bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐Based Design of Benzoxazoles as new Inhibitors for D‐Alanyl – D‐Alanine Ligase
Authors: Tytgat Isabelle , Vandevuer Stéphane , Ortmans Isabelle , Sirockin Finton , Colacino Evelina , Van Bambeke Françoise , Duez Colette , Poupaert Jacques H. , Tulkens Paul M. , Dejaegere Annick , Prévost Martine 
Published: November 2009

AbstractD‐Alanyl – D‐alanine ligase is an enzyme which catalyzes the dimerization of D‐alanine, and, as such, has an essential role in bacterial cell wall biosynthesis. It has been shown that inhibition of D‐alanyl – D‐alanine ligase prevents bacterial growth. D‐Alanyl – D‐alanine ligase represents therefore a viable antimicrobial target. The 3D structure of this enzyme complexed with a phosphinophosphate inhibitor has been reported, which allows for structure‐based design studies. Four softwares (LUDI, MCSS, Autodock, and Glide) developed either for fragment or full‐molecule docking were compared and scored for their ability to position in the active site four prototypic ligands: two inhibitors, i.e. a phosphinophosphate derivative and D‐cycloserine, D‐alanine and D‐alanyl – D‐alanine. Best performances were obtained with Glide and MCSS. A short series of novel derivatives based on a 2‐phenylbenzoxazole scaffold was designed de novo on the basis of computational data. The best compound was found to fully inhibit the D‐alanyl – D‐alanine ligase of E. faecalis with an IC50 of 400 μM.
D∞h B2(BS)2−/2− and Td B(BS)4−: Boron sulfide clusters containing BB multiple bonds and B− tetrahedral centers
Authors: Yao Wen‐Zhi , Guo Jin‐Chang , Lu Hai‐Gang , Li Si‐Dian 
Published: November 2009

AbstractA density functional theory investigation on the geometrical and electronic properties of B4S (B2(BS)) and B5S (B(BS)) clusters has been performed in this work. Both the doublet B2(BS) ([SBBBBS]−) (D∞h, 2Πu) and the singlet B2(BS) ([SBBBBS]2−) (D∞h, 1Σ) proved to have perfect linear ground‐state structures containing a multiply bonded BB core (BB or BB) terminated with two BS groups, while Td B(BS) turned out to possess a perfect B− tetrahedral center directly corrected to four BS groups, similar to the corresponding boron hydride molecules of D∞h B2H, D∞h B2H, and Td BH, respectively. B4S2 and B5S4 neutrals, however, appeared to be much different: they favor a planar fan‐shaped C2v B4S2 (a di‐S‐bridged B4 rhombus) and a planar kite‐like C2v B5S4 (a di‐S‐bridged B3 triangle bonded to two BS groups), respectively. One‐electron detachment energies and symmetrical stretching vibrational frequencies are calculated for D∞h B2(BS) and Td B(BS) monoanions to facilitate their future characterizations. Neutral salts of B2(BS)2Li2 with an elusive BB triple bond and B(BS)4Li containing a tetrahedral B− center are predicted possible to be targeted in experiments. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
High‐lying core‐excited quartet states in Li‐like N4+ and F6+ ions
Authors: Zhuo Lin , Chen Feng , Gou Bing Cong 
Published: November 2009

AbstractThe variational method with mutilconfiguration interaction wave function is used to obtain the energies, fine structures, and hyperfine structures of high‐lying core‐excited quartet states 1s2lnl' 4Po(m) (m = 1–5) and 1s2pnp 4P(m) (m = 1–5) in Li‐like N4+ and F6+ ions, including the mass polarization and relativistic corrections. Restricted variational method is carried out to extrapolate a better energy. The oscillator strengths, lifetime, wavelengths, fine structure, and hyperfine structure for this system are also investigated to compare with other theoretical and experimental data in the literature. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
A correlated random‐effects model for normal longitudinal data with nonignorable missingness
Authors: Lin Huazhen , Liu Danping , Zhou Xiao‐Hua 
Published: November 2009

AbstractThe missing data problem is common in longitudinal or hierarchical structure studies. In this paper, we propose a correlated random‐effects model to fit normal longitudinal or cluster data when the missingness mechanism is nonignorable. Computational challenges arise in the model fitting due to intractable numerical integrations. We obtain the estimates of the parameters based on an accurate approximation of the log likelihood, which has higher‐order accuracy but with less computational burden than the existing approximation. We apply the proposed method it to a real data set arising from an autism study. Copyright © 2009 John Wiley & Sons, Ltd.
Adherence to antiretroviral therapy, virological response, and time to resistance in the Dakar cohort
Authors: Tournoud M. , Etard J. F. , Ecochard R. , DeGruttola V. 
Published: November 2009

AbstractIn 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time‐dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval‐censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy. Copyright © 2009 John Wiley & Sons, Ltd.
A conditional maximized sequential probability ratio test for Pharmacovigilance
Authors: Li Lingling , Kulldorff Martin 
Published: November 2009

AbstractThe importance of post‐marketing surveillance for drug and vaccine safety is well recognized as rare but serious adverse events may not be detected in pre‐approval clinical trials. In such surveillance, a sequential test is preferable, in order to detect potential problems as soon as possible. Various sequential probability ratio tests (SPRT) have been applied in near real‐time vaccine and drug safety surveillance, including Wald's classical SPRT with a single alternative and the Poisson‐based maximized SPRT (MaxSPRT) with a composite alternative. These methods require that the expected number of events under the null hypothesis is known as a function of timet. In practice, the expected counts are usually estimated from historical data. When a large sample size from the historical data is lacking, the SPRTs are biased due to the variance in the estimate of the expected number of events. We present a conditional maximized sequential probability ratio test (CMaxSPRT), which adjusts for the uncertainty in the expected counts. Our test incorporates the randomness and variability from both the historical data and the surveillance population. Evaluations of the statistical power for CMaxSPRT are presented under different scenarios. Copyright © 2009 John Wiley & Sons, Ltd.
Logistic quantile regression for bounded outcomes
Authors: Bottai Matteo , Cai Bo , McKeown Robert E. 
Published: November 2009

AbstractWhen research interest lies in continuous outcome variables that take on values within a known range (e.g. a visual analog scale for pain within 0 and 100 mm), the traditional statistical methods, such as least‐squares regression, mixed‐effects models, and even classic nonparametric methods such as the Wilcoxon's test, may prove inadequate. Frequency distributions of bounded outcomes are often unimodal, U‐shaped, and J‐shaped. To the best of our knowledge, in the biomedical and epidemiological literature bounded outcomes have seldom been analyzed by appropriate methods that, for one, correctly constrain inference to lie within the feasible range of values. In many respects, continuous bounded outcomes can be likened to probabilities or propensities. Yet, what has long been heeded when modeling the probability of binary outcomes with the widespread use of logistic and probit regression, so far appears to have been overlooked with continuous bounded outcomes with consequences at times disastrous. Logistic quantile regression constitutes an effective method to fill this gap. Copyright © 2009 John Wiley & Sons, Ltd.
Estimation of intervention effects using first or multiple episodes in clinical trials: The Andersen‐Gill model re‐examined
Authors: Cheung Yin Bun , Xu Ying , Tan Sze Huey , Cutts Felicity , Milligan Paul 
Published: November 2009

AbstractRandomized trials of interventions against infectious diseases are often analyzed using data on first or only episodes of disease, even when subsequent episodes have been recorded. It is often said that the Andersen‐Gill (AG) model gives a biased estimate of intervention effect if there is event dependency over time. We demonstrate that, in the presence of event dependency, an effective intervention may have an indirect effect on disease risk at time tj via its direct effect on disease risk at time ti, i<j, and that the AG model estimates the total effect instead of the direct effect alone. From a clinical and public health perspective, estimation of the total effect is important. Previous simulation studies showed contradictory results about the performance of the AG model in the presence of unobserved heterogeneity across individuals. We show that some of the previous studies unintentionally created informative censoring in their data generating process by including only a certain maximum number of events per individual. We re‐ran some previous simulations with and without altering this maximum. With reference to the situations often seen in pneumococcal vaccine trials, we evaluated the performance of the Cox model for time to first episode and the AG model for multiple episodes. We applied these models to re‐analyze data from a pneumococcal conjugate vaccine trial. We maintain that a careful clarification of research purpose is needed before one can choose a statistical model, and that the AG model is useful in the estimation of the total effect of an intervention. Copyright © 2009 John Wiley & Sons, Ltd.
False discovery rate and permutation test: An evaluation in ERP data analysis
Authors: Lage‐Castellanos, Agustín , Martínez‐Montes Eduardo , Hernández‐Cabrera Juan A. , Galán Lídice 
Published: November 2009

AbstractCurrent analysis of event‐related potentials (ERP) data is usually based on thea prioriselection of channels and time windows of interest for studying the differences between experimental conditions in the spatio‐temporal domain. In this work we put forward a new strategy designed for situations when there is nota prioriinformation about ‘when’ and ‘where’ these differences appear in the spatio‐temporal domain, simultaneously testing numerous hypotheses, which increase the risk of false positives. This issue is known as the problem of multiple comparisons and has been managed with methods that control the false discovery rate (FDR), such as permutation test and FDR methods. Although the former has been previously applied, to our knowledge, the FDR methods have not been introduced in the ERP data analysis. Here we compare the performance (on simulated and real data) of permutation test and two FDR methods (Benjamini and Hochberg (BH) and local‐fdr, by Efron). All these methods have been shown to be valid for dealing with the problem of multiple comparisons in the ERP analysis, avoiding thead hocselection of channels and/or time windows. FDR methods are a good alternative to the common and computationally more expensive permutation test. The BH method for independent tests gave the best overall performance regarding the balance between type I and type II errors. The local‐fdr method is preferable for high dimensional (multichannel) problems where most of the tests conform to the empirical null hypothesis. Differences among the methods according to assumptions, null distributions and dimensionality of the problem are also discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Optimal group‐sequential designs for simultaneous testing of superiority and non‐inferiority
Authors: Öhrn Fredrik , Jennison Christopher 
Published: November 2009

AbstractConfirmatory clinical trials comparing the efficacy of a new treatment with an active control typically aim at demonstrating either superiority or non‐inferiority. In the latter case, the objective is to show that the experimental treatment is not worse than the active control by more than a pre‐specified non‐inferiority margin. We consider two classes of group‐sequential designs that combine the superiority and non‐inferiority objectives: non‐adaptive designs with fixed group sizes and adaptive designs where future group sizes may be based on the observed treatment effect. For both classes, we derive group‐sequential designs meeting error probability constraints that have the lowest possible expected sample size averaged over a set of values of the treatment effect. These optimized designs provide an efficient means of reducing expected sample size under a range of treatment effects, even when the separate objectives of proving superiority and non‐inferiority would require quite different fixed sample sizes. We also present error spending versions of group‐sequential designs that are easily implementable and can handle unpredictable group sizes or information levels. We find the adaptive choice of group sizes to yield some modest efficiency gains; alternatively, expected sample size may be reduced by adding another interim analysis to a non‐adaptive group‐sequential design. Copyright © 2010 John Wiley & Sons, Ltd.
High Carbonyl Content Oxidized Starch Prepared by Hydrogen Peroxide and Its Thermoplastic Application
Authors: Zhang Shui‐Dong , Zhang Yu‐Rong , Wang Xiu‐Li , Wang Yu‐Zhong 
Published: November 2009

AbstractHydrogen peroxide was used to oxidize gelatinized starch to oxidized starch (OS) with degree of oxidation (DO) ranging from 0.096 to 0.554 depending on the H2O2/starch molar ratios used. Then glycerol was added to OS to produce thermoplastic oxidized starches (TPOS). Titrimetric determination of carboxyl and carbonyl groups, FT‐IR, 1H‐NMR and 13C‐NMR confirmed that at H2O2/starch molar ratios < 0.7, oxidized starch contained much more aldehyde than carboxyl groups, while at molar ratios up to 2.0, peroxide oxidation produced mainly carboxyl groups. Scanning electron microscopy (SEM) revealed that the oxidized starch particles (at DO 0.385) obtained a porous structure. The effect of DO on the structure and properties of OS, as well as mechanical properties and moisture resistance of TPOS was studied, respectively. With an increase in DO, the crystallinity, intrinsic viscosity and thermal stability of OS decreased markedly, the ability of OS to take up water decreased at low DO and increased at higher DO. These observations show that hydrogen peroxide can be used to oxidize starch in a controlled way. TPOS with DO 0.385 showed the best mechanical properties, its tensile strength was 6.1 MPa after placing in 100% relative humidity for 15 days.
The effect of axial beam force on moment–rotation curve of top and seat angels connections
Authors: Pirmoz Akbar , Danesh Fakhrodin , Farajkhah Vahid 
Published: November 2009

AbstractBolted top and seat angle connections are mainly designed to sustain gravitational loads of simply supported steel beams. However, the inherent flexural resistance of such connections may not be ignored when an accurate analysis of semirigid steel frames is desired. Current research aims at studying moment–rotation behaviour of this type under combined moment and axial tension force. Several refined three‐dimensional finite element models are created based on the previous experimental studies, and their accuracy is examined trough a comparison to test results from previous experimental studies. This study showed that the axial tension force reduces the connection initial stiffness and moment capacity. Based on the results obtained from analysing a series of finite element models under combined axial tension and moment loading, an equation is presented to estimate the affected moment–rotation response of such connections in terms of the connection geometrical properties, its moment–rotation response in the case of zero axial force and an expected axial tension force. Copyright © 2009 John Wiley & Sons, Ltd.
Seismic performance evaluation of tall and nonseismic‐designed wall‐type structures by shaking table tests
Authors: Park Tae‐Won , Chung Lan , Kim Jinkoo 
Published: November 2009

AbstractTwo 1/5‐scaled models of a nonseismic‐designed wall‐type structures were constructed and tested on a shaking table to evaluate their seismic performances. The prototype structure had shear walls only along the short side of the structure, which was a typical structural plan of apartment buildings constructed by tunnel forms before the seismic design code was enforced in Korea in 1989. Of the two models, one model was reinforced by steel angle sections placed on the walls and under the slabs for seismic retrofit. They were tested on a shaking table to investigate performance for earthquake ground excitations with various intensities. The experimental results showed that the nonseismic‐designed wall‐type structure without seismic retrofit failed to satisfy the life‐safety and collapse‐prevention performance objectives, whereas the retrofitted structure satisfied all the performance objectives. Copyright © 2009 John Wiley & Sons, Ltd.
Mean interference effects between two buildings: effects of close proximity
Authors: Amin J. A. , Ahuja A. K. 
Published: November 2009

AbstractThis paper presents the mean interference effects between a pair of buildings located in close proximity in a geometrical configuration of L‐ and T‐plan shapes. Experiments are carried out in a closed‐circuit wind tunnel on models of a 1:300 scale to measure the mean pressure distributions on two building models located in close proximity and on models in isolated position over an extended range of wind directions. The mean responses of buildings, namely block 1 and block 2 of L‐ and T‐shaped arrangements subjected to interference effects, are evaluated using the experimentally obtained wind loads and compared it with the responses of a similar building in isolation. Significant changes are observed in the responses of block 1 and block 2 of L‐ and T‐shaped arrangements as compared to a similar building in an isolated position. The interference levels are found to be dependent strongly on the angle of attack and the arrangement of the buildings with respect to each other. At wind incidence angle 0°, the presence of block 1 reduces the mean along the wind displacement of block 2 of the L‐ and T‐shaped arrangements up to 21% and 37%, respectively, as compared to a similar block in an isolated position. Copyright © 2009 John Wiley & Sons, Ltd.
A call for a new geoscience education research agenda
Authors: Lewis Elizabeth B. , Baker Dale R. 
Published: November 2009

AbstractA lack of qualified teachers and low enrollment in the geosciences exist at both secondary and tertiary levels in the United States. Consequently, it is unlikely that students will be able to achieve scientific literacy without an increase in both of these populations. To address these problems, we pose research questions, highlight sociocultural theories, and provide examples of other science education research as possible avenues by which to explore these related problems. We argue that such research studies are necessary to inform science education policy and advance national scientific literacy. © 2009 Wiley Periodicals, Inc. J Res Sci Teach 47:121–129, 2010
Major hepatectomy for perihilar cholangiocarcinoma
Authors: Unno Michiaki , Katayose Yu , Rikiyama Toshiki , Yoshida Hiroshi , Yamamoto Kuniharu , Morikawa Takanori , Hayashi Hiroki , Motoi Fuyuhiko , Egawa Shinichi 
Published: November 2009

AbstractBackground/purposeHilar cholangiocarcinoma and intrahepatic cholangiocarcinoma involving the hepatic hilus are defined as “perihilar cholangiocarcinoma”. The principle of surgical treatment is hemi‐hepatectomy or trisectionectomy of the liver, caudate lobectomy, and resection of the extrahepatic bile duct for complete resection of the tumor. The aim of this study was to review the outcomes of major hepatectomy for perihilar cholangiocarcinoma.MethodsUsing the Kaplan–Meier method and the Cox proportional hazards model, we analyzed the results in 125 patients with perihilar cholangiocarcinoma who had undergone major hepatectomy.ResultsRight hepatectomy, right trisectionectomy, left hepatectomy, and left trisectionectomy were performed in 66, 8, 49, and 2 patients, respectively. Curative resection was achieved in 79 patients (63.2%). Mortality and morbidity rates were 8.0 and 48.7%, respectively. The overall 1‐, 3‐, and 5‐year survival rates of all patients were 73.2, 36.7, and 34.7%, respectively. The median survival was 26.8 months. Multivariate analysis showed that the independent prognostic factors for overall survival were gender, histopathological grading, curative resection, and American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) pT.ConclusionsMajor hepatectomy for perihilar cholangiocarcinoma was acceptable and showed satisfactory outcomes. For long‐term survival in these patients, the surgeon should aim for complete resection of the tumor with negative margins.
Medical treatments: in association or alone, their role and their future perspectives
Authors: Tanaka Shinji , Arii Shigeki 
Published: November 2009

AbstractAccumulated understanding of the molecular networks in the state of oncogene addiction, i.e., the “Achilles’ heel of cancer,” has led to the development of novel targeted therapies. Using genome‐wide gene expression and network analysis, we have identified “Aurora kinase B” as a unique molecule to predict the lethal recurrence of hepatocellular carcinoma (HCC) even after curative hepatectomy. Comparative genomic hybridization (CGH)‐array analysis revealed the genomic instability was closely related to Aurora kinase B expression in HCC. Then, we analyzed the in vitro and in vivo effects of a selective inhibitor of Aurora kinase B on human HCC cells. Treatment with Aurora B inhibitor in vitro resulted in polyploidy and apoptotic cell death. The growth of orthotopic liver tumors was significantly suppressed by the Aurora B inhibitor. Our preclinical studies indicate that Aurora kinase B is a promising molecular target “Achilles’ heel” for the treatment of aggressive HCC.
Mesoporous Silica‐Supported Diarylammonium Catalysts for Esterification of Free Fatty Acids in Greases
Authors: Ngo Helen L. , Zafiropoulos Nicholas A. , Foglia Thomas A. , Samulski Edward T. , Lin Wenbin 
Published: November 2009

AbstractBiodiesel (BD), typically consisting of fatty acid methyl esters (FAME), has received much attention because it is a renewable biofuel that contributes little to global warming compared to petroleum‐based diesel fuel. The most common method used for BD production is based on the alkali‐catalyzed transesterification of first‐use refined oils and fats with an alcohol (e.g. methanol). These technologies, however, require significant modification when applied to second use materials such as greases because of their higher free fatty acid (FFA) content. Recently, we reported a series of insoluble porous polymer grafted diphenylammonium salts that efficiently esterified the FFA in greases to FAME. In this work, the diphenylammonium salts were supported onto two robust mesoporous silicas. The resulting catalysts had high esterification activity with >99% of the FFA in greases converted to FAME, and the FFA content in the treated greases was reduced to <1 wt%. The mesoporous silica‐supported catalysts displayed minimal transesterification activity.