Generalized Quasi-Likelihood Ratio Tests for Semiparametric Analysis of Covariance Models in Longitudinal Data

<p>We model generalized longitudinal data from multiple treatment groups by a class of semiparametric analysis of covariance models, which take into account the parametric effects of time dependent covariates and the nonparametric time effects. In these models, the treatment effects are represented by nonparametric functions of time and we propose a generalized quasi-likelihood ratio test procedure to test if these functions are identical. Our estimation procedure is based on profile estimating equations combined with local linear smoothers. We find that the much celebrated Wilks phenomenon which is well established for independent data still holds for longitudinal data if a working independence correlation structure is assumed in the test statistic. However, this property does not hold in general, especially when the working variance function is misspecified. Our empirical study also shows that incorporating correlation into the test statistic does not necessarily improve the power of the test. The proposed methods are illustrated with simulation studies and a real application from opioid dependence treatments. Supplementary materials for this article are available online.</p

Additional file 1 of Freeprotmap: waiting-free prediction method for protein distance map

Additional file 1: Supplementary No. 1

Ketocoumarin-Based Photoinitiators for High-Sensitivity Two-Photon Lithography

Ketocoumarins are attractive and distinct photosensitizers due to their high molar extinction coefficients, high intersystem crossing coefficients, and high photochemical stability. As a classic commercial ketocoumarin-based two-photon initiator, 7-diethylamino-3-thenoylcoumarin (DETC) was widely used in two-photon lithography. However, the large fluorescence quantum yield and low two-photon absorption cross section value greatly limit its application in high-throughput nanofabrication. In this work, a series of DETC derivatives were developed by extending the length of the alkyl chain and integrating different donor and acceptor groups. These ketocoumarin-based initiators, namely, compounds 1–7, were designed, synthesized, and unambiguously characterized. Compared with DETC, these compounds exhibit higher molar extinction coefficient, lower fluorescence quantum yield, higher two-photon absorption cross section, and improved sensitivity in two-photon lithography. Among these molecules, compound 7 with expanded π-electron systems and structures with enhanced intramolecular charge transfer exhibits the best sensitivity in two-photon lithography. With compound 7-based photoresist, many kinds of complex three-dimensional patterns can be fabricated using two-photon lithography at a writing speed of up to 60 mm s–1. The high two-photon initiation sensitivity makes these compounds promising candidates for commercialization and provides a new design concept for the development of new initiators

Histomorphological changes in two groups.

<p>H&E staining (200×). Acute rejection experimental group showed more inflammation infiltration and tissue damages than control group. Graft in experimental group have more inflammatory cell infiltration, tubular epithelial cell swelling and renal tissue damages.</p

Comparison of specific molecules expressions in grafts.

<p>Renal graft fibrosis was significantly accelerated in acute rejection experimental group. (A) Immunohistochemistry staining (100×) showed that the fibrotic protein expression of α-SMA was significantly upregulated in experimental group. (B) Immunohistochemistry staining (200×) showed that the fibrotic protein expression of TGF-β1 in graft was significantly upregulated in experimental group. (C) Quantitative image analyses showed the protein expression of α-SMA was significantly upregulated in experimental group. (D) Quantitative image analyses showed the protein expression of TGF-β1 was significantly upregulated in experimental group. (E)The fibrotic gene TGF-β1 mRNA expression was significantly upregulated in experimental group. Data were expressed as mean±SEM (n = 4 to 5). *<i>P</i><0.05 versus control group. **<i>P</i><0.01 versus control group.</p

Comparison of collagen depositions in grafts.

<p>Renal graft fibrosis was significantly accelerated in experimental group. (A) Trichrome staining (100×). Graft in experimental group showed extensive fibrosis. (B) Quantitative image analyses showed collagen depositions in renal graft increased with time. (C) The fibrotic gene pro-collagen-mRNA expression was significantly increased in acute rejection experimental group. Data were expressed as mean ± SEM (n = 4 to 5). *<i>P</i><0.05 versus control group. **<i>P</i><0.01 versus control group.</p

Antimicrobial susceptibility of the 284 pneumococcal isolates to 10 common antimicrobial agents.

<p>^<b>1</b> PEN: penicillin, CXM: cefuroxime, CRO: ceftriaxone, ERY: erythromycin, AZM: azithromycin, CLI: clindamycin, LEV: levofloxacin, MXF: moxifloxacin, VAN: vancomycin, SXT: trimethoprim-sulfamethoxazole</p><p>Antimicrobial susceptibility of the 284 pneumococcal isolates to 10 common antimicrobial agents.</p

Antimicrobial resistance pattern of 284 pneumococcal isolates.

<p>¹ PEN: penicillin, CXM: cefuroxime, CRO: ceftriaxone, ERY: erythromycin, AZM: azithromycin, CLI: clindamycin, LEV: levofloxacin, SXT: trimethoprim-sulfamethoxazole</p><p>Antimicrobial resistance pattern of 284 pneumococcal isolates.</p

Sequence types of 267 pneumococcal isolates among different serotypes.

<p>Sequence types of 267 pneumococcal isolates among different serotypes.</p

Comparison of changes in adenosine levels in two groups.

<p>Adenosine level was significantly upregulated in experimental group in which acute rejection existed. Adenosine levels in the kidney tissues were measured by HPLC. Data were described as mean ± SEM (n = 4 to 5). **<i>P</i><0.01 versus control group.</p