1 RT ± PCR-southern hybridization analyses with radiolabelled P2Y receptor cDNAs as probes indicated that the peripheral blood leukocytes and the human umbilical vein endothelial cells express P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 receptors.

Screening of a human erythroleukemia cell cDNA library with radiolabeled chicken P2Y 3 cDNA at low stringency revealed a cDNA clone encoding a novel G protein-coupled receptor with homology to P2 purinoceptors. This receptor, designated P2Y 7 , has 352 amino acids and shares 23-30% amino acid identity with the P2Y 1 -P2Y 6 purinoceptors. The P2Y 7 cDNA was transiently expressed in COS-7 cells: binding studies thereon showed a very high affinity for ATP (37 ؎ 6 nM), much less for UTP and ADP (ϳ1300 nM), and a novel rank order of affinities in the binding series studied of 8 nucleotides and suramin. The P2Y 7 receptor sequence appears to denote a different subfamily from that of all the other known P2Y purinoceptors, with only a few of their characteristic sequence motifs shared. The P2Y 7 receptor mRNA is abundantly present in the human heart and the skeletal muscle, moderately in the brain and liver, but not in the other tissues tested. The P2Y 7 receptor mRNA was also abundantly present in the rat heart and cultured neonatal rat cardiomyocytes. The P2Y 7 receptor is functionally coupled to phospholipase C in COS-7 cells transiently expressing this receptor. The P2Y 7 gene was shown to be localized to human chromosome 14. We have thus cloned a unique member of the P2Y purinoceptor family which probably plays a role in the regulation of cardiac muscle contraction.The widespread occurrence of metabotropic receptors for extracellular ATP has long been inferred from physiological and pharmacological evidence (1). A number of such G proteincoupled ATP receptors have been characterized and a consensus on their nomenclature has termed all of these as P2Y purinoceptors (to be individually named P2Y 1 to P2Y n ), regardless of previous terminology such as P 2U or P 2T for subclasses thereof (2). The first such receptors to be characterized by DNA cloning and expression were the P2Y 1 receptor (where UTP is inactive) (3) and the P2Y 2 receptor (ATP and UTP are equally active) (4). True species homologues (or orthologues) of P2Y 1 have since been obtained, e.g. bovine (5) and human (6), and of P2Y 2 , e.g. from human airway epithelium (7) or human erythroleukemia (HEL) 1 cells (8). Further types identified by cloning have been the P2Y 3 receptor (UDP Ͼ ADP Ͼ ATP) (9) and P2Y 4 (UTP Ͼ Ͼ ATP, and more strongly related to P2Y 2 ) (10, 11). Further novel P2Y receptors have recently been identified from their cDNAs from chicken activated T lymphocytes (12) and rat vascular smooth muscle cells (13) and designated P2Y 5 and P2Y 6 receptors. Previously we have demonstrated at least three P2 purinoceptors on the hematopoietic cell line, HEL cells, by intracellular calcium mobilization and by photoaffinity labeling (8). Here we report the molecular cloning and characterization of one of these, a novel P2 purinergic receptor designated P2Y 7 .

Previously we defined binding sites for high molecular weight kininogen (HK) and thrombin in the Apple 1 (A1) domain of factor XI (FXI). Since prothrombin (and Ca(2+)) can bind FXI and can substitute for HK (and Zn(2+)) as a cofactor for FXI binding to platelets, we have attempted to identify a prothrombin-binding site in FXI. The recombinant A1 domain (rA1, Glu(1)-Ser(90)) inhibited the saturable, specific and reversible binding of prothrombin to FXI, whereas neither the rA2 domain (Ser(90)-Ala(181)), rA3 domain (Ala(181)-Val(271)), nor rA4 domain (Phe(272)-Glu(361)) inhibited prothrombin binding to FXI. Kinetic binding studies using surface plasmon resonance showed binding of FXI (K(d) approximately 71 nm) and the rA1 domain (K(d) approximately 239 nm) but not rA2, rA3, or rA4 to immobilized prothrombin. Reciprocal binding studies revealed that synthetic peptides (encompassing residues Ala(45)-Ser(86)) containing both HK- and thrombin-binding sites, inhibit (125)I-rA1 (Glu(1)-Ser(90)) binding to prothrombin, (125)I-prothrombin binding to FXI, and (125)I-prothrombin fragment 2 (Ser(156)-Arg(271)) binding to FXI. However, homologous prekallikrein-derived peptides (encompassing Pro(45)-Gly(86)) did not inhibit FXI rA1 binding to prothrombin. The peptides Ala(45)-Arg(54), Phe(56)-Val(71), and Asp(72)-Ser(86), derived from sequences of the A1 domain of FXI, acted synergistically to inhibit (125)I-rA1 binding to prothrombin. Mutant rA1 peptides (V64A and I77A), which did not inhibit FXI binding to HK, retained full capacity to inhibit rA1 domain binding to prothrombin, and mutant rA1 peptides Ala(45)-Ala(54) (D51A) and Val(59)-Arg(70) (E66A), which did not inhibit FXI binding to thrombin, retained full capacity to inhibit rA1 domain binding to prothrombin. Thus, these experiments demonstrate that a prothrombin binding site exists in the A1 domain of FXI spanning residues Ala(45)-Ser(86) that is contiguous with but separate and distinct from the HK- and thrombin-binding sites and that this interaction occurs through the kringle II domain of prothrombin.

Quantum networks must classically exchange complex metadata between devices in order to carry out information for protocols such as teleportation, super-dense coding, and quantum key distribution. Demonstrating the integration of these new communication methods with existing network protocols, channels, and data forwarding mechanisms remains an open challenge. Software-defined networking (SDN) offers robust and flexible strategies for managing diverse network devices and uses. We adapt the principles of SDN to the deployment of quantum networks, which are composed from unique devices that operate according to the laws of quantum mechanics. We show how quantum metadata can be managed within a software-defined network using the OpenFlow protocol, and we describe how OpenFlow management of classical optical channels is compatible with emerging quantum communication protocols. We next give an example specification of the metadata needed to manage and control QPHY behavior and we extend the OpenFlow interface to accommodate this quantum metadata. We conclude by discussing near-term experimental efforts that can realize SDN's principles for quantum communication.Quantum information theory promises a variety of new techniques for transmitting, protecting, and processing information that may benefit the efficiency, security, and speed of tactical communication networks. This includes higher bandwidth encodings on network links, idealized encryption between network nodes, and faster, distributed computation across the network topology. These capabilities could offer disruptive advances in military communication networks. However, quantum information theory also imposes constraints on the operation of a quantum network including, for example, nocloning and no-broadcasting. Therefore, conventional network engineering methods are unlikely to apply to the construction of future quantum networks, and new methods for quantum network engineering and management are needed to address different use cases. While multiple experimental demonstrations have validated these ideas, demonstrating the integration of quantum communication methods with existing protocols, channels, and data forwarding mechanisms is an open challenge.Software-defined networking (SDN) is an emerging and fast growing technology for interconnecting network devices and forwarding packets based on unified policies and security enforcements. SDN capabilities have also been recently highlighted as an important enabling capability for military tactical networks, where assured networking is critical and flexible management are needed. The defining feature of SDN is deep programmability of the network at all layers including the extension of the network state into applications for enabling better pathing decisions. This versatile and programmable network architecture is expected to be more suitable to support future heterogeneous systems and implement ad hoc network policies, for example, that may arise in tactical environments. This includes quantum communication model...

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