bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of a triple‐gene knockout mammalian cell line using engineered zinc‐finger nucleases
Authors: Liu Pei‐Qi , Chan Edmond M. , Cost Gregory J. , Zhang Lin , Wang Jianbin , Miller Jeffrey C. , Guschin Dmitry Y. , Reik Andreas , Holmes Michael C. , Mott John E. , Collingwood Trevor N. , Gregory Philip D. 
Published: January 2010

AbstractMammalian cells with multi‐gene knockouts could be of considerable utility in research, drug discovery, and cell‐based therapeutics. However, existing methods for targeted gene deletion require sequential rounds of homologous recombination and drug selection to isolate rare desired events—a process sufficiently laborious to limit application to individual loci. Here we present a solution to this problem. Firstly, we report the development of zinc‐finger nucleases (ZFNs) targeted to cleave three independent genes with known null phenotypes. Mammalian cells exposed to each ZFN pair in turn resulted in the generation of cell lines harboring single, double, and triple gene knockouts, that is, the successful disruption of two, four, and six alleles. All three biallelic knockout events were obtained at frequencies of >1% without the use of selection, displayed the expected knockout phenotype(s), and harbored DNA mutations centered at the ZFN binding sites. These data demonstrate the utility of ZFNs in multi‐locus genome engineering. Biotechnol. Bioeng. 2010; 106: 97–105. © 2009 Wiley Periodicals, Inc.
Multiple testing using the posterior probabilities of directional alternatives, with application to genomic studies
Authors: Labbe Aurélie , Thompson Mary E. 
Published: January 2010

AbstractThis paper aims to connect Bayesian analysis and frequentist theory in the context of multiple comparisons. The authors show that when testing the equality of two sample means, the posterior probability of the one‐sided alternative hypothesis, defined as a half‐space, shares with the frequentist P‐value the property of uniformity under the null hypothesis. Ultimately, the posterior probability may thus be used in the same spirit as a P‐value in the Benjamini‐Hochberg procedure, or in any of its extensions.
Bootstrapping data with multiple levels of variation
Authors: Field Christopher A. , Pang Zhen , Welsh Alan H. 
Published: January 2010

AbstractThe authors consider general estimators for the mean and variance parameters in the random effect model and in the transformation model for data with multiple levels of variation. They show that these estimators have different distributions under the two models unless all the variables have Gaussian distributions. They investigate the asymptotic properties of bootstrap procedures designed for the two models. They also report simulation results and illustrate the bootstraps using data on red spruce trees.
Generational risks for cancers not related to tobacco, screening, or treatment in the United States
Authors: Han Yueh‐Ying , Davis Devra L. , Weissfeld Joel L. , Dinse Gregg E. 
Published: January 2010

AbstractBACKGROUND:To assess trends in cancer, the authors evaluated the risk of 1 generation compared with that 25 years earlier (generational risk) for 3 groupings of cancers: those related to tobacco; those that reflect advances in screening or treatment; and a residual category of all other cancers.METHODS:In individuals ages 20 years to 84 years, age‐period‐cohort models were used to summarize time trends in terms of generational risk and average annual percentage change for US cancer incidence (1975‐2004) and mortality (1970‐2004) rates associated with these 3 cancer groupings.RESULTS:Adult white men today developed 16% fewer tobacco‐related cancers and had 21% fewer deaths because of those cancers than their fathers' generation, whereas adult white women experienced increases of 28% and 19%, respectively, relative to their mothers. The incidence of commonly screened cancers rose 74% in men and 10% in women, whereas mortality fell 25% in men and 31% in women. For cancers that have not been linked chiefly to tobacco or screening, the incidence was 34% and 23% higher in white men and white women, respectively, than in their parents' generation 25 years earlier. Mortality in this residual category decreased 14% in men and 18% in women. Results among blacks were qualitatively similar to those among whites.CONCLUSIONS:Despite declining overall cancer death rates, adults are experiencing increased incidence of cancers that are not associated with tobacco or screening relative to their parents. Future research should examine whether similar patterns are exhibited in other modern nations and should identify population‐wide avoidable risks that could account for unexplained increases in these residual cancers. Cancer 2010. © 2010 American Cancer Society.
Inducing Spin Crossover in Amphiphilic Iron(III) Complexes
Authors: Martinho Paulo N. , Harding Charles J. , Müller‐Bunz Helge , Albrecht Martin , Morgan Grace G. 
Published: January 2010

AbstractThermal spin crossover (SCO) was induced in a high‐spin FeIII complex by alkylation of the polyamino ligand backbone. The SCO profile was responsive to chain length with partial crossover observed with C6 alkylation and full transition upon lengthening to C12. No crossover was observed when the backbone was unfunctionalised, and all three complexes were obtained as unsolvated tetrafluoroborate salts.
Synthesis and Structural Characterization of Planar Chiral Cr(CO)3‐Complexed Aromatic Nitrones – Valuable Substrates for Asymmetric SmI2‐Induced Coupling Reactions
Authors: Chavarot‐Kerlidou Murielle , Rivard Michaël , Chamiot Bénédicte , Hahn Franck , Rose‐Munch Françoise , Rose Eric , Py Sandrine , Herson Patrick 
Published: January 2010

AbstractThe synthesis of Cr(CO)3‐complexed aromatic nitrones 2 is reported. These new planar‐chiral complexes were fully characterized in solution by 1H and 13C NMR, IR and cyclic voltammetry. Moreover, structural data were obtained from X‐ray structures of nitrones 2b, 2d, 2e and 2f. These analyses converge to give evidence of a favoured anti conformation of ortho‐substituted nitrones, with an unusual N–O···Haryl intramolecular interaction forming a six‐membered ring. The reactivity of these chiral nitrones in SmI2‐induced pinacol‐type reactions was investigated. The reductive cross‐coupling of nitrones 2a–d with carbonyl compounds proved to be highly chemo‐ and diastereoselective and afforded precursors of enantioenriched β‐amino alcohols in excellent yields.
Synthesis of 5‐Heteroaryl‐ and 5,7‐Bis(heteroaryl)azulenes by Electrophilic Substitution of 1,3‐Di‐tert‐Butylazulene with Triflates of N‐Containing Heterocycles
Authors: Shoji Taku , Ito Shunji , Toyota Kozo , Morita Noboru 
Published: January 2010

AbstractAn efficient synthesis of 5‐heteroaryl‐ and 5,7‐bis(heteroaryl)azulene derivatives was established for first time. The reaction proceeded through electrophilic substitution of 1,3‐di‐tert‐butylazulene (1) with the triflates of N‐containing heterocycles, in the presence of excess heterocycles, in good yields. The presumed intermediates, 5‐(dihydroheteroaryl)azulene derivatives were also available by the reaction with several N‐containing heterocycles in the presence of Tf2O under milder reaction conditions. Treatment of the 5‐(dihydroheteroaryl)azulene derivatives with KOH readily gave the desired 5‐(heteroaryl)azulene derivatives. Unexpectedly, N‐(5‐azulenyl)pyridinium triflate 17 was also obtained by the reaction of 1 with (trifluoromethylsulfonyl)pyridinium trifluoromethanesulfonate (TPT). 5‐Heteroaryl‐ and 5,7‐bis(heteroaryl)azulene derivatives exhibited a significant color change in acetic acid compared to those in dichloromethane due to the development of intramolecular charge‐transfer (CT) absorption bands. The redox behavior of these new azulene derivatives was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV).
MVPACK: A package to calculate energy levels and magnetic properties of high nuclearity mixed valence clusters
Authors: Borrás‐Almenar J. J. , Cardona‐Serra S. , Clemente‐Juan J. M. , Coronado E. , Palii A. V. , Tsukerblat B.S. 
Published: December 2009

AbstractWe present a FORTRAN code based on a new powerful and efficient computational approach to solve the double exchange problem for high‐nuclearity MV clusters containing arbitrary number of localized spins and itinerant electrons. We also report some examples in order to show the possibilities of the program. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Transcriptional regulation of pro‐apoptotic Par‐4 by NF‐κB/p65 and its function in controlling cell kinetics during early events in endometrial tumourigenesis
Authors: Saegusa Makoto , Hashimura Miki , Kuwata Takeshi , Okayasu Isao 
Published: December 2009

AbstractProstatic apoptosis response‐4 (Par‐4) was first identified in prostatic cancer cells that were induced to undergo apoptosis. Recently, Par‐4 has been suggested to be a tumour suppressor gene that plays a role in the development of endometrial carcinomas (ECs), but the exact mechanism remains to be clarified. Here we examined gene activation signalling cascades and influence on cell kinetics during endometrial tumourigenesis. In normal endometrium, constitutively high levels of Par‐4 expression were observed in epithelial cells through the menstrual cycle, in contrast to the transient up‐regulation in stromal components in the menstrual stage, correlated positively with the phospho‐p65 (pp65) status and apoptosis. In contrast, most ECs exhibited significant down‐regulation as compared to normal endometrium, with positive links only to pp65 expression. In EC cell lines, transfection of the NF‐κB subunit p65 led to transactivation of Par‐4 through specific binding to its promoter region, in contrast to the suppression by active Akt, suggesting that the balance between the two signals may be important to determine Par‐4 expression levels. In addition, transient overexpression of Par‐4 resulted in the induction of not only apoptosis but also senescence, through changes in the expression of bcl‐2 and p21$^{{\rm WAF1}}$, respectively. Together, these findings suggest that a signalling cascade involving sequential activation of NF‐κB/p65 and Par‐4 may participate in relatively early events of endometrial tumourigenesis, leading to modulation of cell kinetics including apoptosis and cell cycle progression. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Plasmin induces apoptosis of aortic valvular myofibroblasts
Authors: Kochtebane Najlah , Choqueux Christine , Passefort Stéphanie , Nataf Patrick , Messika‐Zeitoun David , Bartagi Aghleb , Michel Jean‐Baptiste , Anglés‐Cano Eduardo , Jacob Marie‐Paule 
Published: December 2009

AbstractPrevious studies have described remodelling of the extracellular substratum by matrix metalloproteinases (MMPs) in aortic valves. However, involvement of the fibrinolytic system has not yet been analysed. We hypothesized that plasminogen and plasminogen activator(s) are present in aortic valves and that plasminogen activation could induce the degradation of adhesive proteins and apoptosis of the valvular myofibroblasts. We employed ELISA, western blotting, fibrin‐agar zymography, and immunochemistry to detect components of the plasminogen activation system, in samples of aortic valves and valvular myofibroblasts in primary culture. Using myofibroblast cultures, real‐time measurement of plasminogen activation was performed in the absence and presence of inhibitors (amiloride, ε‐aminocaproic acid, and an MMP inhibitor); the degradation of fibronectin was visualized on western blots; and the apoptotic process was assessed by detection of phosphatidylserine exposure (binding of FITC‐annexin V) and DNA fragmentation (TUNEL and ELISA). We demonstrate that a time‐ and plasminogen concentration‐dependent generation of plasmin occurs on the surface of cultured valvular myofibroblasts expressing both u‐PA and t‐PA. Only u‐PA appears to activate plasminogen as t‐PA is essentially found in complex with PAI‐1. Plasmin‐dependent degradation of pericellular proteins, such as fibronectin, leads to cell detachment and apoptosis. In conclusion, various proteins of the fibrinolytic system are synthesized in vitro by cultured myofibroblasts from aortic valves, leading to plasmin‐dependent cell detachment‐induced apoptosis, a biological process named anoikis. The presence of plasminogen in aortic valves suggests that this process may be operating in vivo and may participate in valvular tissue remodelling, as also suggested by the finding of apoptotic cells in valvular tissue. This is the first demonstration of the presence and potential role of enzymes of the fibrinolytic system in aortic valves. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Intraoperative examination (IOE) in pediatric extracranial tumors
Authors: Dall'Igna Patrizia , d'Amore Emanuele S.G. , Cecchetto Giovanni , Bisogno Gianni , Carretto Elena , Bitetti Stefania , Famengo Barbara , Alaggio Rita 
Published: January 2010

AbstractBackground and objectivesIntraoperative evaluation of surgical specimens by frozen sections (IOE) is required to distinguish benign and malignant lesions, assess surgical margins, and determine sample adequacy of biopsies. In the last years, it has been used also for therapeutic decisions, particularly in children, who may need other ancillary procedures, in case of malignancies. Our purpose was the evaluation of diagnostic accuracy, limits, and different role of IOE in pediatric pathology.Patients and methodsFrom 1990 to 2001, 416 IOEs were performed in 341 children, affected by lymph node pathology, soft tissue tumors, neuroblastic tumors, gonadal germ cell, and stromal tumors, hepatic lesions, renal tumors, and others; the technique was also used to assess surgical margins during major surgeries. IOEs were obtained from Tru‐cut biopsies (<1 cm3), wide biopsies (>1 cm3), or from the whole lesions, and the subsequent final diagnoses were classified as concordant, discordant, and deferred.ResultsThree hundred seventy cases (88.9%) were concordant, 10 (2.4%) discordant, and 36 (8.6%) deferred. The disagreement was found in two small lymph node samples, three soft tissue tumors, one hepatoblastoma, one metastasis, and three surgical margins. The deferred diagnoses were related to lymph node and soft tissue lesions.ConclusionsIOE in pediatric oncology may integrate the diagnostic process and supports the therapeutic guidelines of different tumors. In our study, the diagnostic concordance was satisfactory. A rational use of the technique and the awareness of its limits are, however, prerequisites to avoid the risk of overtreatment. Pediatr Blood Cancer 2010;54:388–393. © 2010 Wiley‐Liss, Inc.
High pressure torsion of binary Cu64.5Zr35.5 alloy
Authors: Révész Ádám , Kovács Zsolt , Szabó Péter J. , Schafler Erhard , Varga Lajos K. , Hóbor Sándor 
Published: January 2010

AbstractDisks of Cu64.5Zr35.5 composition were deformed by high pressure torsion. The cross‐section and radial dependence of the microstructure was monitored by X‐ray diffraction and scanning electron microscopy. The extreme shear deformation, particularly at the perimeter of the disk promotes the formation of a homogeneous surface layer with a thickness of 10 µm and the blocks of Cu‐enriched regions in the bulk. Calorimetric measurements indicate the presence of a minor amorphous component.
State, forest and community: challenges of democratically decentralizing forest management in the Centre‐West Region of Burkina Faso
Authors: Bouda Henri‐Noël , Savadogo Patrice , Tiveau Daniel , Ouedraogo Boureima 
Published: December 2009

AbstractThis study examines challenges associated with early stages of decentralizing the administration and management of forest resources in the Centre‐West Region of Burkina Faso. It is based on fieldwork using rapid rural appraisal, focus group discussions and interviews with key stakeholders, methodology to explore the strengths and weaknesses of participatory forest management, and the main issues and challenges involved in these processes. The study found that a shift of administrative authority to the local level will not guarantee transparency and good governance in the forest sector unless measures are taken to remove challenging obstacles. The central government is still reluctant to decentralize a revenue‐generating sector such as forestry and the involvement of civil society remains weak. Decentralization also results in a plethora of conflicts at the local level as new responsibilities and opportunities arise with the devolution of new powers to the community. Decentralization of forest management will probably remain a work in progress for the foreseeable future. Thus, we recommend the introduction or reinforcement of participatory development programs through local dialogue with various stakeholders and an investigation of new policy and institutional arrangements that may promote equitable forest management. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.
Model‐based code generation for HLA federates
Authors: Adak Mehmet , Topçu Okan , Oguztüzün Halit 
Published: December 2009

AbstractThis paper addresses the problem of automated code generation for a High Level Architecture compliant federate application given its behavior model. The behavior model is a part of the architectural model of a federation that the federate can participate in. The federate behavior model is based on Live Sequence Charts, adopted as the behavioral specification formalism in the Federation Architecture Metamodel (FAMM). FAMM serves as a formal language for describing federation architectures. An objective is to help the testing of federation architecture by means of its prototype implementation early in the development lifecycle. A further objective is to help developers construct complete federate applications that are well modularized. The approach to achieve these objectives is aspect‐oriented in that the generated code, which handles the federate's interactions with a federation execution, serves as the base code, where the computation logic is to be weaved as an aspect. Copyright © 2009 John Wiley & Sons, Ltd.
Camila, the earth, and the sun: Constructing an idea as shared intellectual property
Authors: Radinsky Josh , Oliva Sonia , Alamar Kimberly 
Published: January 2010

AbstractRecent research has challenged traditional assumptions that scientific practice and knowledge are essentially individual accomplishments, highlighting instead the social nature of scientific practices, and the co‐construction of scientific knowledge. Similarly, new research paradigms for studying learning go beyond focusing on what is “in the head” of individual students, to study collective practices, distributed cognition, and emergent understandings of groups. These developments require new tools for assessing what it means to learn to “think like a scientist.” Toward this goal, the present case study analyzes the discourse of a 6th‐grade class discussing one student's explanation for seasonal variations in daylight hours. The analysis identifies discourse moves that map to disciplinary practices of the social construction of science knowledge, including (1) beginning an explanation by reviewing the community's shared assumptions; (2) referencing peers' work as warrants for an argument; and (3) building from isolated ideas, attributed to individuals, toward a coherent situation model, attributed to the community. The study then identifies discourse moves through which the proposed explanation was taken up and developed by the group, including (4) using multiple shared representations; (5) leveraging peers' language to clarify ideas; and (6) negotiating language and representations for new, shared explanations. Implications of this case for rethinking instruction, assessment, and classroom research are explored. © 2009 Wiley Periodicals, Inc. J Res Sci Teach 47:619–642, 2010
Boosting
Authors: Bühlmann Peter , Yu Bin 
Published: December 2009

AbstractIn this contribution, we review boosting, one of the most effective machine learning methods for classification and regression. Most of the article takes the gradient descent point of view, even though we do include the margin point of view as well. In particular, AdaBoost in classification and various versions of L2boosting in regression are covered. Advice on how to choose base (weak) learners and loss functions and pointers to software are also given for practitioners. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:Statistical Learning and Exploratory Methods of the Data Sciences > Classification and Regression Trees (CART)
Importance sampling: a review
Authors: Tokdar Surya T. , Kass Robert E. 
Published: December 2009

AbstractWe provide a short overview of importance sampling—a popular sampling tool used for Monte Carlo computing. We discuss its mathematical foundation and properties that determine its accuracy in Monte Carlo approximations. We review the fundamental developments in designing efficient importance sampling (IS) for practical use. This includes parametric approximation with optimization‐based adaptation, sequential sampling with dynamic adaptation through resampling and population‐based approaches that make use of Markov chain sampling. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:Statistical and Graphical Methods of Data Analysis > Sampling
Histogram
Authors: Scott David W. 
Published: December 2009

AbstractHistogram is one of the most important graphical objects in statistical practice. In addition, the histogram provides a consistent estimate of any density function with very few assumptions. Construction of a density histogram with arbitrary mesh is described. Asymptotic theory of optimal histograms is used to provide practical rules for choosing a bin width with real data. Cross‐validation is shown to provide useful estimates of both the bin width and the bin origin. Examples are displayed using data from Sammy Sosa's best year for hitting home runs. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:Statistical and Graphical Methods of Data Analysis > Density Estimation
Minimum covariance determinant
Authors: Hubert Mia , Debruyne Michiel 
Published: December 2009

AbstractThe minimum covariance determinant (MCD) estimator is a highly robust estimator of multivariate location and scatter. It can be computed efficiently with the FAST‐MCD algorithm of Rousseeuw and Van Driessen. Since estimating the covariance matrix is the cornerstone of many multivariate statistical methods, the MCD has also been used to develop robust and computationally efficient multivariate techniques.In this paper, we review the MCD estimator, along with its main properties such as affine equivariance, breakdown value, and influence function. We discuss its computation, and list applications and extensions of the MCD in theoretical and applied multivariate statistics. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Robust Methods
Randomized clinical trials
Authors: Zheng Lu , Zelen Marvin 
Published: December 2009

AbstractRandomization is widely recognized as a fundamental principle in the design of Phase III clinical trials. It is a way to minimize conscious and unconscious bias among patients and physicians with regard to treatment assignment and treatment acceptability. This paper outlines the advantages and disadvantages of randomization in clinical trials with discussions in permuted blocks, stratified randomization, cluster randomization, and the role of randomization as a basis for inference. Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under:

Applications of Computational Statistics > Clinical Trials