A goodness-of-fit test for parametric and semi-parametric models in multiresponse regression

We propose an empirical likelihood test that is able to test the goodness of fit of a class of parametric and semi-parametric multiresponse regression models. The class includes as special cases fully parametric models; semi-parametric models, like the multiindex and the partially linear models; and models with shape constraints. Another feature of the test is that it allows both the response variable and the covariate be multivariate, which means that multiple regression curves can be tested simultaneously. The test also allows the presence of infinite-dimensional nuisance functions in the model to be tested. It is shown that the empirical likelihood test statistic is asymptotically normally distributed under certain mild conditions and permits a wild bootstrap calibration. Despite the large size of the class of models to be considered, the empirical likelihood test enjoys good power properties against departures from a hypothesized model within the class.Comment: Published in at http://dx.doi.org/10.3150/09-BEJ208 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Estimation of Semiparametric Models when the Criterion Function is not Smooth

We provide easy to verify sufficient conditions for the consistency and asymptotic normality of a class of semiparametric optimization estimators where the criterion function does not obey standard smoothness conditions and simultaneously depends on some nonparametric estimators that can themselves depend on the parameters to be estimated. Our results extend existing theories like those of Pakes and Pollard (1989), Andrews (1994a) and Newey (1994). We also show that bootstrap provides asymptotically correct confidence regions for the finite dimensional parameters. We apply our results to two examples: a 'hit rate' and a partially linear median regression with some endogenous regressors.Empirical processes, non-smooth criterion, semiparametric estimation, stochastic equicontinuity.

Chromatin Laser Imaging Reveals Abnormal Nuclear Changes for Early Cancer Detection

We developed and applied rapid scanning laser-emission microscopy to detect abnormal changes in cell nuclei for early diagnosis of cancer and cancer precursors. Regulation of chromatins is essential for genetic development and normal cell functions, while abnormal nuclear changes may lead to many diseases, in particular, cancer. The capability to detect abnormal changes in apparently normal tissues at a stage earlier than tumor development is critical for cancer prevention. Here we report using LEM to analyze colonic tissues from mice at-risk for colon cancer by detecting prepolyp nuclear abnormality. By imaging the lasing emissions from chromatins, we discovered that, despite the absence of observable lesions, polyps, or tumors under stereoscope, high-fat mice exhibited significantly lower lasing thresholds than low-fat mice. The low lasing threshold is, in fact, very similar to that of adenomas and is caused by abnormal cell proliferation and chromatin deregulation that can potentially lead to cancer. Our findings suggest that conventional methods, such as colonoscopy, may be insufficient to reveal hidden or early tumors under development. We envision that this work will provide new insights into LEM for early tumor detection in clinical diagnosis and fundamental biological and biomedical research of chromatin changes at the biomolecular level of cancer development

Prostate Cancers Detected During 5α-Reductase Inhibitor Use Are Smaller, De-Differentiated, But Confined when Compared To Controls

Rationale: To compare cancers detected during use of 5α-reductase inhibitors (5αRI) with cancers detected in untreated controls stratified for tumor size

Routine Use of Unilateral and Bilateral Radial Arteries for Coronary Artery Bypass Graft Surgery

AbstractObjectives. This study sought to evaluate the routine use of radial artery (RA) grafts in patients undergoing coronary artery revascularization.Background. Previous long-term studies have documented poor patency of saphenous vein grafts compared with internal thoracic artery (ITA) grafts.Methods. We performed a prospective review of 175 of 249 consecutive patients.Results. Fifty-four patients had bilateral RAs harvested. Mean number (±SD) of grafts/patient was 3.27 ± 0.93, with 2.76 ± 0.97 arterial grafts; a mean of 1.53 ± 0.68 grafts were performed with the RA. The operative mortality rate was 1.6%. No deaths were related to RA grafts, and there were no RA harvest site hematomas or infections. Transient dysesthesia 1 day to 4 weeks in duration occurred in the distribution of the lateral antebrachial cutaneous nerve in six extremities (2.6%). Elective cardiac catheterization in 60 patients at 12 weeks postoperatively demonstrated a 95.7% patency rate.Conclusions. Because of potential benefit of long-term patency associated with arterial grafts, minimal morbidity and mortality associated with use of the RA and excellent short-term patency rates, we cautiously recommend use of one or both RAs as additional conduits to be used concomitantly with the ITA for arterial revascularization of the coronary arteries

Poly[ethano­lbis(μ3-2-thio­xo-1,2-dihydro­pyridin-1-olato)dilithium(I)]

The title compound, [Li2(C5H4NOS)2(C2H6O)]n, having two formula units in the asymmetric unit, forms infinite chains of Li2O2 rhombi along b, consisting of four independent Li and O atoms. Metal binding to 2-thio­oxo-1,2-dihydro­pyridin-1-olate occurs in a bidentate fashion via O and S, and in a monodentate manner via the N-oxide O atom. π–π Inter­actions between polymeric chains are evident from centroid-to-centroid distances of pyridine­thione fragments of 3.461 (6)–3.607 (6) Å. The N—O and C—S bond lengths are distinctively different from those in hitherto investigated NiII, ZnII and (H3C)2TlIII complexes of 2-thio­oxo-1,2-dihydro­pyridin-1-olate, but correlate with those reported for 1-hydr­oxy- and 1-alkoxy­pyridine-2(1H)-thio­nes in the solid state

MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure

[[abstract]]Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE) is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs) have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.[[notice]]補正完畢[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]電子

Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage

Cockayne syndrome (CS) is a human DNA repair-deficient disease that involves transcription coupled repair (TCR), in which three gene products, Cockayne syndrome A (CSA), Cockayne syndrome B (CSB), and ultraviolet stimulated scaffold protein A (UVSSA) cooperate in relieving RNA polymerase II arrest at damaged sites to permit repair of the template strand. Mutation of any of these three genes results in cells with increased sensitivity to UV light and defective TCR. Mutations in CSA or CSB are associated with severe neurological disease but mutations in UVSSA are for the most part only associated with increased photosensitivity. This difference raises questions about the relevance of TCR to neurological disease in CS. We find that CSB-mutated cells, but not UVSSA-deficient cells, have increased levels of intramitochondrial reactive oxygen species (ROS), especially when mitochondrial complex I is inhibited by rotenone. Increased ROS would result in oxidative damage to mitochondrial proteins, lipids, and DNA. CSB appears to behave as an electron scavenger in the mitochondria whose absence leads to increased oxidative stress. Mitochondrial ROS, however, did not cause detectable nuclear DNA damage even when base excision repair was blocked by an inhibitor of polyADP ribose polymerase. Neurodegeneration in Cockayne syndrome may therefore be associated with ROS-induced damage in the mitochondria, independent of nuclear TCR. An implication of our present results is that mitochondrial dysfunction involving ROS has a major impact on CS-B pathology, whereas nuclear TCR may have a minimal role

Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

[[abstract]]Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.[[notice]]補正完畢[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]電子