bluuebunny/crossref_metadata_2025_split huggingface dataset:
Links between analysis of surrogate endpoints and endogeneity
Authors: Ghosh Debashis , Elliott Michael R. , Taylor Jeremy M. G. 
Published: August 2010

AbstractThere has been substantive interest in the assessment of surrogate endpoints in medical research. These are measures that could potentially replace ‘true’ endpoints in clinical trials and lead to studies that require less follow‐up. Recent research in the area has focused on assessments using causal inference frameworks. Beginning with a simple model for associating the surrogate and true endpoints in the population, we approach the problem as one of endogenous covariates. An instrumental variables estimator and general two‐stage algorithm are proposed. Existing surrogacy frameworks are then evaluated in the context of the model. In addition, we define an extended relative effect estimator as well as a sensitivity analysis for assessing what we term the treatment instrumentality assumption. A numerical example is used to illustrate the methodology. Copyright © 2010 John Wiley & Sons, Ltd.
An easy‐to‐implement approach for analyzing case–control and case‐only studies assuming gene–environment independence and Hardy–Weinberg equilibrium
Authors: Lee Wen‐Chung , Wang Liang‐Yi , Cheng K. F. 
Published: August 2010

AbstractThe case–control study is a simple and an useful method to characterize the effect of a gene, the effect of an exposure, as well as the interaction between the two. The control‐free case‐only study is yet an even simpler design, if interest is centered on gene–environment interaction only. It requires the sometimes plausible assumption that the gene under study is independent of exposures among the non‐diseased in the study populations. The Hardy–Weinberg equilibrium is also sometimes reasonable to assume. This paper presents an easy‐to‐implement approach for analyzing case–control and case‐only studies under the above dual assumptions. The proposed approach, the ‘conditional logistic regression with counterfactuals’, offers the flexibility for complex modeling yet remains well within the reach to the practicing epidemiologists. When the dual assumptions are met, the conditional logistic regression with counterfactuals is unbiased and has the correct type I error rates. It also results in smaller variances and achieves higher powers as compared with using the conventional analysis (unconditional logistic regression). Copyright © 2010 John Wiley & Sons, Ltd.
Sequential generalized likelihood ratio tests for vaccine safety evaluation
Authors: Shih Mei‐Chiung , Lai Tze Leung , Heyse Joseph F. , Chen Jie 
Published: August 2010

AbstractThe evaluation of vaccine safety involves pre‐clinical animal studies, pre‐licensure randomized clinical trials, and post‐licensure safety studies. Sequential design and analysis are of particular interest because they allow early termination of the trial or quick detection that the vaccine exceeds a prescribed bound on the adverse event rate. After a review of the recent developments in this area, we propose a new class of sequential generalized likelihood ratio tests for evaluating adverse event rates in two‐armed pre‐licensure clinical trials and single‐armed post‐licensure studies. The proposed approach is illustrated using data from the Rotavirus Efficacy and Safety Trial. Simulation studies of the performance of the proposed approach and other methods are also given. Copyright © 2010 John Wiley & Sons, Ltd.
Interval estimation of quantile ratios applied to anti‐cancer drug screening by xenograft experiments
Authors: Cheng Cheng , Wu Jianrong 
Published: August 2010

AbstractThe current practice in analyzing data from anti‐cancer drug screening by xenograft experiments lacks statistical consideration to account for experimental noise, and a sound inference procedure is necessary. A novel confidence bound and interval procedure for estimating quantile ratios developed in this paper fills the void. Justified by rigorous large‐sample theory and a simulation study of small‐sample performance, the proposed method performs well in a wide range of scenarios involving right‐skewed distributions. By providing rigorous inference and much more interpretable statistics that account for experimental noise, the proposed method improves the current practice of analyzing drug activity data in xenograft experiments. The proposed method is fully nonparametric, simple to compute, performs equally well or better than known nonparametric methods, and is applicable to any statistical inference of a ‘fold change’ that can be formulated as a quantile ratio. Copyright © 2010 John Wiley & Sons, Ltd.
A Runx1 Intronic Enhancer Marks Hemogenic Endothelial Cells and Hematopoietic Stem Cells
Authors: Ng Cherry Ee Lin , Yokomizo Tomomasa , Yamashita Namiko , Cirovic Branko , Jin Hao , Wen Zilong , Ito Yoshiaki , Osato Motomi 
Published: August 2010

Abstract
Runx1 is essential for the generation of hematopoietic stem cells (HSCs) and is frequently mutated in human leukemias. However, the cis-regulatory mechanisms modulating the Runx1 gene expression remain to be elucidated. Herewith, we report the identification of an intronic Runx1 enhancer, Runx1 +24 mouse conserved noncoding element (mCNE), using a combinatorial in silico approach involving comparative genomics and retroviral integration sites mapping. The Runx1 +24 mCNE was found to possess hematopoietic-specific enhancer activity in both zebrafish and mouse models. Significantly, this enhancer is active specifically in hemogenic endothelial cells (ECs) at sites where the de novo generation of HSCs occurs. The activity of this enhancer is also strictly restricted to HSCs within the hematopoietic compartment of the adult bone marrow. We anticipate that Runx1 +24 mCNE HSC enhancer will serve as a molecular handle for tracing and/or manipulating hemogenic ECs/HSCs behavior in vivo, and consequently become an invaluable tool for research on stem cell and cancer biology.
ETV5 Regulates Sertoli Cell Chemokines Involved in Mouse Stem/Progenitor Spermatogonia Maintenance
Authors: Simon Liz , Ekman Gail C. , Garcia Thomas , Carnes Kay , Zhang Zhen , Murphy Theresa , Murphy Kenneth M. , Hess Rex A. , Cooke Paul S. , Hofmann Marie-Claude 
Published: August 2010

AbstractSpermatogonial stem cells are the only stem cells in the body that transmit genetic information to offspring. Although growth factors responsible for self-renewal of these cells are known, the factors and mechanisms that attract and physically maintain these cells within their microenvironment are poorly understood. Mice with targeted disruption of Ets variant gene 5 (Etv5) show total loss of stem/progenitor spermatogonia following the first wave of spermatogenesis, resulting in a Sertoli cell-only phenotype and aspermia. Microarray analysis of primary Sertoli cells from Etv5 knockout (Etv5−/−) versus wild-type (WT) mice revealed significant decreases in expression of several chemokines. Chemotaxis assays demonstrated that migration of stem/progenitor spermatogonia toward Etv5−/− Sertoli cells was significantly decreased compared to migration toward WT Sertoli cells. Interestingly, differentiating spermatogonia, spermatocytes, and round spermatids were not chemoattracted by WT Sertoli cells, whereas stem/progenitor spermatogonia showed a high and significant chemotactic index. Rescue assays using recombinant chemokines indicated that C-C-motif ligand 9 (CCL9) facilitates Sertoli cell chemoattraction of stem/progenitor spermatogonia, which express C-C-receptor type 1 (CCR1). In addition, there is protein-DNA interaction between ETV5 and Ccl9, suggesting that ETV5 might be a direct regulator of Ccl9 expression. Taken together, our data show for the first time that Sertoli cells are chemoattractive for stem/progenitor spermatogonia, and that production of specific chemokines is regulated by ETV5. Therefore, changes in chemokine production and consequent decreases in chemoattraction by Etv5−/− Sertoli cells helps to explain stem/progenitor spermatogonia loss in Etv5−/− mice.
Myoblast-Derived Neuronal Cells Form Glutamatergic Neurons in the Mouse Cerebellum
Authors: Gopalakrishnan Vidya , Bie Bihua , Sinnappah-Kang Neeta D. , Adams Henry , Fuller Gregory N. , Pan Zhizhong Z. , Majumder Sadhan 
Published: August 2010

AbstractProduction of neurons from non-neural cells has far-reaching clinical significance. We previously found that myoblasts can be converted to a physiologically active neuronal phenotype by transferring a single recombinant transcription factor, REST-VP16, which directly activates target genes of the transcriptional repressor, REST. However, the neuronal subtype of M-RV cells and whether they can establish synaptic communication in the brain have remained unknown. M-RV cells engineered to express green fluorescent protein (M-RV-GFP) had functional ion channels but did not establish synaptic communication in vitro. However, when transplanted into newborn mice cerebella, a site of extensive postnatal neurogenesis, these cells expressed endogenous cerebellar granule precursors and neuron proteins, such as transient axonal glycoprotein-1, neurofilament, type-III β-tubulin, superior cervical ganglia-clone 10, glutamate receptor-2, and glutamate decarboxylase. Importantly, they exhibited action potentials and were capable of receiving glutamatergic synaptic input, similar to the native cerebellar granule neurons. These results suggest that M-RV-GFP cells differentiate into glutamatergic neurons, an important neuronal subtype, in the postnatal cerebellar milieu. Our findings suggest that although activation of REST-target genes can reprogram myoblasts to assume a general neuronal phenotype, the subtype specificity may then be directed by the brain microenvironment.
Effect of steady deflections on the aeroelastic stability of a turbine blade
Authors: Kallesøe B. S. 
Published: August 2010

AbstractThis paper deals with effects of geometric non‐linearities on the aeroelastic stability of a steady‐state deflected blade. Today, wind turbine blades are long and slender structures that can have a considerable steady‐state deflection which affects the dynamic behaviour of the blade. The flapwise blade deflection causes the edgewise blade motion to couple to torsional blade motion and thereby to the aerodynamics through the angle of attack. The analysis shows that in the worst case for this particular blade, the edgewise damping can be decreased by half. Copyright © 2010 John Wiley & Sons, Ltd.
Evaluation of the effects of turbulence model enhancements on wind turbine wake predictions
Authors: Prospathopoulos J. M. , Politis E. S. , Rados K. G. , Chaviaropoulos P. K. 
Published: August 2010

AbstractThe modelling of wind turbine wakes is investigated in this paper using a Navier–Stokes solver employing the k–ω turbulence model appropriately modified for atmospheric flows. It is common knowledge that even single‐wind turbine wake predictions with computational fluid dynamic methods underestimate the near wake deficit, directly contributing to the overestimation of the power of the downstream turbines. For a single‐wind turbine, alternative modelling enhancements under neutral and stable atmospheric conditions are tested in this paper to account for and eventually correct the turbulence overestimation that is responsible for the faster flow recovery that appears in the numerical predictions. Their effect on the power predictions is evaluated with comparison with existing wake measurements. A second issue addressed in this paper concerns multi‐wake predictions in wind farms, where the estimation of the reference wind speed that is required for the thrust calculation of a turbine located in the wake(s) of other turbines is not obvious. This is overcome by utilizing an induction factor‐based concept: According to it, the definition of the induction factor and its relationship with the thrust coefficient are employed to provide an average wind speed value across the rotor disk for the estimation of the axial force. Application is made on the case of five wind turbines in a row. Copyright © 2010 John Wiley & Sons, Ltd.
Trellis display
Authors: Robbins Naomi B. 
Published: August 2010

AbstractDisplaying data with three or more dimensions effectively on a two‐dimensional paper or screen is not an easy task. Commonly used graphs such as pie charts and bar graphs do not allow for easy comparisons across all variables. This article discusses trellis display, a framework for the visualization of data through multiple panels organized in rows, columns, and pages. Each panel displays some of the variables with the values of the other variables held fixed. We demonstrate the effectiveness of trellis display by comparing identical sets of data first using traditional pie charts or bar graphs and then using trellis display. In all cases, the trellis figures show characteristics of the data more clearly than the more common graphs do. We discuss additional advantages of trellis display such as the ability of trellis figures to distinguish variables without the use of color. Copyright © 2010 John Wiley & Sons, Inc.This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Statistical Graphics and Visualization
Genome‐wide screen of Saccharomyces cerevisiae for killer toxin HM‐1 resistance
Authors: Miyamoto Masahiko , Furuichi Yasuhiro , Komiyama Tadazumi 
Published: August 2010

AbstractWe screened a set of Saccharomyces cerevisiae deletion mutants for resistance to killer toxin HM‐1, which kills susceptible yeasts through inhibiting 1,3‐beta‐glucan synthase. By using HM‐1 plate assay, we found that eight gene‐deletion mutants had higher HM‐1‐resistance compared with the wild‐type. Among these eight genes, five—ALG3, CAX4, MNS1, OST6 and YBL083C—were associated with N‐glycan formation and maturation. The ALG3 gene has been shown before to be highly resistant to HM‐1. The YBL083C gene may be a dubious open reading frame that overlaps partially the ALG3 gene. The deletion mutant of the MNS1 gene that encodes 1,2‐alpha‐mannosidase showed with a 13‐fold higher HM‐1 resistance compared with the wild‐type. By HM‐1 binding assay, the yeast plasma membrane fraction of alg3 and mns1 cells had less binding ability compared with wild‐type cells. These results indicate that the presence of the terminal 1,3‐alpha‐linked mannose residue of the B‐chain of the N‐glycan structure is essential for interaction with HM‐1. A deletion mutant of aquaglyceroporin Fps1p also showed increased HM‐1 resistance. A deletion mutant of osmoregulatory mitogen‐activated protein kinase Hog1p was more sensitive to HM‐1, suggesting that high‐osmolarity glycerol pathways plays an important role in the compensatory response to HM‐1 action. Copyright © 2010 John Wiley & Sons, Ltd.
Metabolic regulation rather than de novo enzyme synthesis dominates the osmo‐adaptation of yeast
Authors: Bouwman Jildau , Kiewiet José , Lindenbergh Alexander , van Eunen Karen , Siderius Marco , Bakker Barbara M. 
Published: August 2010

AbstractIntracellular accumulation of glycerol is essential for yeast cells to survive hyperosmotic stress. Upon hyperosmotic stress the gene expression of enzymes in the glycerol pathway is strongly induced. Recently, however, it was shown that this gene‐expression response is not essential for survival of an osmotic shock [Mettetal JT et al. (2008) Science 319: 482–484 and Westfall PJ et al. (2008) Proc Natl Acad Sci 105: 12212–12217]. Instead, pure metabolic adaptation can rescue the yeast. The existence of two alternative mechanisms urged the question which of these mechanisms dominates time‐dependent adaptation of wild‐type yeast to osmotic stress under physiological conditions. The regulation of the glycerol pathway was analysed in aerobic, glucose‐limited cultures upon addition of 1 M of sorbitol, leading to a hyperosmotic shock. In agreement with earlier studies, the mRNA levels of the glycerol‐producing enzymes as well as their catalytic capacities increased. Qualitatively this induction followed a similar time course to the increase of the glycerol flux. However, a quantitative regulation analysis of the data revealed an initial regulation by metabolism alone. After only a few minutes gene expression came into play, but even after an hour, 80% of the increase in the glycerol flux was explained by metabolic changes in the cell, and 20% by induction of gene expression. This demonstrates that the novel metabolic mechanism is not just a secondary rescue mechanism, but the most important mechanism to regulate the glycerol flux under physiological conditions. Copyright © 2010 John Wiley & Sons, Ltd.
Contact problems for several transversely isotropic elastic layers bonded to an elastic half‐space
Authors: Fabrikant V.I. 
Published: August 2010

AbstractThe idea of generalized images, first used by the author for the case of crack problems, is applied here to solve a contact problem forntransversely isotropic elastic layers, bonded to each other and to an elastic half‐space, made of a different transversely isotropic material. A rigid punch of arbitrary shape is pressed against the top layer's free surface. The governing integral equation is derived for the case of two layers; it is mathematically equivalent to that of an electrostatic problem of an infinite row of coaxial charge disks in the shape of the domain of contact. This result is then generalized for an arbitrary number of layers. As a comparison, the method of integral transforms is also used to solve the problem. The main difference of our integral transform approach with the existing ones is in separating of our half‐space solution from the integral transform terms. It is shown that both methods lead to the same results, thus giving a new interpretation to the integral transform as a sum of an infinite series of generalized images.
Colorectal Cancer in Young Patients in Israel: A Distinct Clinicopathological Entity?
Authors: Shemesh‐Bar L. , Kundel Y. , Idelevich E. , Sulkes J. , Sulkes A. , Brenner B. 
Published: August 2010

AbstractPurposeThis study was designed to characterize the entity of colorectal cancer (CRC) in young patients and to evaluate whether it has any unique epidemiological or clinicopathological features.MethodsThe study population consisted of all consecutive young (≤50 years old at diagnosis) patients with CRC who were diagnosed during the years 1997–2007 and were treated at our institution, and a matching group of patients (>50 years at diagnosis). The medical files of these patients were reviewed, and the epidemiological, clinical, and pathological features of both groups were compared.ResultsThere were 406 patients: 203 in each group. The features of the older group were typical for patients with CRC, but the younger group showed female predominance, different ethnic composition, prevalence of family history of cancer and hereditary CRC syndromes, and lower incidence of polyps. The incidence of left‐sided tumors and advanced stages (III–IV) at diagnosis was higher in the younger patients. Mucinous/signet ring histology, grade, stage, lymphatic and vascular invasion were all predictive of survival, whereas age was not.ConclusionsColorectal cancer in young patients was found to display a cluster of unique characteristics but fewer than previously reported and young age by itself was not found to impact patient outcome.
Building a 2010 biodiversity conservation data baseline: contributions of the Group on Earth Observations
Authors: Muchoney Douglas M. , Williams Michael 
Published: August 2010

AbstractCharacterizing, modeling, and monitoring the distribution and condition of the Earth's biodiversity and ecosystems has a long history of being aided by Earth Observation data and the models and derivative products that they support. At the global scale, there need to be more coordinated efforts to acquire, process, analyze, and make available these observation data across all disciplines, particularly since many applications use the same primary and derived data. Towards that end, the Group on Earth Observations (GEO) is implementing the Global Earth Observing System of Systems. The purpose of this article is to provide information on GEO's goals and activities relevant to biodiversity and ecosystems. The article also describes the data that would best serve as a year 2010 baseline in order to support the objectives of the Convention on Biological Diversity (CBD) as well as many other international agreements, programs, and activities. Indeed, an assessment of existing biodiversity observations with a concomitant recognition of the remaining gaps will promote the establishment of an integrated framework for biodiversity observations in support of the CBD's efforts.
Design and Fabrication of Fiber-Optic Nanoprobes for Optical Sensing
Authors: Zhang Yan , Dhawan Anuj , Vo-Dinh Tuan 
Published: August 2010

AbstractThis paper describes the design and fabrication of fiber-optic nanoprobes developed for optical detection in single living cells. It is critical to fabricate probes with well-controlled nanoapertures for optimized spatial resolution and optical transmission. The detection sensitivity of fiber-optic nanoprobe depends mainly on the extremely small excitation volume that is determined by the aperture sizes and penetration depths. We investigate the angle dependence of the aperture in shadow evaporation of the metal coating onto the tip wall. It was found that nanoaperture diameters of approximately 50 nm can be achieved using a 25° tilt angle. On the other hand, the aperture size is sensitive to the subtle change of the metal evaporation angle and could be blocked by irregular metal grains. Through focused ion beam (FIB) milling, optical nanoprobes with well-defined aperture size as small as 200 nm can be obtained. Finally, we illustrate the use of the nanoprobes by detecting a fluorescent species, benzo[a]pyrene tetrol (BPT), in single living cells. A quantitative estimation of the numbers of BPT molecules detected using fiber-optic nanoprobes for BPT solutions shows that the limit of detection was approximately 100 molecules.
Biomagnetic of Apatite-Coated Cobalt Ferrite: A Core–Shell Particle for Protein Adsorption and pH-Controlled Release
Authors: Tang I-Ming , Krishnamra Nateetip , Charoenphandhu Narattaphol , Hoonsawat Rassmidara , Pon-On Weeraphat 
Published: August 2010

AbstractMagnetic nanoparticle composite with a cobalt ferrite (CoFe2O4, (CF)) core and an apatite (Ap) coating was synthesized using a biomineralization process in which a modified simulated body fluid (1.5SBF) solution is the source of the calcium phosphate for the apatite formation. The core–shell structure formed after the citric acid–stabilized cobalt ferrite (CFCA) particles were incubated in the 1.5 SBF solution for 1 week. The mean particle size of CFCA-Ap is about 750 nm. A saturation magnetization of 15.56 emug-1 and a coercivity of 1808.5 Oe were observed for the CFCA-Ap obtained. Bovine serum albumin (BSA) was used as the model protein to study the adsorption and release of the proteins by the CFCA-Ap particles. The protein adsorption by the CFCA-Ap particles followed a more typical Freundlich than Langmuir adsorption isotherm. The BSA release as a function of time became less rapid as the CFCA-Ap particles were immersed in higher pH solution, thus indicating that the BSA release is dependent on the local pH.