271 research outputs found
Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]
Background
Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS).
Methods
The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance.
Results
There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype.
Conclusions
We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases
A Monitor of Beam Polarization Profiles for the TRIUMF Parity Experiment
TRIUMF experiment E497 is a study of parity violation in pp scattering at an
energy where the leading term in the analyzing power is expected to vanish,
thus measuring a unique combination of weak-interaction flavour conserving
terms. It is desired to reach a level of sensitivity of 2x10^-8 in both
statistical and systematic errors. The leading systematic errors depend on
transverse polarization components and, at least, the first moment of
transverse polarization. A novel polarimeter that measures profiles of both
transverse components of polarization as a function of position is described.Comment: 19 pages LaTeX, 10 PostScript figures. To appear in Nuclear
Instruments and Methods in Physics Research, Section
Influence of Fabrication Technique on the Fiber Pushout Behavior in a Sapphire-Reinforced Nial Matrix Composite
Directional solidification (DS) of \u27\u27powder-cloth\u27\u27 (PC) processed sapphire-NiAl composites was carried out to examine the influence of fabrication technique on the fiber-matrix interfacial shear strength, measured using a fiber-pushout technique. The DS process replaced the fine, equiaxed NiAl grain structure of the PC composites with an oriented grain structure comprised of large columnar NiAl grains aligned parallel to the fiber axis, with fibers either completely engulfed within the NiAl grains or anchored at one to three grain boundaries. The load-displacement behavior during the pushout test exhibited an initial \u27\u27pseudoelastic\u27\u27 response, followed by an \u27\u27inelastic\u27\u27 response, and finally a \u27\u27frictional\u27\u27 sliding response. The fiber-matrix interfacial shear strength and the fracture behavior during fiber pushout were investigated using an interrupted pushout test and fractography, as functions of specimen thickness (240 to 730 mu m) and fabrication technique. The composites fabricated using the PC and the DS techniques had different matrix and interface structures and appreciably different interfacial shear strengths. In the DS composites, where the fiber-matrix interfaces were identical for all the fibers, the interfacial debond shear stresses were larger for the fibers embedded completely within the NiAl grains and smaller for the fibers anchored at a few grain boundaries. The matrix grain boundaries coincident on sapphire fibers were observed to be the preferred sites for crack formation and propagation. While the frictional sliding stress appeared to be independent of the fabrication technique, the interfacial debond shear stresses were larger for the DS composites compared to the PC composites. The study highlights the potential of the DS technique to grow single-crystal NiAl matrix composites reinforced with sapphire fibers, with fiber-matrix interfacial shear strength appreciably greater than that attainable by the current solid-state fabrication techniques
Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.
Extensive transcriptional and ontogenetic diversity exists among normal tissue-resident macrophages, with unique transcriptional profiles endowing the cells with tissue-specific functions. However, it is unknown whether the origins of different macrophage populations affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone-marrow-derived macrophages (BMDMs) are present in tumors of the brain, a tissue with no homeostatic involvement of BMDMs. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing to demonstrate that BMDMs are abundant in primary and metastatic brain tumors. Our data indicate that distinct transcriptional networks in brain-resident microglia and recruited BMDMs are associated with tumor-mediated education yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between microglia and BMDMs in primary and metastatic disease in mouse and human
Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells
Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease. We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and spatial tissue characterization. This revealed disease-specific enrichment of immune cells with pronounced differences in proportional abundance of tissue-resident microglia, infiltrating monocyte-derived macrophages, neutrophils, and T cells. These integrated analyses also uncovered multifaceted immune cell activation within brain malignancies entailing converging transcriptional trajectories while maintaining disease- and cell-type-specific programs. Given the interest in developing TME-targeted therapies for brain malignancies, this comprehensive resource of the immune landscape offers insights into possible strategies to overcome tumor-supporting TME properties and instead harness the TME to fight cancer
Parity Violation in Proton-Proton Scattering
Measurements of parity-violating longitudinal analyzing powers (normalized
asymmetries) in polarized proton-proton scattering provide a unique window on
the interplay between the weak and strong interactions between and within
hadrons. Several new proton-proton parity violation experiments are presently
either being performed or are being prepared for execution in the near future:
at TRIUMF at 221 MeV and 450 MeV and at COSY (Kernforschungsanlage Juelich) at
230 MeV and near 1.3 GeV. These experiments are intended to provide stringent
constraints on the set of six effective weak meson-nucleon coupling constants,
which characterize the weak interaction between hadrons in the energy domain
where meson exchange models provide an appropriate description. The 221 MeV is
unique in that it selects a single transition amplitude (3P2-1D2) and
consequently constrains the weak meson-nucleon coupling constant h_rho{pp}. The
TRIUMF 221 MeV proton-proton parity violation experiment is described in some
detail. A preliminary result for the longitudinal analyzing power is Az = (1.1
+/-0.4 +/-0.4) x 10^-7. Further proton-proton parity violation experiments are
commented on. The anomaly at 6 GeV/c requires that a new multi-GeV
proton-proton parity violation experiment be performed.Comment: 13 Pages LaTeX, 5 PostScript figures, uses espcrc1.sty. Invited talk
at QULEN97, International Conference on Quark Lepton Nuclear Physics --
Nonperturbative QCD Hadron Physics & Electroweak Nuclear Processes --, Osaka,
Japan May 20--23, 199
Isospin Effects in Nuclear Multifragmentation
We develop an improved Statistical Multifragmentation Model that provides the
capability to calculate calorimetric and isotopic observables with precision.
With this new model we examine the influence of nuclear isospin on the fragment
elemental and isotopic distributions. We show that the proposed improvements on
the model are essential for studying isospin effects in nuclear
multifragmentation. In particular, these calculations show that accurate
comparisons to experimental data require that the nuclear masses, free energies
and secondary decay must be handled with higher precision than many current
models accord.Comment: 46 pages, 16 figure
Excitation and decay of projectile-like fragments formed in dissipative peripheral collisions at intermediate energies
Projectile-like fragments (PLF:15<=Z<=46) formed in peripheral and
mid-peripheral collisions of 114Cd projectiles with 92Mo nuclei at E/A=50 MeV
have been detected at very forward angles, 2.1 deg.<=theta_lab<=4.2 deg.
Calorimetric analysis of the charged particles observed in coincidence with the
PLF reveals that the excitation of the primary PLF is strongly related to its
velocity damping. Furthermore, for a given V_PLF*, its excitation is not
related to its size, Z_PLF*. For the largest velocity damping, the excitation
energy attained is large, approximately commensurate with a system at the
limiting temperatureComment: 5 pages, 6 figure
Parity Violation in Proton-Proton Scattering at 221 MeV
TRIUMF experiment 497 has measured the parity violating longitudinal
analyzing power, A_z, in pp elastic scattering at 221.3 MeV incident proton
energy. This paper includes details of the corrections, some of magnitude
comparable to A_z itself, required to arrive at the final result. The largest
correction was for the effects of first moments of transverse polarization. The
addition of the result, A_z=(0.84 \pm 0.29 (stat.) \pm 0.17 (syst.)) \times
10^{-7}, to the pp parity violation experimental data base greatly improves the
experimental constraints on the weak meson-nucleon coupling constants
h^{pp}_\rho and h^{pp}_\omega, and has implications for the interpretation of
electron parity violation experiments.Comment: 17 pages RevTeX, 14 PostScript figures. Revised version with
additions suggested by Phys. Rev.
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