4,101 research outputs found
Non-perturbative improvement of operators with Wilson fermions
We outline two methods of constructing improved composite operators using Wilson fermions
Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model [v1; ref status: approved with reservations 1, http://f1000r.es/5l9]
Pleuropulmonary blastoma (PPB) is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF) in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of patients lack predisposing germline or mosaic mutations and have disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development
Religious Identity, Religious Attendance, and Parental Control
Using a national sample of adolescents aged 10–18 years and their parents (N = 5,117), this article examines whether parental religious identity and religious participation are associated with the ways in which parents control their children. We hypothesize that both religious orthodoxy and weekly religious attendance are related to heightened levels of three elements of parental control: monitoring activities, normative regulations, and network closure. Results indicate that an orthodox religious identity for Catholic and Protestant parents and higher levels of religious attendance for parents as a whole are associated with increases in monitoring activities and normative regulations of American adolescents
Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway
Neutrophil apoptosis and subsequent nonphlogistic clearance by surrounding phagocytes are key to the successful resolution of neutrophilic inflammation, with dysregulated apoptosis reported in multiple human inflammatory diseases. Enhancing neutrophil apoptosis has proresolution and anti-inflammatory effects in preclinical models of inflammation. Here we investigate the ability of the flavones apigenin, luteolin, and wogonin to induce neutrophil apoptosis in vitro and resolve neutrophilic inflammation in vivo. Human neutrophil apoptosis was assessed morphologically and by flow cytometry following incubation with apigenin, luteolin, and wogonin. All three flavones induced time- and concentration-dependent neutrophil apoptosis (apigenin, EC(50)=12.2 μM; luteolin, EC(50)=14.6 μM; and wogonin, EC(50)=28.9 μM). Induction of apoptosis was caspase dependent, as it was blocked by the broad-spectrum caspase inhibitor Q-VD-OPh and was associated with both caspase-3 and caspase-9 activation. Flavone-induced apoptosis was preceded by down-regulation of the prosurvival protein Mcl-1, with proteasomal inhibition preventing flavone-induced Mcl-1 down-regulation and apoptosis. The flavones abrogated the survival effects of mediators that prolong neutrophil life span, including lipoteichoic acid, peptidoglycan, dexamethasone, and granulocyte-macrophage colony stimulating factor, by driving apoptosis. Furthermore, wogonin enhanced resolution of established neutrophilic inflammation in a zebrafish model of sterile tissue injury. Wogonin-induced resolution was dependent on apoptosis in vivo as it was blocked by caspase inhibition. Our data show that the flavones induce neutrophil apoptosis and have potential as neutrophil apoptosis-inducing anti-inflammatory, proresolution agents.—Lucas, C. D., Allen, K. C., Dorward, D. A., Hoodless, L. J., Melrose, L. A., Marwick, J. A., Tucker, C. S., Haslett, C., Duffin, R., Rossi, A. G. Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway
Three-Dimensional Spectral Classification of Low-Metallicity Stars Using Artificial Neural Networks
We explore the application of artificial neural networks (ANNs) for the
estimation of atmospheric parameters (Teff, logg, and [Fe/H]) for Galactic F-
and G-type stars. The ANNs are fed with medium-resolution (~ 1-2 A) non
flux-calibrated spectroscopic observations. From a sample of 279 stars with
previous high-resolution determinations of metallicity, and a set of (external)
estimates of temperature and surface gravity, our ANNs are able to predict Teff
with an accuracy of ~ 135-150 K over the range 4250 <= Teff <= 6500 K, logg
with an accuracy of ~ 0.25-0.30 dex over the range 1.0 <= logg <= 5.0 dex, and
[Fe/H] with an accuracy ~ 0.15-0.20 dex over the range -4.0 <= [Fe/H] <= +0.3.
Such accuracies are competitive with the results obtained by fine analysis of
high-resolution spectra. It is noteworthy that the ANNs are able to obtain
these results without consideration of photometric information for these stars.
We have also explored the impact of the signal-to-noise ratio (S/N) on the
behavior of ANNs, and conclude that, when analyzed with ANNs trained on spectra
of commensurate S/N, it is possible to extract physical parameter estimates of
similar accuracy with stellar spectra having S/N as low as 13. Taken together,
these results indicate that the ANN approach should be of primary importance
for use in present and future large-scale spectroscopic surveys.Comment: 51 pages, 11 eps figures, uses aastex; to appear in Ap
Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions
Review: optical fiber sensors for civil engineering applications
Optical fiber sensor (OFS) technologies have developed rapidly over the last few decades, and various types of OFS have found practical applications in the field of civil engineering. In this paper, which is resulting from the work of the RILEM technical committee “Optical fiber sensors for civil engineering applications”, different kinds of sensing techniques, including change of light intensity, interferometry, fiber Bragg grating, adsorption measurement and distributed sensing, are briefly reviewed to introduce the basic sensing principles. Then, the applications of OFS in highway structures, building structures, geotechnical structures, pipelines as well as cables monitoring are described, with focus on sensor design, installation technique and sensor performance. It is believed that the State-of-the-Art review is helpful to engineers considering the use of OFS in their projects, and can facilitate the wider application of OFS technologies in construction industry
DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma
The pathogenesis of cystic nephroma of the kidney has interested pathologists for over 50 years. Emerging from its initial designation as a type of unilateral multilocular cyst, cystic nephroma has been considered as either a developmental abnormality or a neoplasm or both. Many have viewed cystic nephroma as the benign end of the pathologic spectrum with cystic partially differentiated nephroblastoma and Wilms tumor, whereas others have considered it a mixed epithelial and stromal tumor. We hypothesize that cystic nephroma, like the pleuropulmonary blastoma in the lung, represents a spectrum of abnormal renal organogenesis with risk for malignant transformation. Here we studied DICER1 mutations in a cohort of 20 cystic nephromas and 6 cystic partially differentiated nephroblastomas, selected independently of a familial association with pleuropulmonary blastoma and describe four cases of sarcoma arising in cystic nephroma, which have a similarity to the solid areas of type II or III pleuropulmonary blastoma. The genetic analyses presented here confirm that DICER1 mutations are the major genetic event in the development of cystic nephroma. Further, cystic nephroma and pleuropulmonary blastoma have similar DICER1 loss of function and ‘hotspot' missense mutation rates, which involve specific amino acids in the RNase IIIb domain. We propose an alternative pathway with the genetic pathogenesis of cystic nephroma and DICER1-renal sarcoma paralleling that of type I to type II/III malignant progression of pleuropulmonary blastoma
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