or waveguides. Here we demonstrate that a single dye molecule can operate as an optical transistor and coherently attenuate or amplify a tightly focused laser beam, depending on the power of a second 'gating' beam that controls the degree of population inversion. Such a quantum optical transistor has also the potential for manipulating non-classical light fields down to the single-photon level. We discuss some of the hurdles along the road towards practical implementations, and their possible solutions.

Summary We developed an RNA sequencing-based pipeline to discover differentially expressed cell surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. Additionally, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2 directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target.

The radical S-adenosylmethionine (SAM) protein PqqE is predicted to function in the pyrroloquinoline quinone (PQQ) biosynthetic pathway via catalysis of carbon-carbon bond formation between a glutamate and tyrosine side chain within the small peptide substrate PqqA. We report here that PqqE activity is dependent on the accessory protein PqqD, which was recently shown to bind PqqA tightly. In addition, PqqE activity in vitro requires the presence of a flavodoxin-and flavodoxin reductasebased reduction system, with other reductants leading to an uncoupled cleavage of the co-substrate SAM. These results indicate that PqqE, in conjunction with PqqD, carries out the first step in PQQ biosynthesis: a radical-mediated formation of a new carbon-carbon bond between two amino acid side chains on PqqA.Pyrroloquinoline quinone (PQQ) 2 is employed by a wide variety of bacteria, where it functions as a redox cofactor in substrate oxidation via an alternate (non-glycolytic) pathway for production of cellular ATP (1). Hundreds of bacterial species are thought to produce PQQ, based on the presence in their genomes of the strongly conserved pqq operon (2) (Fig. 1A). Although the existence of this important redox cofactor has been known for decades, knowledge of the biosynthetic pathway for PQQ has remained scant (3, 4). The PQQ molecule derives from the evolutionarily conserved glutamate and tyrosine side chains within a ribosomally produced peptide substrate PqqA (Fig. 1, B and C). To produce PQQ, a large number of chemical modifications are required: (i) the formation of a new carbon-carbon bond between the ␥-carbon of glutamate and the 3-position of tyrosine (labeled in green in Fig. 1C); (ii) the addition of two additional hydroxyl groups to the tyrosine ring; (iii) a condensation between the 4-OH of tyrosine and the backbone amine of glutamate to produce a heterocyclic ring; and (iv) an 8-electron oxidation catalyzed by PqqC, a cofactorless enzyme that converts 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid (AHQQ) to PQQ in the final step of the pathway (5-7).The radical SAM enzyme PqqE has been the primary candidate as the catalyst for the formation of the new carbon-carbon bond between glutamate and tyrosine. Radical SAM proteins use the reductive cleavage of S-adenosyl methionine to initiate free radical chemistry, and can accomplish a wide variety of reactions, including carbon-carbon bond formation (8, 9). PqqE is a founding member of the SPASM domain-containing radical SAM proteins, which contain one or more auxiliary clusters in their C-terminal regions, and of which several are known to modify small peptides or proteins (10, 11). Recently, a small (ϳ10 kDa) protein, PqqD, has been shown to form a strong, sub-micromolar K D complex with the peptide substrate PqqA. This complex was further demonstrated to associate with PqqE (12). These findings suggested that PqqD would serve as a chaperone to deliver PqqA to PqqE, functioning as a necessary and heretofore missing componen...