B cells are not essential for peripheral T-cell tolerance.

Some self-reactive T cells avoid thymic tolerance and become mature peripheral cells. Nevertheless, these cells do not usually attack their hosts because T cells can be inactivated or killed, even after they are mature, by various means. The details of these processes are not fully understood; however, a number of experiments have suggested that peripheral tolerance may be induced in mature mouse T cells by exposure to antigen on resting B cells, cells that can express antigen bound to major histocompatibility complex proteins but that lack critical costimulatory molecules such as B7-1 and B7-2. Conversely, previous experiments have indicated that mature T cells can be stimulated by exposure to antigen on cells such as dendritic cells, cells that are thought to express the essential costimulatory molecules. We tested this idea in vivo by using mice that lack B cells. Unexpectedly, T-cell tolerance and antigen-induced T-cell death occurred normally in mice free of B cells. On the other hand, antigen-specific T-cell expansion in the spleens of such mice was impaired. Finally, we have recently shown that T-cell death in mice can be prevented by exposure to antigen and an inflammatory agent such as bacterial lipopolysaccharide. This was also true in mice that lacked B cells. Overall, these data show that mature T cells can be tolerized and rescued from tolerance in the absence of B cells.

FAS is highly expressed in the germinal center but is not required for regulation of the B-cell response to antigen.

In establishing the memory B-cell population and maintaining self-tolerance during an immune response, apoptosis mediates the removal of early, low-affinity antibody-forming cells, unselected germinal center (GC) cells, and, potentially, self-reactive B cells. To address the role of the apoptosis-signaling cell surface molecule FAS in the B-cell response to antigen, we have examined the T-cell-dependent B-cell response to the carrier-conjugated hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) in lpr mice in which the fas gene is mutated. High levels of FAS were expressed on normal GC B cells but the absence of FAS did not perturb the progressive decline in numbers of either GC B cells or extrafollicular antibody-forming cells. Furthermore, the rate of formation and eventual size of the NP-specific memory B-cell population in lpr mice were normal. The accumulation of cells with affinity-enhancing mutations and the appearance of high-affinity anti-NP IgG1 antibody in the serum were also normal in lpr mice. Thus, although high levels of FAS are expressed on GC B cells, FAS is not required for GC selection or for regulation of the major antigen-specific B-cell compartments. The results suggest that the size and composition of B-cell compartments in the humoral immune response are regulated by mechanisms that do not require FAS.

The N-terminal region (A/B) of rat thyroid hormone receptors alpha 1, beta 1, but not beta 2 contains a strong thyroid hormone-dependent transactivation function.

In this study we have investigated the role of the N-terminal region of thyroid hormone receptors (TRs) in thyroid hormone (TH)-dependent transactivation of a thymidine kinase promoter containing TH response elements composed either of a direct repeat or an inverted palindrome. Comparison of rat TR beta 1 with TR beta 2 provides an excellent model since they share identical sequences except for their N termini. Our results show that TR beta 2 is an inefficient TH-dependent transcriptional activator. The degree of transactivation corresponds to that observed for the mutant TR delta N beta 1/2, which contains only those sequences common to TR beta 1 and TR beta 2. Thus, TH-dependent activation appears to be associated with two separate domains. The more important region, however, is embedded in the N-terminal domain. Furthermore, the transactivating property of TR alpha 1 was also localized to the N-terminal domain between amino acids 19 and 30. Using a coimmunoprecipitation assay, we show that the differential interaction of the N terminus of TR beta 1 and TR beta 2 with transcription factor IIB correlates with the TR beta 1 activation function. Hence, our results underscore the importance of the N-terminal region of TRs in TH-dependent transactivation and suggest that a transactivating signal is transmitted to the general transcriptional machinery via a direct interaction of the receptor N-terminal region with transcription factor IIB.

Age estimations of calcareous nannofossil biohorizons of the middle Paleocene to early Eocene at ODP Site 208-1262 (Table 1, Appendix B)

Over the last several decades debates on the 'tempo and mode' of evolution have centered on the question whether morphological evolution preferentially occurs gradually or punctuated, i.e., with long periods of stasis alternating with short periods of rapid morphological change and generation of new species. Another major debate is focused on the question whether long-term evolution is driven by, or at least strongly influenced by changes in the environment, or by interaction with other life forms. Microfossils offer a unique opportunity to obtain the large datasets as well as the precision in dating of subsequent samples to study both these questions.We present high-resolution analyses of selected calcareous nannofossils from the deep-sea section recovered at ODP Site 1262 (Leg 208) in the South-eastern Atlantic. The studied section encompasses nannofossil Zones NP4-NP12 (equivalent to CP3-CP10) and Chrons C27r-C24n. We document more than 70 biohorizons occurring over an about 10 Myr time interval, (~62.5 Ma to ~52.5 Ma), and discuss their reliability and reproducibility with respect to previous data, thus providing an improved biostratigraphic framework, which we relate to magnetostratigraphic information, and present for two possible options of a new Paleocene stratigraphic framework based on cyclostratigraphy. This new framework enabled us to tentatively reconstruct steps in the evolution of early Paleogene calcareous nannoplankton through documentation of transitional morphotypes between genera and/or species and of the phylogenetic relations between the genera Fasciculithus, Heliolithus, Discoasteroides and Discoaster, as well as between Rhomboaster and Tribrachiatus. The exceptional record provided by the continuous, composite sequence recovered at Walvis Ridge allows us to describe the mode of evolution among calcareous nannoplankton: new genera and/or new species usually originated through branching of lineages via gradual, but relatively rapid, morphological transitions, as documented by the presence of intermediate forms between the end-member ancestral and descendant forms. Significant modifications in the calcareous nannofossil assemblages are often "related" to significant changes in environmental conditions, but the appearance of structural innovations and radiations within a single genus also occurred during "stable" environmental conditions. These lines of evidence suggest that nannoplankton evolution is not always directly triggered by stressed environmental conditions but could be also driven by endogenous biotic control.

The law of charitable uses, rev. and much enl.; with many cases in law both antient and modern: whereunto is now added,the learned reading of Sr Francis Moor, Kt. ... upon the statute of 43 Eliz. concerning charitable uses, (who was a member of that Parliament when that statute was made, and the penner thereof.) Abridged by himself, and now printed by his own original manuscript. Together, with the manner of proceedings in Chancery, by information, in the name of the King's attorney-general, for relief, on divers cases, wherein the aid of this statute is not required ... Methodically digested,

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A new treatise on French pronunciation, or, a series of rules : by which every person acquainted with the English language, may readily ascertain the French pronunciation of all words, even those which do not belong to the French language / B.F. Bugard.

Mode of access: Internet.

Essays and reviews of George Eliot not hitherto reprinted; together with an introductory essay on the genius of George Eliot by Mrs. S. B. Herrick.

Mode of access: Internet.

Random error in willingness to pay measurement: A multiple indicators, latent variable approach to the reliability of contingent values

The reliability of measurement refers to unsystematic error in observed responses. Investigations of the prevalence of random error in stated estimates of willingness to pay (WTP) are important to an understanding of why tests of validity in CV can fail. However, published reliability studies have tended to adopt empirical methods that have practical and conceptual limitations when applied to WTP responses. This contention is supported in a review of contingent valuation reliability studies that demonstrate important limitations of existing approaches to WTP reliability. It is argued that empirical assessments of the reliability of contingent values may be better dealt with by using multiple indicators to measure the latent WTP distribution. This latent variable approach is demonstrated with data obtained from a WTP study for stormwater pollution abatement. Attitude variables were employed as a way of assessing the reliability of open-ended WTP (with benchmarked payment cards) for stormwater pollution abatement. The results indicated that participants' decisions to pay were reliably measured, but not the magnitude of the WTP bids. This finding highlights the need to better discern what is actually being measured in VVTP studies, (C) 2003 Elsevier B.V. All rights reserved.

T cells signaled by NF-kappa B- dendritic cells are sensitized not anergic to subsequent activation

Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the presence of an NF-kappaB inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC), generated in the presence of an NF-kappaB inhibitor, signal phosphorylation of TCRzeta, but little proliferation or IFN-gamma in vitro. Proliferation is arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-gamma production. The data indicate that signaling through NF-kappaB determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappaB(-)CD40(-)class II+ DC may either tolerize or sensitize T cells. Thus, while CD40(-) DC appear to prime or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.

High-fidelity Z-measurement error encoding of optical qubits

We demonstrate a quantum error correction scheme that protects against accidental measurement, using a parity encoding where the logical state of a single qubit is encoded into two physical qubits using a nondeterministic photonic controlled-NOT gate. For the single qubit input states vertical bar 0 >, vertical bar 1 >, vertical bar 0 > +/- vertical bar 1 >, and vertical bar 0 > +/- i vertical bar 1 > our encoder produces the appropriate two-qubit encoded state with an average fidelity of 0.88 +/- 0.03 and the single qubit decoded states have an average fidelity of 0.93 +/- 0.05 with the original state. We are able to decode the two-qubit state (up to a bit flip) by performing a measurement on one of the qubits in the logical basis; we find that the 64 one-qubit decoded states arising from 16 real and imaginary single-qubit superposition inputs have an average fidelity of 0.96 +/- 0.03.