bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling multi‐way data with linearly dependent loadings
Authors: Bro Rasmus , Harshman Richard A. , Sidiropoulos Nicholas D. , Lundy Margaret E. 
Published: January 2009

AbstractA generalization/specialization of the PARAFAC model is developed that improves its properties when applied to multi‐way problems involving linearly dependent factors. This model is called PARALIND (PARAllel profiles with LINear Dependences). Linear dependences can arise when the empirical sources of variation being modeled by factors are causally or logically linked during data generation, or circumstantially linked during data collection. For example, this can occur in a chemical context when end products are related to the precursor or in a psychological context when a single stimulus generates two incompatible feelings at once. For such cases, the most theoretically appropriate PARAFAC model has loading vectors that are linearly dependent in at least one mode, and when collinear, are nonunique in the others. However, standard PARAFAC analysis of fallible data will have neither of these features. Instead, latent linear dependences become high surface correlations and any latent nonuniqueness is replaced by a meaningless surface‐level ‘unique orientation’ that optimally fits the particular random noise in that sample. To avoid these problems, any set of components that in theory should be rank deficient are re‐expressed in PARALIND as a product of two matrices, one that explicitly represents their dependency relationships and another, with fewer columns, that captures their patterns of variation. To demonstrate the approach, we apply it first to fluorescence spectroscopy (excitation‐emission matrices, EEM) data in which concentration values for two analytes covary exactly, and then to flow injection analysis (FIA) data in which subsets of columns are logically constrained to sum to a constant, but differently in each of two modes. In the PARAFAC solutions of the EEM data, all factors are ‘unique’ but this is only meaningful for two of the factors that are also unique at the latent level. In contrast, the PARALIND solutions directly display the extent and nature of partial nonuniqueness present at the latent level by exhibiting a corresponding partial uniqueness in their recovered loadings. For the FIA data, PARALIND constraints restore latent uniqueness to the concentration estimates. Comparison of the solutions shows that PARALIND more accurately recovers latent structure, presumably because it uses fewer parameters and hence fits less error. Copyright © 2009 John Wiley & Sons, Ltd.
Re‐parameterization of five‐parameter logistic function
Authors: Liao Jason J. Z. , Liu Rong 
Published: January 2009

AbstractRecently, the five‐parameter logistic (5PL) function has seen increased use as a model for bioassay dose‐response curves. The 5PL function takes curve asymmetry into consideration to overcome some drawbacks of the four‐parameter logistic (4PL) function. These drawbacks include biased estimates of important model parameters, poor characterization of pharmacological pathways and the mechanisms, and inaccurate inference of drug‐receptor interactions. However, currently used 5PL functional form does not have the same practical useful parameter interpretation as the 4PL function. In this paper, we re‐parameterize the 5PL function to preserve the practical useful parameter interpretation of the 4PL. Comparing to the currently used 5PL, the re‐parameterized 5PL function preserves practical useful parameter interpretation of 4PL and has better statistical properties in terms of bias and mean squared error (MSE). Copyright © 2009 John Wiley & Sons, Ltd.
Photoinduced Reactions of cis,trans,cis‐[PtIV(N3)2(OH)2(NH3)2] with 1‐Methylimidazole
Authors: Phillips Hazel I. A. , Ronconi Luca , Sadler Peter J. 
Published: January 2009

AbstractLighting up new platinum anticancer complexes: Photoactivation of a platinum(IV) diazido anticancer complex in the presence of a derivative of imidazole, an important constituent of biomolecules, gives surprising photoproducts, including a tetrakis imidazole platinum(II) adduct (see figure), together with free azide, dioxygen and ammonia.magnified imageThe photodecomposition of cis,trans,cis‐[PtIV(N3)2(OH)2(NH3)2] in phosphate buffered saline (PBS), as well as in the presence of 1‐methylimidazole (1‐MeIm), induced by UVA light (centred at λ=365 nm) has been studied by multinuclear NMR spectroscopy. We show that photoreduction, photoisomerisation and trans‐labilisation pathways are involved. The photodecomposition pathway in PBS, which involves azide release, as detected by 14N NMR spectroscopy, appears to differ from that in acidic aqueous conditions, under which N2 is a product. A number of trans‐{N‐PtII‐NH3} species were also observed as photoproducts, as well as the release of free ammonia with a corresponding increase in pH. Oxygen was also detected as a product in solution. In the presence of 1‐methylimidazole, surprisingly the major photoproduct was the tetra‐substituted PtII complex [PtII(1‐MeIm‐N3)4]2+ (structure confirmed by crystallography), even at a Pt/1‐MeIm molar ratio of 1:1, together with cis‐ and trans‐[PtII(NH3)2(1‐MeIm‐N3)2]2+ as minor products. In these photoinduced 1‐MeIm reactions, free ammonia, azide and oxygen were also detected. The results from this study illustrate that photoinduced reactions of platinum complexes can lead to novel reaction pathways, and therefore to new cytotoxic mechanisms in cancer cells.
Multi‐Drug‐Resistance‐Reverting Agents: 2‐Aryloxazole and 2‐Arylthiazole Derivatives as Potent BCRP or MRP1 Inhibitors
Authors: Colabufo Nicola A. , Berardi Francesco , Perrone Maria Grazia , Cantore Mariangela , Contino Marialessandra , Inglese Carmela , Niso Mauro , Perrone Roberto 
Published: January 2009

AbstractThe 2‐aryloxazole and 2‐arylthiazole scaffolds were used for generating compounds that we characterized for their inhibitory activity toward ATP binding cassette transporters involved in multi‐drug resistance, such as BCRP and MRP1, by using tumor cell lines overexpressing each transporter. These SAR studies are a significant step toward improving the inhibitory potency against P‐glycoprotein, BCRP, and MRP1.magnified image2‐Aryloxazole and 2‐arylthiazole derivatives were evaluated for their inhibitory activity toward P‐glycoprotein (P‐gp) as well as their selectivity toward other ABC transporters involved in multi‐drug resistance such as BCRP and MRP1. These derivatives have 6,7‐dimethoxytetrahydroisoquinoline or cyclohexylpiperazine moieties, which are the same basic nuclei of the potent P‐gp inhibitors MC70 (EC50=0.05 μM) and PB28 (EC50=0.55 μM), respectively. The results demonstrate that 2‐aryloxazole and 2‐arylthiazole derivatives, planned as cycloisosteres of MC70, were found to be less potent than the reference compound in inhibiting P‐gp. These compounds were evaluated for their BCRP and MRP1 inhibitory activities. In particular, 6,7‐dimethoxytetrahydroisoquinoline derivatives, unsubstituted, 3‐Br, 3‐Cl, and 3‐OCH3 2‐aryloxalzole derivatives showed the best BCRP inhibitory activity (EC50 range: 0.24–0.46 μM). In contrast, all cyclohexylpiperazine derivatives except one (EC50=0.56 μM), showed decreased BCRP inhibitory activity. All compounds tested were unable to inhibit the MRP1 pump, with the exception of the 2‐OCH3 and 4‐OCH3 derivatives of the 6,7‐dimethoxytetrahydroisoquinoline series, which displayed high MRP1 inhibitory activity (EC50=0.84 and 0.90 μM, respectively).
A phase 2, randomized study of SB‐485232, rhIL‐18, in patients with previously untreated metastatic melanoma
Authors: Tarhini Ahmad A. , Millward Michael , Mainwaring Paul , Kefford Richard , Logan Ted , Pavlick Anna , Kathman Steven J. , Laubscher Kevin H. , Dar Mohammed M. , Kirkwood John M. 
Published: January 2009

AbstractBACKGROUND:Phase 1 studies demonstrated evidence of recombinant human IL‐18 (rhIL‐18)‐mediated immunomodulatory and clinical activity, and defined a biologically active dose range.METHODS:A phase 2 study of rhIL‐18 was conducted in untreated AJCC stage IV melanoma. Patients were randomized to 1 of 3 dose groups (0.01, 0.1, and 1.0 mg/kg/d) of rhIL‐18 administered as 5 daily intravenous infusions repeated every 28 days. A 2‐stage design with a stopping rule was used.RESULTS:A total of 64 patients (median age, 57.5 years) with metastatic melanoma (M1a/b (30), M1c (34)) were accrued to stage I, and randomized to 3 groups (21 [0.01 mg/kg/d], 21 [0.1 mg/kg/d], 22 [1.0 mg/kg/d]). Five patients experienced 10 grade 3 drug‐related adverse events (AEs): polyarthritis (1 subject: 0.01 mg/kg); deep vein thrombosis, pulmonary embolism (1:0.01 mg/kg); cognitive disorder (1:0.1 mg/kg); fatigue, dyspnea, pleural effusion, lymphopenia (1:1.0 mg/kg); fatigue, lymphopenia (1:1.0 mg/kg). One patient experienced a grade 4 AE of increased lipase (0.1 mg/kg) that led to permanent discontinuation from the study. Among 63 subjects evaluable for response, 1 (M1c; 0.01 mg/kg) achieved a partial response after 4 cycles. Four subjects (3 at 0.01 mg/kg and 1 at 1.0 mg/kg) had stable disease maintained for 6 months or longer. Due to the low apparent level of clinical efficacy using RECIST criteria, the study was terminated at the end of stage 1. The median progression free survival for the 3 groups was 7.5 (0.01), 7.4 (0.1), and 7.3 (1.0) weeks.CONCLUSIONS:rIL‐18 as tested in this trial was well tolerated, but had limited activity as a single agent in patients with metastatic melanoma. Cancer 2009. © 2009 American Cancer Society.
High‐order three‐dimensional discontinuous deformation analysis (3‐D DDA)
Authors: Beyabanaki S. Amir Reza , Jafari Ahmad , Yeung M. Ronald 
Published: January 2009

AbstractThree‐dimensional discontinuous deformation analysis (3‐D DDA) with high‐order displacement functions has been derived for the requirement of highly accurate stress and strain calculations. The high‐order displacement function allows nonlinear distributions of stresses and strains within a discrete block, which significantly enhances 3‐D DDA as an analysis technique. Formulations of stiffness and force matrices in second‐ and third‐order 3‐D DDA due to elastic stress, initial stress, body force, point load, fixed point, inertial force, normal and shear contact forces and friction force are presented. The VC++ codes for the second‐ and third‐order cases have been developed, and they have been applied to examples of 3‐D beams, bending under various loading conditions applied at the end and to an example of discontinuous problem. Results of modeling, are well in agreement with theoretical solutions. In contrast, the results calculated for the same model, using original first‐order 3‐D DDA are far from the theoretical solutions. Copyright © 2009 John Wiley & Sons, Ltd.
[99mTc]polyamine analogs as potential tumor imaging agent
Authors: Wan Wei‐xing , Yang Min , Pan Shang‐ren , Yu Chun‐jing , Wu Na‐jing 
Published: January 2009

AbstractPolyamines are essential for the growth and survival of all cells with biosynthesis and transportation of polyamines being very active in tumors. With the aim of developing a new tumor imaging agent, three artificial synthetic polyamine analogs, diethylenetriamine (DETA), triethylenetetramine (TETA), and tetraethylenepentamine (TEPA), were labeled with 99mTc. The 99mTc‐labeled complexes were characterized by TLC and studied for stability. 99mTc‐DETA, 99mTc‐TETA, and 99mTc‐TEPA were formed in high yields and found to be stable. 99mTc‐DETA, 99mTc‐TETA, and 99mTc‐TEPA revealed high tumor uptakes of 0.65, 0.58, and 0.59% ID/g at 4 h pi, respectively, in HepA tumor‐bearing mice. The ratios of the tumor to the contralataral muscle (T/CM) were 13.68, 5.99, and 9.81, respectively. SPECT images revealed clear visualization of tumors. Excretion routes were mainly through urine and feces. The tumor‐to‐muscle count density ratios of 99mTc‐DETA, 99mTc‐TETA, and 99mTc‐TEPA were 2.47, 2.45, and 2.91, respectively. [99mTc]‐labeled polyamine analogs are promising agents for tumor imaging and warrant further evaluation. Drug Dev Res 69:520–525, 2008. © 2008 Wiley‐Liss, Inc.
Mapping the Mechanism of Nickel‐Ferrophite Catalysed Methylation of Baylis–Hillman‐Derived SN2′ Electrophiles
Authors: Novak Andrew , Calhorda Maria José , Costa Paulo Jorge , Woodward Simon 
Published: January 2009

AbstractEnantioselective Ni‐catalysed methylation of Baylis–Hillman‐derived allylic electrophiles in the presence of ferrophite ligands has been investigated computationally and experimentally. The sense and degree of enantioselectivity attained is independent of both the leaving group and the isomeric structure of the initial allylic halide. DFT studies support the selective formation of a limited number of energetically favoured anti and syn π‐allyl intermediates. The observed regio‐ and enantioselectivity can be rationalised based on the energetics of these structures. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Chiral N‐Phosphonylimine Chemistry: Asymmetric Synthesis of N‐Phosphonyl β‐Amino Weinreb Amides
Authors: Kaur Parminder , Nguyen Thao , Li Guigen 
Published: January 2009

AbstractVarious chiral N‐phosphonyl β‐amino Weinreb amides were synthesized by treating chiral N‐phosphonyl imines with the lithium enolate of N‐methoxy‐N‐methylacetamide. The N,N‐protection groups on chiral N‐phosphonyl imines and the types of deprotonation bases for enolate generation were found to be crucial for the successful synthesis. Eleven Weinreb amides were obtained in excellent chemical yields (92 to 98 %) and good to excellent diastereoselectivities (up to dr = 99:1). The absolute structures were unambiguously determined by converting the products into authentic samples and by comparing their optical rotation values.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A Magnetically Separable Heterogeneous Deallylation Catalyst: [CpRu(η3‐C3H5)(2‐pyridinecarboxylato)]PF6 Complex Supported on a Ferromagnetic Microsize Particle Fe3O4@SiO2
Authors: Hirakawa Takuya , Tanaka Shinji , Usuki Naoki , Kanzaki Hisao , Kishimoto Mikio , Kitamura Masato 
Published: January 2009

AbstractThe highly reactive and chemoselective homogeneousdeallylation catalyst CpRu(η3‐C3H5)(4‐substituted‐2‐pyridinecarboxylato) was immobilized on microsize spherical Fe3O4@SiO2 particles. The resultant heterogeneous catalyst displays high saturation magnetization, weak coercive forces and high levels of dispersibility. The catalyst has increased the utility of deallylation by allowing the reaction to be conducted without extra additives. The only co‐product of the reaction is a volatile allyl ether compound. Here, we demonstrate the efficient deallylation and separation of highly polar multifunctional compounds as well as multiple rounds of catalyst recycling without significant loss of reactivity. The usefulness of this catalyst has been confirmed by the synthesis of a triribonucleotide 3–5 U. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
An Asymmetric Approach towards (–)‐Aphanorphine and Its Analogues
Authors: Donets Pavel A. , Goeman Jan L. , Van der Eycken Johan , Robeyns Koen , Van Meervelt Luc , Van der Eycken Erik V. 
Published: January 2009

AbstractA short enantioselective approach towards the alkaloid(–)‐aphanorphine and its substituted analogues is described. The enantiomerically pure starting material for the synthesis was obtained by asymmetric hydrogenation in the presence of the Rh–(S)‐PipPhos complex. Microwave‐assisted Heckcyclization selectively provided the seven‐membered 3‐benzazepine ring. Further, the assembly of the tricyclic core of the alkaloid was accomplished by intramolecular radical cyclization. The X‐ray structure confirming the absolute configuration of the obtained products is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Dimensioning of secondary and tertiary control reserve by probabilistic methods
Authors: Maurer Christoph , Krahl Simon , Weber Holger 
Published: January 2009

AbstractGiven the rising share of intermittent generation out of renewable energy sources on the one hand and the increased regulatory efforts to lower transmission costs and tariffs on the other hand, the optimal dimensioning of necessary control reserve has gained additional importance during the last years. Grid codes like the UCTE Operation Handbook do not provide definitive and unambiguous methods for dimensioning of secondary and tertiary control reserves. This paper therefore presents a method which calculates the necessary control reserve considering all important drivers for power imbalances like power plant outages, load variations and forecast error. For dimensioning, a probabilistic criterion, the accepted probability of insufficient control reserve, is used. Probability density functions of control area imbalances are calculated using a convolution algorithm. This paper provides analyses for a stylised example system to demonstrate the capabilities of the method. In a sensitivity analysis the impact of drivers like plant failures and forecast errors of load and generation is shown. The presented method is used by transmission system operators and regulatory authorities to determine and substantiate the necessary amount of control reserve. Copyright © 2009 John Wiley & Sons, Ltd.
Unbiased estimation of odds ratios: combining genomewide association scans with replication studies
Authors: Bowden Jack , Dudbridge Frank 
Published: January 2009

AbstractOdds ratios or other effect sizes estimated from genome scans are upwardly biased, because only the top‐ranking associations are reported, and moreover only if they reach a defined level of significance. No unbiased estimate exists based on data selected in this fashion, but replication studies are routinely performed that allow unbiased estimation of the effect sizes. Estimation based on replication data alone is inefficient in the sense that the initial scan could, in principle, contribute information on the effect size. We propose an unbiased estimator combining information from both the initial scan and the replication study, which is more efficient than that based just on the replication. Specifically, we adjust the standard combined estimate to allow for selection by rank and significance in the initial scan. Our approach explicitly allows for multiple associations arising from a scan, and is robust to mis‐specification of a significance threshold. We require replication data to be available but argue that, in most applications, estimates of effect sizes are only useful when associations have been replicated. We illustrate our approach on some recently completed scans and explore its efficiency by simulation. Genet. Epidemiol. 33:406–418, 2009. © 2009 Wiley‐Liss, Inc.
Genetic background comparison using distance‐based regression, with applications in population stratification evaluation and adjustment
Authors: Li Qizhai , Wacholder Sholom , Hunter David J. , Hoover Robert N. , Chanock Stephen , Thomas Gilles , Yu Kai 
Published: January 2009

AbstractPopulation stratification (PS) can lead to an inflated rate of false‐positive findings in genome‐wide association studies (GWAS). The commonly used approach of adjustment for a fixed number of principal components (PCs) could have a deleterious impact on power when selected PCs are equally distributed in cases and controls, or the adjustment of certain covariates, such as self‐identified ethnicity or recruitment center, already included in the association analyses, correctly maps to major axes of genetic heterogeneity. We propose a computationally efficient procedure, PC‐Finder, to identify a minimal set of PCs while permitting an effective correction for PS. A general pseudo F statistic, derived from a non‐parametric multivariate regression model, can be used to assess whether PS exists or has been adequately corrected by a set of selected PCs. Empirical data from two GWAS conducted as part of the Cancer Genetic Markers of Susceptibility (CGEMS) project demonstrate the application of the procedure. Furthermore, simulation studies show the power advantage of the proposed procedure in GWAS over currently used PS correction strategies, particularly when the PCs with substantial genetic variation are distributed similarly in cases and controls and therefore do not induce PS. Genet. Epidemiol. 33:432–441, 2009. © 2009 Wiley‐Liss, Inc.
Quantifying and correcting for the winner's curse in genetic association studies
Authors: Xiao Rui , Boehnke Michael 
Published: January 2009

AbstractGenetic association studies are a powerful tool to detect genetic variants that predispose to human disease. Once an associated variant is identified, investigators are also interested in estimating the effect of the identified variant on disease risk. Estimates of the genetic effect based on new association findings tend to be upwardly biased due to a phenomenon known as the “winner's curse.” Overestimation of genetic effect size in initial studies may cause follow‐up studies to be underpowered and so to fail. In this paper, we quantify the impact of the winner's curse on the allele frequency difference and odds ratio estimators for one‐ and two‐stage case‐control association studies. We then propose an ascertainment‐corrected maximum likelihood method to reduce the bias of these estimators. We show that overestimation of the genetic effect by the uncorrected estimator decreases as the power of the association study increases and that the ascertainment‐corrected method reduces absolute bias and mean square error unless power to detect association is high. Genet. Epidemiol. 33:453–462, 2009. © 2009 Wiley‐Liss, Inc.
Neuropsychiatric symptoms in mild cognitive impairment: differences by subtype and progression to dementia
Authors: Edwards Emily R. , Spira Adam P. , Barnes Deborah E. , Yaffe Kristine 
Published: January 2009

AbstractBackgroundNeuropsychiatric symptoms (NPS) are common in patients with mild cognitive impairment (MCI). Little is known, however, about how NPS vary by MCI subtype (i.e. amnestic, single domain non‐memory, and multiple domain). In addition, it is unclear whether NPS increase risk of progression to dementia. We investigated the distribution of NPS across MCI subtypes and determined whether NPS increase risk of progression to dementia.MethodParticipants were 521 patients diagnosed with MCI at the Alzheimer's Research Centers of California between 1988 and 1999. At baseline, patients were classified into MCI subtypes and were assessed for NPS.ResultsThe mean number of NPS was 2.3 (range 0–9.6; 74% had ≥1 NPS). Patients with ≥4 NPS had more medical comorbidities and greater functional impairment (p ≤ 0.0001 for both). Patients with ≥4 NPS were more likely than patients with 0–3 NPS to have amnestic MCI (81% vs 71%, respectively, p = 0.03), and patients with amnestic MCI were more likely than those with other subtypes to exhibit depressive symptoms. Patients with ≥4 NPS had nearly 2.5 times the odds of developing dementia at follow‐up than patients with 0–3 NPS (adjusted OR = 2.44, 95% CI 1.07, 5.55).ConclusionNPS are common in MCI patients. Those with an elevated number of NPS may be more likely to have the amnestic subtype of MCI, and depression may be more common in amnestic MCI than in other subtypes. An elevated number of NPS may increase risk of progression to dementia for patients with MCI. Copyright © 2009 John Wiley & Sons, Ltd.