bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II Trial of Tremelimumab in Patients With Metastatic Melanoma
Authors: Camacho Luis H. , Antonia Scott , Sosman Jeffrey , Kirkwood John M. , Gajewski Thomas F. , Redman Bruce , Pavlov Dmitri , Bulanhagui Cecile , Bozon Viviana A. , Gomez-Navarro Jesus , Ribas Antoni 
Published: January 2009

PurposeCytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development.Patients and MethodsTwenty-eight patients with metastatic melanoma received monthly intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to determine recommended monthly phase II dose. During phase II, 89 patients received tremelimumab 10 mg/kg once every month or 15 mg/kg every 3 months.ResultsNo dose-limiting toxicity was observed in phase I once every month dosing. In phase II, 8 (10%) of 84 response-assessable patients attained objective antitumor responses; best overall objective response was one complete response and three partial responses in each dosing regimen. Most responses were durable (range, 3 to 30+ months). Most frequent treatment-related adverse events (AEs) were diarrhea, rash, and pruritus. Frequency of grade 3/4 AEs was 13% in the 15 mg/kg every 3 months arm and 27% in the 10 mg/kg once every month. Serious AEs were also less frequent in the 15 mg/kg once every 3 months cohort (9% v 23% in 10 mg/kg arm).ConclusionMultiple infusions of tremelimumab were generally tolerable and demonstrated single-agent antitumor activity. Both phase II regimens generated durable tumor responses. Based on its more favorable safety profile, 15 mg/kg every 3 months was selected for further clinical testing.
US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy
Authors: Ajani Jaffer A. , Winter Kathryn A. , Gunderson Leonard L. , Pedersen John , Benson Al B. , Thomas Charles R. , Mayer Robert J. , Haddock Michael G. , Rich Tyvin A. , Willett Christopher G. 
Published: January 2009

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma.
Synthesis and Photophysical Properties of Tris-bridged [3.3.n](3,6,9)Carbazolophanes
Authors: Tani Keita , Sakumoto Naoki , Kubono Koji , Hori Kazushige , Tohda Yasuo , Benten Hiroaki , Ohkita Hideo , Ito Shinzaburo , Yamamoto Masahide 
Published: January 2009

Abstract
Tris-bridged [3.3.n](3,6,9)carbazolophanes 1n (n=3–6), which are appropriate model compounds for fully overlapped excimer in carbazole chromophore, have been synthesized and characterized by NMR, X-ray, absorption and fluorescence spectra; 1n showed excimeric fluorescence, whose emission maxima strongly depended on the angles and distances between carbazole rings.
Monolayer Formation of a Pt–Ru Dinuclear Complex on a Gold (111) Surface and Its Conversion to a Pt–Ru Two-dimensional Nanocomposite Having Electrocatalytic Activity
Authors: Uehara Hiromitsu , Okawa Yukihisa , Sasaki Yoichi , Uosaki Kohei 
Published: January 2009

Abstract
Monolayers of Pt–Ru hetero-dinuclear complex were prepared on a Au(111) surface to obtain a designed two-dimensional Pt–Ru nanocomposite that acts as electrocatalyst for methanol oxidation reaction in alkaline solution.
The Structure and Absolute Stereochemistry of Briaexcavatin U, a New Chlorinated Briarane from a Cultured Octocoral Briareum excavatum
Authors: Sung Ping-Jyun , Lin Mei-Ru , Chiang Michael Y 
Published: January 2009

Abstract
A new chlorinated briarane, briaexcavatin U (1), has been isolated from a cultured octocoral Briareum excavatum. The structure, including the absolute stereochemistry of 1 was elucidated by spectroscopic methods and further confirmed by X-ray data analysis.
Heterogeneous Learning and the Targeting of Marketing Communication for New Products
Authors: Narayanan Sridhar , Manchanda Puneet 
Published: January 2009

New product launches are often accompanied by extensive marketing communication campaigns. Firms' allocation decisions for these marketing communication expenditures have two dimensions—across consumers and over time. This allocation problem is different relative to the problem of allocation of resources for existing products. In the case of new products, consumers are uncertain about their quality and learn about the products through marketing communication. Furthermore, different consumers may have different rates of learning about product quality; i.e., there may be heterogeneous learning. Thus, consumer responsiveness to marketing communication could vary along two dimensions. For each consumer, this responsiveness would vary over time, as she learns about product quality. Across consumers, there would be differences in responsiveness in each time period. For optimal allocation of marketing communication across both consumers and time, firms would need estimates of how consumer responsiveness varies across consumers and over time. Past studies have typically focused on one of these two dimensions in which responsiveness varies. They have either looked at heterogeneity in responsiveness across agents or the variation in responsiveness over time. In the context of new products, past research has looked at how consumer learning about product quality causes responsiveness to vary over time. In this study, we build a model that allows for heterogeneous learning rates and obtain individual-level learning parameters for each consumer. We use a novel and rich panel data set that allows us to estimate these model parameters.To obtain individual-level estimates of learning, we add a hierarchical Bayesian structure to the Bayesian learning model. We exploit the natural hierarchy in the Bayesian learning process to incorporate it in the hierarchical Bayesian model. We use data augmentation, coupled with the Metropolis-Hastings algorithm, to make inferences about individual-level parameters of learning. We conduct this analysis on a unique panel data set of physicians where we observe prescription decisions and detailing (i.e., sales-force effort) at the individual physician level for a new prescription drug category.Our results show that there is significant heterogeneity across physicians in their rates of learning about the quality of new drugs. We also find that there are asymmetries in the temporal evolution of responsiveness of physicians to detailing—physicians who are more responsive to detailing in early periods are less responsive later on and vice versa. These findings have interesting implications for the targeting of detailing across physicians and over time. We find that firms could increase their revenue if they took these temporal and cross-sectional differences in responsiveness into account while deciding on allocations of detailing.
Grandidentatin isomer from bark of suwon poplar (Populus alba L.×Populus glandulosa Uyeki)
Authors: Kim Jin-Kyu , Bae Young-Soo 
Published: January 2009

Abstract
The phenolic glucoside cis-2-hydroxycyclohexyl 6-O-p-coumaroyl-β-d-glucopyranoside was isolated from the bark of the hybrid poplar Populus alba×glandulosa by column chromatography over Sephadex LH-20 and Silica gel preparative TLC. The structure elucidation was performed by NMR spectroscopy (2D NMR COSY, DEPT, HMQC, and HMBC) and MS spectrometry.
Modification of lignin with laccases for the adsorption of anionic ferulic acid studied by quartz cristall microbalance with dissipation and AFM
Authors: Saarinen Terhi , Suurnäkki Anna , Österberg Monika , Laine Janne 
Published: January 2009

Abstract
The adsorption of laccases and ferulic acid on a lignin substrate has been studied using a quartz crystal microbalance with dissipation (QCM-D) and an atomic force microscope (AFM). Two different additional strategies were applied: ferulic acid was added after laccase pretreatment, or coadsorbed together with laccase. The effect of two laccases isolated from Trametes hirsuta and Melanocarpus albomyces was compared on lignin activation. The QCM-D results were also compared against bulk experiments on chemithermomechanical pulp. The two laccases affected the adsorption of ferulic acid differently. Adsorption of T. hirsuta laccase was not observed, while the adsorption of M. albomyces laccase was obvious. However, both laccases still activated lignin and the amount of ferulic acid adsorbed was significantly higher on laccase-activated lignin than on the non-activated one. Rinsing after activation removed some slightly bound laccase from the substrate and decreased the adsorbed amount of subsequently added ferulic acid. Interestingly, only T. hirsuta laccase could catalyse the lasting attachment of polymerised ferulic acid onto lignin. The QCM-D and AFM results correlated with the findings of studies concerning bonding of ferulic acid on chemithermomechanical pulp. Thus, this approach is useful in studying the behaviour of enzymes on lignin substrates.
Mystéres limpides: Time and Transformation in Debussy's Des pas sur la neige
Authors: Rings Steven 
Published: January 2009

Abstract
Vladimir Jankélévitch heard Debussy's music as a sonic manifestation of certain nuclear mysteries of existence: mysteries of death, destiny, anguish, pleasure, love, space, and—in various forms—time. To describe these mysteries, he developed the paradoxical locution of the mystére limpide, the “lucid mystery.” Debussy's mysteries are lucid, Jankélévitch argued, in that they are not hidden behind arcane codes or hermetic formalisms, but are instead palpably present to experience, sensually manifest in the music's sounding surface. As such, they prove resistant to hermeneutic and analytical attention, which, per Jankélévitch, seek always to penetrate beyond sounding surfaces in search of hidden meanings.
This article takes Jankélévitch's ideas as a point of departure in both a positive and negative sense, adopting his notion of the mystére limpide as a valuable heuristic in Debussy study, but challenging his highly limited views of analysis and hermeneutics. The article takes as its focus Debussy's Prélude Des pas sur la neige and explores the ways in which it can be heard to manifest mystéres of time, representation, and consciousness. It does this, however, with the aid of analysis and hermeneutics, drawing on transformational theory, familiar concepts from narratology, and Proustian notions of memory. In short, the article deploys discourses anathema to Jankélévitch for decidedly Jankélévitchian ends. The conclusion explores the degrees to which such a paradoxical effort succeeds, ultimately arguing that discursive intervention—technical or otherwise—need not be a means of seeking out hidden meanings, but can instead be a means of drawing us closer to music as a physical, material phenomenon.
Smallness for gestational age interacts with high mobility group A2 gene genetic variation to modulate height
Authors: Bouatia-Naji Nabila , Marchand Marion , Cavalcanti-Proença Christine , Daghmoun Samia , Durand Emmanuelle , Tichet Jean , Marre Michel , Balkau Beverley , Froguel Philippe , Lévy-Marchal Claire 
Published: January 2009

ObjectiveHeight variability is largely under genetic control, although identifying the genetic variants involved has been until recently challenging. Smallness for gestational age (SGA) is a risk factor for adult short stature. Genome-wide association studies have identified a single nucleotide polymorphism (SNP) (rs1042725) in the high mobility group A2 gene (HMGA2) that consistently associates with height variability but its interaction with SGA is unknown.DesignWe assess the contribution of rs1042725 SNP and height variability in a French population and the impact of rs1042725 on SGA status at birth and height at adulthood in SGA individuals.MethodsWe genotyped rs1042725 in 4710 healthy participants from the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) cohort, 743 normal birth weight and 660 SGA individuals from the Haguenau study.Resultsrs1042725 is associated with increased height in the cohort participants (0.36 cm 95% CI (0.12–0.61) per C allele, P=0.004) but not with the SGA status or birth length. Interestingly, rs1042725 had a stronger effect on height in SGA participants (0.94 cm 95% CI (0.24–1.64) per C allele, P=0.009), especially in men (1.45 cm 95% CI (0.44–2.46) per C allele, P=0.005) in whom rs1042725 may explain 3% of height variability. SGA men carrying at least one C allele copy experienced more frequent catch-up in height (Padd=0.07; Pdom=0.03).ConclusionsOur study supports further the contribution of HMGA2 rs1042725 to height variability in European populations and shows an increased effect on height in SGA individuals where this variant favors height catch-up.
Effects of Genetic and Environmental Factors on Trait Network Predictions From Quantitative Trait Locus Data
Authors: Remington David L 
Published: January 2009

AbstractThe use of high-throughput genomic techniques to map gene expression quantitative trait loci has spurred the development of path analysis approaches for predicting functional networks linking genes and natural trait variation. The goal of this study was to test whether potentially confounding factors, including effects of common environment and genes not included in path models, affect predictions of cause–effect relationships among traits generated by QTL path analyses. Structural equation modeling (SEM) was used to test simple QTL-trait networks under different regulatory scenarios involving direct and indirect effects. SEM identified the correct models under simple scenarios, but when common-environment effects were simulated in conjunction with direct QTL effects on traits, they were poorly distinguished from indirect effects, leading to false support for indirect models. Application of SEM to loblolly pine QTL data provided support for biologically plausible a priori hypotheses of QTL mechanisms affecting height and diameter growth. However, some biologically implausible models were also well supported. The results emphasize the need to include any available functional information, including predictions for genetic and environmental correlations, to develop plausible models if biologically useful trait network predictions are to be made.
The Control Region of Maternally and Paternally Inherited Mitochondrial Genomes of Three Species of the Sea Mussel Genus Mytilus
Authors: Cao Liqin , Ort Brian S , Mizi Athanasia , Pogson Grant , Kenchington Elen , Zouros Eleftherios , Rodakis George C 
Published: January 2009

AbstractSpecies of the mussel genus Mytilus possess maternally and paternally transmitted mitochondrial genomes. In the interbreeding taxa Mytilus edulis and M. galloprovincialis, several genomes of both types have been fully sequenced. The genome consists of the coding part (which, in addition to protein and RNA genes, contains several small noncoding sequences) and the main control region (CR), which in turn consists of three distinct parts: the first variable (VD1), the conserved (CD), and the second variable (VD2) domain. The maternal and paternal genomes are very similar in gene content and organization, even though they differ by &gt;20% in primary sequence. They differ even more at VD1 and VD2, yet they are remarkably similar at CD. The complete sequence of a genome from the closely related species M. trossulus was previously reported and found to consist of a maternal-like coding part and a paternal-like and a maternal-like CR. From this and from the fact that it was extracted from a male individual, it was inferred that this is a genome that switched from maternal to paternal transmission. Here we provide clear evidence that this genome is the maternal genome of M. trossulus. We have found that in this genome the tRNAGln in the coding region is apparently defective and that an intact copy of this tRNA occurs in the CR, that one of the two conserved domains is missing essential motifs, and that one of the two first variable domains has a high rate of divergence. These features may explain the large size and mosaic structure of the CR of the maternal genome of M. trossulus. We have also obtained CR sequences of the maternal and paternal genomes of M. californianus, a more distantly related species. We compare the control regions from all three species, focusing on the divergence among genomes of different species origin and among genomes of different transmission routes.
Rhythmic Conidiation in Constant Light inVividMutants ofNeurospora crassa
Authors: Schneider Kevin , Perrino Sabrina , Oelhafen Kim , Li Sanshu , Zatsepin Artiom , Lakin-Thomas Patricia , Brody Stuart 
Published: January 2009

AbstractIn Neurospora crassa, a circadian rhythm of conidiation (asexual spore formation) can be seen on the surface of agar media. This rhythm has a period of 22 hr in constant darkness (D/D). Under constant illumination (L/L), no rhythm is visible and cultures show constant conidiation. However, here we report that strains with a mutation in the vivid (vvd) gene, previously shown to code for the photoreceptor involved in photo-adaptation, exhibit conidiation rhythms in L/L as well as in D/D. The period of the rhythm of vvd strains ranges between 6 and 21 hr in L/L, depending upon the intensity of the light, the carbon source, and the presence of other mutations. Temperature compensation of the period also depends on light intensity. Dark pulses given in L/L shift the phase of the rhythm. Shifts from L/L to D/D show unexpected after effects; i.e., the short period of a vvd strain in L/L gradually lengthens over 2–3 days in D/D. The rhythm in L/L requires the white collar (wc-1) gene, but not the frequency (frq) gene. FRQ protein shows no rhythm in L/L in a vvd strain. The conidiation rhythm in L/L in vvd is therefore driven by a FRQ-less oscillator (FLO).
Hierarchical Generalized Linear Models for Multiple Quantitative Trait Locus Mapping
Authors: Yi Nengjun , Banerjee Samprit 
Published: January 2009

AbstractWe develop hierarchical generalized linear models and computationally efficient algorithms for genomewide analysis of quantitative trait loci (QTL) for various types of phenotypes in experimental crosses. The proposed models can fit a large number of effects, including covariates, main effects of numerous loci, and gene–gene (epistasis) and gene–environment (G × E) interactions. The key to the approach is the use of continuous prior distribution on coefficients that favors sparseness in the fitted model and facilitates computation. We develop a fast expectation-maximization (EM) algorithm to fit models by estimating posterior modes of coefficients. We incorporate our algorithm into the iteratively weighted least squares for classical generalized linear models as implemented in the package R. We propose a model search strategy to build a parsimonious model. Our method takes advantage of the special correlation structure in QTL data. Simulation studies demonstrate reasonable power to detect true effects, while controlling the rate of false positives. We illustrate with three real data sets and compare our method to existing methods for multiple-QTL mapping. Our method has been implemented in our freely available package R/qtlbim (www.qtlbim.org), providing a valuable addition to our previous Markov chain Monte Carlo (MCMC) approach.
Value of Imaging Studies After a First Febrile Urinary Tract Infection in Young Children: Data From Italian Renal Infection Study 1
Authors: Montini Giovanni , Zucchetta Pietro , Tomasi Lisanna , Talenti Enrico , Rigamonti Waifro , Picco Giorgio , Ballan Alberto , Zucchini Andrea , Serra Laura , Canella Vanna , Gheno Marta , Venturoli Andrea , Ranieri Marco , Caddia Valeria , Carasi Carla , Dall'Amico Roberto , Hewitt Ian 
Published: January 2009

OBJECTIVE. We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection.METHODS. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children ≤2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans.RESULTS. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring.CONCLUSIONS. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.