54 research outputs found
Collaboration on reference to objects that are not mutually known
In conversation, a person sometimes has to refer to an object that is not
previously known to the other participant. We present a plan-based model of how
agents collaborate on reference of this sort. In making a reference, an agent
uses the most salient attributes of the referent. In understanding a reference,
an agent determines his confidence in its adequacy as a means of identifying
the referent. To collaborate, the agents use judgment, suggestion, and
elaboration moves to refashion an inadequate referring expression.Comment: 6 pages, to appear in proceedings of COLING-94, LaTeX (now uses
fullname.sty, fullname.bst
Antioxidant intervention in rheumatoid arthritis: results of an open pilot study
There is evidence that reactive oxygen species play a causal role in auto-immune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. To determine the potential beneficial effects of an antioxidant intervention on clinical parameters for RA, an open pilot study was designed. Eight non-smoking female patients with rheumatoid factor + RA and a Disease Activity Score (DAS 28) higher than 2.5 were enrolled in the study. Patients had to be receiving stable non-steroidal anti-inflammatory drug treatment and/or âsecond lineâ medication for at least 3Â months. The pilot group consumed 20Â g of antioxidant-enriched spread daily during a period of 10Â weeks. The intervention was stopped after 10Â weeks and was followed by a âwash-outâ period of 4Â weeks. At tâ=â0, tâ=â10Â weeks and tâ=â14Â weeks, patientsâ condition was assessed by means of DAS. In addition, standard laboratory analyses were performed, and blood-samples for antioxidants were taken. The antioxidant-enriched spread was well tolerated. All laboratory measures of inflammatory activity and oxidative modification were generally unchanged. However, the number of swollen and painful joints were significantly decreased and general health significantly increased, as reflected by a significantly improved (1.6) DAS at tâ=â10Â weeks. The antioxidant effect was considered beneficial as, compared to the scores at tâ=â0, the DAS significantly reduced at tâ=â10Â weeks. Increase of the DAS (0.7) after the âwash-out periodâ at tâ=â14 confirmed a causal relation between changes in clinical condition and antioxidants. This open pilot study aimed to assess the clinical relevance of an antioxidant intervention as a first step in assessing potential beneficial effects of antioxidants on rheumatoid arthritis. These conclusions need to be validated in a larger controlled study population
The Critical Juncture Conceptâs Evolving Capacity to Explain Policy Change
This article examines the evolution of our understanding of the critical junctures concept. The concept finds its origins in historical intuitionalism, being employed in the context of path dependence to account for sudden and jarring institutional or policy changes. We argue that the concept and the literature surrounding itânow incorporating ideas, discourse, and agencyâhave gradually become more comprehensive and nuanced as historical institutionalism was followed by ideational historical institutionalism and constructivist and discursive institutionalism. The prime position of contingency has been supplanted by the role of ideas and agency in explaining critical junctures and other instances of less than transformative change. Consequently, the concept is now capable of providing more comprehensive explanations for policy change
Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce ÎČ-chemokines
Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to âŒ10 ”g/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1α and MIP-1ÎČ. The release of these ÎČ-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes
Basic science232.âCertolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia Âź; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-ÎșB localization and IÎșB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-ÎșB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-ÎșB and degradation of IÎșB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-ÎșB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
Abstract COLLABORATION ON REFERENCE TO OBJECTS THAT ARE NOT MUTUALLY KNOWN
In conversation, a person sometimes has to refer to an object that is not previously known to the other participant. We present a plan-based model of how agents collaborate on reference of this sort. In making a reference, an agent uses the most salient attributes of the referent. In understanding a reference, an agent determines his confidence in its adequacy as a means of identifying the referent. To collaborate, the agents use judgment, suggestion, and elaboration moves to refashion an inadequate referring expression.
Extrauterine Mixed Mesodermal Tumors. An immunohistochemical Study.
Mixed mesodermal tumors are uncommon outside the uterus. Nine extrauterine mixed mesodermal tumors (eight ovarian and one extragenital) were selected for histochemical and immunoperoxidase study. In eight cases, both epithelial and mesenchymal elements were malignant (chondroid in six, rhabdomyoid in four, and osteoid in two). One ovarian tumor was an adenosarcoma. All cases were stained with periodic acid-Schiff with and without diastase and for alpha 1-antitrypsin, myoglobin, keratin, vimentin, muscle-specific actin, and alpha 1-antichymotrypsin, by using the avidin-biotin-immunoperoxidase method. The periodic acid-Schiff-positive, diastase-resistant droplets in several of the tumors showed peripheral alpha 1-antitrypsin positivity. Keratin delineated epithelial areas well in seven cases, and rhabdomyoid differentiation was confirmed with myoglobin in four cases. However, squamous elements in one tumor were falsely positive for myoglobin. We concluded that despite occasional cross-reactivity, carefully interpreted immunoperoxidase stains can be useful in distinguishing epithelial and mesenchymal elements in these tumors
Biosafety of Brucella abortus strain RB51 for vaccination of mature bulls and pregnant heifers
Objective - To determine shedding and colonization profiles in mature sexually intact bulls and pregnant heifers after vaccination with a standard calfhood dose of Brucella abortus strain RB51 (SRB51). Animals - 6 sexually mature 3-year-old Jersey bulls and 7 mixed-breed heifers in midgestation. Procedure - Bulls and pregnant heifers were vaccinated IM with the standard calfhood dose of 3 X 1010 colony-forming units of SRB51. After vaccination, selected body fluids were monitored weekly for vaccine organism shedding. Pathogenesis was monitored in bulls by weekly breeding soundness examination and, in heifers, by delivery status of the calf. Vaccine organism colonization was assessed by obtaining select tissue at necropsy for bacterial culture. Serologic analysis was performed by use of numerous tests, including complement fixation, an SRB51-based ELISA, and immunoblot analysis. Results - After vaccination, none of the vaccinated bulls or heifers shed SRB51 in their secretions. Results of breeding soundness examination for bulls were normal as was delivery status of the pregnant heifers (6 live births, 1 dystocia). At necropsy, SRB51 was not recovered from any of the selected tissues obtained from bulls, heifers, or calves; however, serologic analysis did detect SRB51-specific antibodies in all cattle. Conclusions and Clinical Relevance - Vaccination with the standard calfhood dose of SRB51 administered IM was not associated with shedding or colonization in sexually mature bulls or pregnant heifers. Also, under conditions of this study with small numbers of animals, IM vaccination with SRB51 does not appear to cause any reproductive problems when administered to sexually mature cattle
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