| 1. |
- Schael, S, et al.
(författare)
-
Precision electroweak measurements on the Z resonance
- 2006
-
Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
-
Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Tacon, Lyndal J., et al.
(författare)
-
The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors
- 2009
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:11, s. 4591-4599
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. The Weiss score is the most widely accepted method for distinguishing an ACC from an adrenocortical adenoma (ACA); however, in borderline cases, accurate diagnosis remains problematic. We recently discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly up-regulated in ACCs compared with ACAs in global gene expression studies. OBJECTIVE: Our objective was to study GR expression in adrenocortical tumors (ACTs) and to assess its utility as an adjunct to the Weiss score. DESIGN: Microarray analysis, real-time quantitative RT-PCR (qPCR), immunohistochemistry, Western blot, and direct sequencing were performed. RESULTS: Analysis of 28 ACTs by microarray and 49 ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the presence of the GRalpha isoform in ACCs, and no mutations were detected on direct sequencing. Immunohistochemistry for GR in an overlapping cohort of ACTs demonstrated strongly positive nuclear staining in 31 of 33 ACCs (94%), with negative staining in 40 of 41 ACAs (98%) (P < 0.001). This finding was validated in an external cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001). CONCLUSIONS: The immunohistochemical finding of nuclear GR staining identified ACCs with high diagnostic accuracy. We propose that GR immunohistochemistry may complement the Weiss score in the diagnosis of ACC in cases that display borderline histology. The possibility that GR is transcriptionally active in these tumors, and may therefore be a therapeutic target, requires further study.
|
|
| 3. |
- Chou, M-Y, et al.
(författare)
-
Oxidation-specific epitopes are important targets of innate immunity.
- 2008
-
Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 263:5, s. 479-88
-
Forskningsöversikt (refereegranskat)abstract
- During the oxidation of LDL, a central pathophysiological component of atherogenesis, a wide variety of chemical and physical changes occur leading to the generation of oxidation-specific neoepitopes. These epitopes are not only immunogenic, leading to adaptive humoral responses, but are also a prominent target of multiple arcs of innate immunity. The pattern recognition receptors (PRRs) of innate immunity are germ line encoded, conserved by natural selection, and bind to pathogen-associated molecular patterns (PAMPs) common on multiple structures. However, it is not intuitive as to why they should recognize oxidation-specific neoepitopes. Yet it is clear that multiple macrophage scavenger receptors, which are classic PRRs, recognize oxidation-specific epitopes, such as those found on oxidized LDL (OxLDL). Other innate proteins, such as C-reactive protein, also bind to OxLDL. Natural antibodies (NAbs), the humoral arc of innate immunity, provide a nonredundant role in the first line of defence against pathogens, but are also believed to provide important homeostatic house-keeping functions against self-antigens. Our work demonstrates that oxidation-specific epitopes, as found on OxLDL, are a major target of NAbs. In this review, we will discuss the specific example of the prototypic NAb T15/E06, which is increased in atherosclerotic mice and mediates atheroprotection, and discuss the potential role of NAbs in atherogenesis, and in inflammation in general. We also review data that oxidation-specific epitopes are generated whenever cells undergo programmed cell death, forming a common set of PAMPs recognized by oxidation-specific PRRs on macrophages, NAbs and innate proteins. We present the hypothesis that oxidation-specific epitopes on apoptotic cells exerted evolutionary pressure for the conservation of these PRRs and also serve to maintain the expansion of a substantial proportion of NAbs directed to these stress-induced self-antigens.
|
|
| 4. |
|
|
| 5. |
- Learmonth, T., et al.
(författare)
-
Observation of multiple Zhang-Rice excitations in a correlated solid : Resonant inelastic X-ray scattering study of Li2CuO2
- 2007
-
Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 79:4, s. 47012-
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple Zhang-Rice type spectral features have been observed in resonant inelastic X-ray scattering (RIXS) from the quasi -one-dimensional cuprate charge transfer insulator Li2CuO2. The first feature appears at constant emission energy, and is associated with a Zhang-Rice singlet final state. The second is an interplaquette charge transfer excitation that results in a novel triplet Zhang-Rice -type final state. It is accompanied by the presence of a O 2p nonbonding to upper Hubbard band excitation at an energy close to that of a calculated triplet charge transfer Zhang-Rice -type excitation. The site selectivity and polarization rules associated with RIXS allows these two excitations to be distinguished.
|
|
| 6. |
- Bravo, J. M., et al.
(författare)
-
Incorporating Forecasts of Rainfall in Two Hydrologic Models Used for Medium-Range Streamflow Forecasting
- 2009
-
Ingår i: Journal of Hydrologic Engineering. - 1084-0699. ; 14:5, s. 435-445
-
Tidskriftsartikel (refereegranskat)abstract
- This study reports on the performance of two medium-range streamflow forecast models: (1) a multilayer feed-forward artificial neural network; and (2) a distributed hydrologic model. Quantitative precipitation forecasts were used as input to both models. The Furnas Reservoir on the Rio Grande River was selected as a case study, primarily because of the availability of quantitative precipitation forecasts from the Brazilian Center for Weather Prediction and Climate Studies and due to its importance in the Brazilian hydropower generating system. Streamflow forecasts were calculated for a drainage area of about 51,900 km(2), with lead times up to 12 days, at daily intervals. The Nash-Sutcliffe efficiency index, the root-mean-square error, the mean absolute error, and the mean relative error were used to assess the relative performance of the models. Results showed that the performance of streamflow forecasts was strongly dependent on the quality of quantitative precipitation forecasts used. The artificial neural network (ANN) method seemed to be less sensitive to precipitation forecast error relative to the distributed hydrological model. Hence, the latter presented a better skill in flow forecasting when using the more accurate perfect precipitation forecast. The conceptual hydrological model also demonstrates better forecast skill than ANN models for longer lead times, when the representation of the rainfall-runoff process and of the water storage in the watershed becomes more important than the flow routing along the drainage network. In addition, results obtained by incorporating a quantitative precipitation forecast in both models performed better than the current streamflow obtained by the Brazilian national electric system operator using statistical models which do not utilize information on precipitation, whether observed or forecast.
|
|
| 7. |
- Chou, J., et al.
(författare)
-
Nigrostriatal alterations in bone morphogenetic protein receptor II dominant negative mice
- 2008
-
Ingår i: Reconstructive Neurosurgery. - Wien : Springer. - 9783211782040 - 9783211782057 ; , s. 93-98
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: We previously demonstrated that exogenous application of bone morphogenetic protein 7 (BMP7) reduced 6-hydroxydopamine-mediated neurodegeneration in a rodent model of Parkinson's disease. The purpose of this study is to examine the endogenous neurotrophic properties of BMP Receptor II in dopaminergic neurons of the nigrostriatal pathway. METHODS: Adult male BMPRII dominant negative (BMPRIIDN) mice and their wild type controls (WT) were placed in the activity chambers for 3 days to monitor locomotor activity. Animals were sacrificed for tyrosine hydroxylase (TH) immunostaining. A subgroup of BMPRIIDN and WT mice were injected with high doses of methamphetamine (MA) and were sacrificed for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) histochemistry at 4 days after injection. RESULTS: BMPRIIDN mice had lower locomotor activity than the WT. There is a significant decrease in TH neuronal number in substantia nigra compacta, TH fiber density in the substantia nigra reticulata, and TH immunoreactivity in striatum in the BMPRIIDN mice, suggesting that deficiency in endogenous BMP signaling reduces dopaminergic innervation and motor function in the nigrostriatal pathway. Administration of MA increased TUNEL labeling in the substantia nigra in the BMPRIIDN mice. CONCLUSIONS: Endogenous BMPs have trophic effects on nigrostriatal dopaminergic neurons. Deficiency in BMP signaling increases vulnerability to insults induced by high doses of MA.
|
|
| 8. |
- Chou, Meng-Yun, et al.
(författare)
-
Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans.
- 2009
-
Ingår i: The Journal of clinical investigation. - 1558-8238. ; 119:5, s. 1335-49
-
Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.
|
|
| 9. |
- Mansy, Sheref S, et al.
(författare)
-
Structure and evolutionary analysis of a non-biological ATP-binding protein.
- 2007
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 371:2, s. 501-13
-
Tidskriftsartikel (refereegranskat)abstract
- We present a structural and functional analysis of the evolutionary optimization of a non-biological protein derived from a library of random amino acid sequences. A series of previously described in vitro selection experiments transformed a low-affinity ancestral sequence into a stably folded, high affinity ATP binding protein structure. While the evolutionarily optimized protein differs from its ancestral sequence through the accumulation of 12 amino acid mutations, the means by which those mutations enhance the stability and functionality of the protein were not well understood. We used a combination of mutagenesis, biochemistry, and NMR spectroscopy to investigate the structural and functional significance of each mutation. We solved the three-dimensional structure of the folding optimized protein by solution NMR, which revealed a fourth strand of the beta-sheet of the alpha/beta-fold that was not observed in an earlier crystallographic analysis of a less stable version of the protein. The structural rigidity of the newly identified beta-strand was confirmed by T1, T2, and heteronuclear nuclear Overhauser enhancement (NOE) measurements. Biochemical experiments were used to examine point mutations that revert the optimized protein back to the ancestral residue at each of the 12 sites. A combination of structural and functional data was then used to interpret the significance of each amino acid mutation. The enhanced ATP affinity was largely due to the emergence of a patch of positive charge density on the protein surface, while the increased solubility resulted from several mutations that increased the hydrophilicity of the protein surface, thereby decreasing protein aggregation. One mutation may stabilize the hydrophobic face of the beta-sheet.
|
|
| 10. |
|
|
