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6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate-biosynthetic pathway and is essential for microorganisms but absent from mammals. HPPK catalyzes Mg(2+)-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). Previously, three-dimensional structures of Escherichia coli HPPK (EcHPPK) have been determined at almost every stage of its catalytic cycle and the reaction mechanism has been established. Here, the crystal structure of Yersinia pestis HPPK (YpHPPK) in complex with HP and an ATP analog is presented together with thermodynamic and kinetic characterizations. The two HPPK molecules differ significantly in a helix-loop area (alpha2-Lp3). YpHPPK has lower affinities than EcHPPK for both nucleotides and HP, but its rate constants for the mechanistic steps of both chemical transformation and product release are comparable with those of EcHPPK. Y. pestis, which causes plague, is a category A select agent according to the Centers for Disease Control and Prevention (CDC). Therefore, these structural and biochemical data are valuable for the design of novel medical countermeasures against plague.

The making of the individual through social interaction was the subject of chapters 4 and 5. We have isolated a context in which a person was fashioned amidst the needs and ideas of a group, its assumptions, and social practices. Congruently, it has become clear that the social control produced by these institutions and practices was itself limited by the individual desires that stand at the heart of all disputes. None of those disagreements began from lofty first principles. They developed from recent, irritating, and personal problems.The so-called structures include both the force of the habitus (the collected predispositions of a social world) and the consequences of everyone’s individual choices and actions. As we have seen, these choices developed against the backdrop of hierarchy and differential public standing and they produced social selves of greatly varying scope and quality, inevitably made by converse with others.

In social history, actors without ideas are empty, just as ideas without actors are blind. This chapter tries to construct some of the cultural assumptions of the later medieval town in order to fill up some of its actors and give sight to its ideas.This attempt to examine part of the cultural habitus, to extract the common mind from nonlocal sources, requires only a little justification, for while we can never be sure without examination that ‘elite’ ideas have a direct and large impact on popular notions, historians have for a long time made important use of such materials. The social self demands it, for this is the concrete acknowledgment that consciousness matters, that people have ideas upon which they draw when making their decisions. This does not mean that there are not considerable difficulties in trying to determine what the sources tell us and how far we repeat the goals of the dominant in repeating their texts. But from Sylvia Thrupp through Rodney Hilton and Philippa Maddern to Fifteenth-Century Attitudes and Marjorie McIntosh’s Controlling Misbehavior in England, medieval historians have helped to display the mind of the matter in ways that allow us to see better what it all meant.1

The fraught character of premodern social life arose because little, if anything, came to you as your due, as certain, or just a matter of filing the appropriate papers and awaiting the check or the acclaim. People had no social rights. At every moment, the pursuit of legal claims, the establishment of power, and the protection of property was a social business requiring the support of others. Individual status was not certain, nor did a bureaucratic state apparatus neutrally process it. There was no such state, nor any other mechanism to separate the great mass of people from each other. You needed friends; you made enemies; and together these relations helped to define who you were as a social atom in the molecular structure of the town.Your connections to others and interventions on behalf of them were more important than we can easily imagine. We have already seen how complex medieval urban social interactions were.The records of arbitration and dispute settlement that we examine in chapters 3 and 4 start to make clear the extent to which people acted as each other’s brokers and abettors. We have seen how the manifold interests of individuals had to be balanced. Who you were in town was determined and reflected by your position in the structures of support that encapsulated your social actions. Nevertheless, certain eyes had a larger share in the creation of any social self. Your own perception was crucial, but also influential were those who watch you and act alongside you most often. Inevitably, the perceptions of the powerful would colonize you and you could rise and fall on their judgment.Whereas if they never saw you, you had almost no sociopolitical existence at all. To be a social being and a political animal was to be a member and a meaning to small groups of judges.

It has been a common feature of medieval urban histories to conclude, typically in an appendix, with brief notes on individuals, listing the bare bones of the documentary evidence. It was not always clear what the purpose of these was, possibly help to the local antiquarians keen on family history or for future biographers or prosopographers, with large computers and high hopes. Regardless of intention, it captured the essence of the social history of previous decades, in which the individual was something of an afterthought. At any rate, this chapter, a culmination of this book in many ways, is their descendant, bred, however, to take the individuals and the notions they lived by, more seriously. Yet, here is the problem from which we started: the difficulty of scraping up the medieval individual. The meaning of individual has now changed and become a kind of dialogue of self and world as the social self, but the problem remains and we should remind ourselves with the limiting case of Cecily Pontefract.

The three shepherds of the Wakefield “First Shepherds Play” are common men with common troubles.They are equals—like the small town and urban people we’re studying and who would have watched such plays—and that meant that their relative worth to each other shifted only gradually, but perhaps constantly. By contrast, the clear worthiness of Christ was simple for them, although they could see his surpassing quality in two ways, according to two schedules of honor, the worldly and the eternal. As they enter the stable and behold Him, the First Shepherd exclaims: “Hayll, King I thee call! Hayll, most of myght! Hayll, the worthyst of all. Hayll, duke! Hayll, knyght! Of greatt and small Thou art lorde by right…”l He speaks in the language of high class and power, of feudal rights, familiar things, precisely the things that shepherds did not have, but felt the butt end of. The Second Shepherd follows, however, with the great Christian irony: that Christ is but a baby and a humble one at that: “Hayll, little tyn’ mop, rewarder of mede! Hail, bot oone drop of grace at my nede; Hayll, lytytll mylk sop! Hayll, david sede! Of oure crede thou art crop; hayll, in god hede.”2 Odd as this might be to the canons of power, it is undoubtedly so, and known by all. How challenging a master view this is for social life however. These shepherds must assess the child’s status and that means their own relative status. They are given a great advantage: the angels have already explained the situation, but furthermore, Christ is outside their normal domain, from another social circle entirely. From either the spiritual or political perspective He is worthiest and of another kind. Here is class difference of the first magnitude.

Much more than we can imagine today, medieval people were almost overwhelmed by a social world that rarely left them alone. Every individual faced an idiosyncratic collection of social pressures. Medieval townspeople had no fewer social pressures than peasants in their village communities. For the privileged urban burgesses or citizens—those men who had chosen to enroll in the Borough Community of their town or city, to pay its taxes and have its privileges—their fraternity was an important high-pressure and high profile glass tank. It is a very good one through which to see the mingling of group and individual. But since the game to which people subscribe was, like language, not of their own creation, this chapter tries to show how such groups might press upon their members, bending them all, if breaking only a few.1 It did so at every step by invoking and strengthening the master values of fidelity, honor, and hierarchical order upon which the justification for social action and social control rested.

To understand the significance of the life narratives in chapter 8 is to see that agency exists even when nothing of “importance” happens. It is really an effect of a mind. It is the place of meaning, not only of action. It belongs to the politically and the economically insignificant person as surely at to the powerful. Action itself, the great business that needs explanation, is intelligible only in the boundaries of meaning, in the domain of petty intentions and failures. Part of the job of history is to render embodied meaning in all its manifestations; it is to understand the human situation—all its probable potential—in a historical moment.The social self is a cultural complex, a category that enables our understanding by drawing social history and agency together. It is a powerful aide to seeing the “structuration”—in Giddens’ sense—of the world, of self and society, body and idea, person and person.

Maurice Keen reestablished the dignity of chivalry as part of medieval history with his vivid, wise masterpiece Chivalry [1984], and since then new vigor has filled the study of aristocratic cultur...

Infections frequently cause or complicate illnesses associated with hypoxaemia and local tissue hypoxia. The influence of hypoxia on the interaction between host and pathogen is therefore of considerable interest. S. aureus is a major pathogen in critical care where patients may have profound hypoxaemia and at a tissue level, S. aureus frequently infects ischaemic wounds. We investigated the effect of systemic hypoxia on host-pathogen interactions using a subcutaneous S. aureus infection model in mice. C57BL/6 mice were shaved, injected with a low dose of S. aureus (5x107 SH1000) and placed in a hypoxic chamber (10% O2) or left in room air. At 6 or 12 hours mice were assessed clinically and rectal temperature recorded. Clinical assessment of mouse sickness behaviour was made by two independent observers blinded as to which oxygen tension the mice had been exposed. Mice were anaesthetised and tissue samples (blood, skin, lung, spleen, kidney, liver and brain) obtained for analysis. Mice injected with live bacteria and placed in hypoxia developed a phenotype of sickness behaviour and hypothermia. Infected hypoxic mice had significantly higher sickness scores and lower body temperature than infected normoxic mice or hypoxic mice injected with PBS (rectal temperature at 12 hours: hypoxic 33.4˚C ± 0.74, normoxic 37.7˚C ± 0.24, hypoxic PBS-injected 38.9˚C ± 0.26, p These findings imply that hypoxia may adversely alter the host response to a minor bacterial challenge, leading to profound systemic illness and that in such a setting modulation of the HIF pathway may be a possible therapeutic option.

Permission to copy is restricted to an abstract of not more than 300 words. Illustrations may not be copied. The abstract should contain conspicuous acknowledgment of where and by whom the paper is presented. Publication elsewhere is usually granted upon request provided proper credit is made. Abstract The Petrojarl I is the first purpose-built floating production and extended well test ship designed for worldwide application under the same type of leasing arrangement as a floating drilling rig. All other floating production systems in operation today are designed for site-specific conditions and would require significant modification for other applications. In its present: configuration this turret-moored process plant/storage tanker receives production from a single subsea well via either rigid or flexible risers. Stabilized crude is exported by an off-loading system to a shuttle tanker. This paper reviews the manufacture, testing, installation and early operating experience for the subsea production equipment associated with the Petrojarl I Production/Test Ship (PTS). It provides an overview of the system together with some of the more important design parameters. It also recounts the actual manufacturing, testing, installation and early operating experience for the subsea and other critical systems. This new type of production system is seen to be technically feasible and is also proving to be an economic success even in current depressed market conditions. BACKGROUND AND SYSTEMS DESCRIPTION Golar Nor Offshore A/S first placed contracts for the construction of the production/test ship (PTS) Petrojarl I in June of 1984. The PTS would be offered to the world market on a charter basis for the following applications:Conducting extended well tests to enhance reservoir evaluation for better depletion strategies by the permanent production facilities. For this purpose the system must be fully capable of wireline operations as well as production flow testing. Depending on production rates the oil produced can partially or fully defray the cost of this extended evaluation.