Evidence for somatic selection of natural autoantibodies.

Natural autoantibodies are primarily immunoglobulin M (IgM) antibodies that bind to a variety of self-antigens, including self-IgG. Accounting for a large proportion of the early B cell repertoire, such polyspecific autoantibodies are speculated to contribute to the homeostasis and/or competence of the primary humoral immune system. Recent studies indicate that the leukemia cells from most patients with chronic lymphocytic leukemia (CLL) also express such IgM autoantibodies. Similarly, the leukemia cells from many CLL patients react with murine monoclonal antibodies (mAbs) specific for crossreactive idiotypes (CRIs) associated with human IgM autoantibodies. In particular, leukemic cells frequently react with G6, a mAb specific for an Ig heavy chain (H chain)-associated CRI, and/or with 17.109, a mAb that defines a kappa light chain (L chain)-associated CRI. Generated against IgM rheumatoid factor (RF) paraproteins, G6 and 17.109 each recognize a major CRI that is present in many IgM RF paraproteins. Furthermore, over 90% of the IgM paraproteins found to bear both H and L chain-associated CRIs also are found to have RF activity. Molecular characterization of these CRIs demonstrates that each is a serologic marker for expression of a highly conserved Ig V gene. As such, the frequent production of IgM polyspecific autoantibodies in CLL simply may reflect the frequent use of such highly conserved autoantibody-encoding Ig V genes with little or no somatic mutation. To test this hypothesis, we generated murine transfectomas to pair the 17.109-reactive kappa L chain of SMI, a 17.109/G6-reactive CLL population, with the Ig H chain of SMI or other G6-reactive leukemia cells or tonsillar lymphocytes. Cotransfection of vectors encoding the Ig H and L chains of SMI generated transfectomas that produce IgM kappa RF autoantibodies reactive with human IgG1 and IgG4. In contrast to G6/17.109-reactive IgM kappa RF Waldenstrom's paraproteins, the SMI IgM kappa also reacts with several other self-antigens, including myoglobin, actin, and ssDNA. However, cotransfection of the SMI L chain with a vector encoding any one of 10 different G6-reactive Ig H chains generated transfectomas that produce IgM kappa antibodies without detectable polyspecific autoantibody activity. These results indicate that polyspecific antiself-reactivity of G6/17.019-reactive Ig is dependent on the somatically generated Ig third complementarity determining region. Collectively, these studies imply that selection may be responsible for the frequent expression of polyspecific autoantibodies in CLL and early B cell ontogeny

Public infrastructure and regional economic development: a simultaneous equations approach

A study of how public capital stock impacts regional economic development, which jointly models the effects of local public infrastructure on personal income and the effect of personal income on the allocation of local public outlays.Infrastructure (Economics) ; Regional economics ; Income

The design co-ordination framework : key elements for effective product development

This paper proposes a Design Co-ordination Framework (DCF) i.e. a concept for an ideal DC system with the abilities to support co-ordination of various complex aspects of product development. A set of frames, modelling key elements of co-ordination, which reflect the states of design, plans, organisation, allocations, tasks etc. during the design process, has been identified. Each frame is explained and the co-ordination, i.e. the management of the links between these frames, is presented, based upon characteristic DC situations in industry. It is concluded that while the DCF provides a basis for our research efforts into enhancing the product development process there is still considerable work and development required before it can adequately reflect and support Design Co-ordination

“The Slow Creep of Complacency”: Ongoing Challenges for Democracies Seeking to Detain Terrorism Suspects

This article assesses shifting presumptions by three democracies -- the United States, Canada, and the United Kingdom – all of whom appear to have permanently adopted some alterations to their detention practices for certain terrorism-related cases since the attacks of September 11, 2001 (hereinafter “9/11”). A review of executive, legislative and judicial outcomes in these three countries often reveals an ongoing tension between the judiciary and the other branches of government, with the judiciary frequently citing to traditional constitutional principles to reassert the primacy of individual liberties and fair trial guarantees. In spite of such rulings, however, the advance towards some system of preventive detention and abridged judicial process for terrorism suspects continues, in various forms, in each of these countries. It appears that this ongoing tension between some national high courts and political branches of government may be based, in part, on the judicial role of safeguarding constitutional protections, while the other branches have increasingly become reliant upon a form of discourse that may be at odds with those principles, and much of which was developed in a time of perceived emergency. The premises on which detention practices have been altered may not have been fully assessed in the years after 9/11 by those in policy-making positions. This ongoing tension and continuing uncertainty as to the status of certain constitutional protections may have larger implications for the viability of long-standing constitutional norms, as well as for larger criminal-justice standards, and those implications must be further examined before any such changes do, indeed, become permanent

Independent Orbiter Assessment (IOA): Analysis of the atmospheric revitalization pressure control subsystem

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis/Critical Items List (FMEA/CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results corresponding to the Orbiter Atmospheric Revitalization and Pressure Control Subsystem (ARPCS) are documented. The ARPCS hardware was categorized into the following subdivisions: (1) Atmospheric Make-up and Control (including the Auxiliary Oxygen Assembly, Oxygen Assembly, and Nitrogen Assembly); and (2) Atmospheric Vent and Control (including the Positive Relief Vent Assembly, Negative Relief Vent Assembly, and Cabin Vent Assembly). The IOA analysis process utilized available ARPCS hardware drawings and schematics for defining hardware assemblies, components, and hardware items. Each level of hardware was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode

Buoyancy-driven inflow to a relic cold core: the gas belt in radio galaxy 3C 386

We report measurements from an XMM-Newton observation of the low-excitation radio galaxy 3C 386. The study focusses on an X-ray-emitting gas belt, which lies between and orthogonal to the radio lobes of 3C 386 and has a mean temperature of $0.94\pm0.05$ keV, cooler than the extended group atmosphere. The gas in the belt shows temperature structure with material closer to the surrounding medium being hotter than gas closer to the host galaxy. We suggest that this gas belt involves a `buoyancy-driven inflow' of part of the group-gas atmosphere where the buoyant rise of the radio lobes through the ambient medium has directed an inflow towards the relic cold core of the group. Inverse-Compton emission from the radio lobes is detected at a level consistent with a slight suppression of the magnetic field below the equipartition value.Comment: 11 pages, 10 figures, accepted for publication in MNRA

Rotation symmetry axes and the quality index in a 3D octahedral parallel robot manipulator system

The geometry of a 3D octahedral parallel robot manipulator system is specified in terms of two rigid octahedral structures (the fixed and moving platforms) and six actuation legs. The symmetry of the system is exploited to determine the behaviour of (a new version of) the quality index for various motions. The main results are presented graphically