bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data‐dependent electron transfer dissociation of large peptides and medium size proteins in a QTOF instrument on a liquid chromatography timescale
Authors: Hartmer Ralf G. , Kaplan Desmond A. , Stoermer Carsten , Lubeck Markus , Park Melvin A. 
Published: July 2009

AbstractLiquid chromatography (LC) electron transfer dissociation (ETD) tandem mass spectrometry (MS/MS) of protein digests is demonstrated in a hybrid quadrupole‐hexapole orthogonal time‐of‐flight (OTOF) mass spectrometer. Analyte ions are selected in a mass‐analyzing quadrupole, accumulated in the hexapole linear ETD reaction cell and mutually stored with ETD reagent anions. Product ions are collected in an ion cooler and then analyzed by an OTOF mass analyzer. The hexapole structure of the ETD reaction cell allows for a broad fragment ion mass range distribution and a high ion storage capacity. Analytically useful ETD OTOF‐MS/MS spectra could be obtained at a rate of faster than 2 Hz. When used in conjunction with LC this high speed allows for several MS and MS/MS spectra to be obtained across each LC peak. An MS scan is used to select the precursor ions. With a 1 m flight tube and single reflection, resolutions of about 10 k and a mass accuracy of 5 ppm were achieved. When analyzing a 100 fmol solution of a tryptic digest of bovine serum albumin (BSA) by LC/ETD MS/MS, 27 unique peptides were identified with a summed Mascot score of 1316 using the Swiss Prot database. In addition, we explored the capability for analyzing small proteins with the present hybrid instrument. ETD MS/MS of intact ubiquitin ([M+12H]12+) leads to the identification of the protein with a Mascot score of 264. Copyright © 2009 John Wiley & Sons, Ltd.
Intention to treat, per protocol, as treated and instrumental variable estimators given non‐compliance and effect heterogeneity
Authors: McNamee Roseanne 
Published: July 2009

AbstractWe consider the behaviour of three approaches to efficacy estimation—using so‐called ‘as treated’ (AT), ‘per protocol’ (PP) and ‘instrumental variable’ (IV) analyses—and of the Intention to Treat estimator, in a two‐arm randomized treatment trial with a Normally distributed outcome when there is treatment effect heterogeneity and non‐random compliance with assigned treatment. Formulae are derived for the bias of estimators when used either to estimate average treatment effect (ACE) or to estimate complier average treatment effect (CACE) under several models for the relationship between compliance and potential outcomes. These enable the expected values of AT, PP and IV estimators to be ranked in relation to ACE, and show that AT and PP estimators are generally biased for both ACE and CACE even under homogeneity. However, we show that the difference between any pair of (AT, PP, IV) estimates can be used to estimate the correlation between the latent variable determining compliance behaviour and one potential outcome. In the absence of measures that predict compliance, bounds for ACE can only be set given strong assumptions. Regarding the Intention to Treat estimator, while this is ‘biased towards the null’ if viewed as a measure of CACE, we show that it is not always so in relation to ACE. Finally we discuss the behaviour of the estimators under weak and strong null hypotheses. Copyright © 2009 John Wiley & Sons, Ltd.
Developing multicomponent interventions using fractional factorial designs
Authors: Chakraborty Bibhas , Collins Linda M. , Strecher Victor J. , Murphy Susan A. 
Published: July 2009

AbstractMulticomponent interventions composed of behavioral, delivery, or implementation factors in addition to medications are becoming increasingly common in health sciences. A natural experimental approach to developing and refining such multicomponent interventions is to start with a large number of potential components and screen out the least active ones. Factorial designs can be used efficiently in this endeavor. We address common criticisms and misconceptions regarding the use of factorial designs in these screening studies. We also provide an operationalization of screening studies. As an example, we consider the use of a screening study in the development of a multicomponent smoking cessation intervention. Simulation results are provided to support the discussions. Copyright © 2009 John Wiley & Sons, Ltd.
Two‐stage design of clinical trials involving recurrent events
Authors: Cook Richard J. , Bergeron Pierre‐Jerome , Boher Jean‐Marie , Liu Yang 
Published: July 2009

AbstractMixed Poisson models are often used for the design of clinical trials involving recurrent events since they provide measures of treatment effect based on rate and mean functions and accommodate between individual heterogeneity in event rates. Planning studies based on these models can be challenging when there is a little information available on the population event rates, or the extent of heterogeneity characterized by the variance of individual‐specific random effects. We consider methods for adaptive two‐stage clinical trial design, which enable investigators to revise sample size estimates using data collected during the first phase of the study. We describe blinded procedures in which the group membership and treatment received by each individual are not revealed at the interim analysis stage, and a ‘partially blinded’ procedure in which group membership is revealed but not the treatment received by the groups. An EM algorithm is proposed for the interim analyses in both cases, and the performance is investigated through simulation. The work is motivated by the design of a study involving patients with immune thrombocytopenic purpura where the aim is to reduce bleeding episodes and an illustrative application is given using data from a cardiovascular trial. Copyright © 2009 John Wiley & Sons, Ltd.
Designs for dose–escalation trials with quantitative responses
Authors: Bailey R. A. 
Published: July 2009

AbstractIn a dose–escalation trial for a new drug, each successive dose is tested on a new cohort of volunteer subjects, so that if any dose produces severe adverse reactions then higher doses are not tested. However, if there are other differences between the cohorts, such as differences in environmental health factors, type of person or experimental procedure, then these differences may obscure the differences between doses. Therefore, cohorts should be fitted in the analysis, as either fixed or random effects. I suggest that, if this is done, then there are three simple principles that reduce variance (i) allocating no more than half the subjects in any cohort to any single dose; (ii) subject to safety constraints, using as many different doses as possible in each cohort; (iii) using one more cohort than the number of doses, without increasing the total number of subjects. Using these principles, I propose some new designs that conform to the safety rules of traditional dose–escalation trials while reducing the variance of the estimators of differences between the doses by a factor of two or more, for the same number of subjects. Copyright © 2009 John Wiley & Sons, Ltd.
Mature Adult Dystrophic Mouse Muscle Environment Does Not Impede Efficient Engrafted Satellite Cell Regeneration and Self-Renewal
Authors: Boldrin Luisa , Zammit Peter Steven , Muntoni Francesco , Morgan Jennifer Elizabeth 
Published: July 2009

Abstract
Changes that occur in the skeletal muscle environment with the progress of muscular dystrophies may affect stem cell function and result in impaired muscle regeneration. It has previously been suggested that the success of stem cell transplantation could therefore be dependent both on the properties of the cell itself and on the host muscle environment. Here we engrafted young and mature adult mdx-nude mice, which are the genetic homolog of Duchenne muscular dystrophy, with a small number of satellite cells freshly isolated from young, normal donor mice. We found that the donor satellite cells contributed to muscle regeneration and self-renewal as efficiently within mature adult, as in young, dystrophic host muscle. Donor-derived satellite cells also contributed to robust regeneration after further injury, showing that they were functional despite the more advanced dystrophic muscle environment. These findings provide evidence that muscle tissue in a later stage of dystrophy may be effectively treated by stem cells.
Review of knowledge development for the design of offshore wind energy technology
Authors: Zaaijer M.B. 
Published: July 2009

AbstractOffshore wind energy (OWE) is one of the emerging sustainable energy sources that are currently developed under public support. In the long run, it needs to become competitive in the energy market under the same conditions as regular sources, and it is expected that engineering design can contribute significantly towards this goal. Various activities, both academic and industrial, have contributed to the knowledge base that is needed for design and technology development and the paper reviews this knowledge. The objectives of the paper are to identify points of attention for future research and to suggest directions where academic research can contribute to design improvements. The review and the suggestions do not address very specific areas of the broad range of knowledge, but rather characterizes the types of knowledge that are available and which are missing. Many research activities contribute to foundational knowledge, needed to perform simulation and analysis of provisional design solutions. Most of the design‐related studies reviewed for this paper are solution oriented and contribute to contextualized knowledge. Studies that put more emphasis on methodologies largely target optimization methods. Existing knowledge appears to be weak in methodological support of the integration of the various asynchronous design processes that contribute to OWE development. The paper leads to a plea to generate such knowledge, which can be transferred from academia to industry to enhance the design strength already present in the industry. Several points of attention are given for this type of research. Copyright © 2009 John Wiley & Sons, Ltd.
Selection of cell death‐deficient p53 mutants in Saccharomyces cerevisiae
Authors: Yacoubi‐Hadj Amor Ines , Smaoui Kamel , Belguith Hanène , Djemal Lamia , Dardouri Mosbeh , Mokdad‐Gargouri Raja , Gargouri Ali 
Published: July 2009

AbstractThe budding yeast Saccharomyces cerevisiae is a useful system for the detection and transcriptional evaluation of mutant p53 in cancer. In previous work we showed that the overexpression of wild‐type p53 induces yeast cell death on minimal medium; however, the R248W p53 mutant was completely inactive, and we suggested that ROS production is a key event in p53‐induced yeast cell death. In this study we explored the effect of other p53 mutants, such as the hot‐spot mutant R282W and the double mutant N268S::I332V. Unexpectedly, both mutants behaved inversely to R248W, as they completely inhibited yeast growth on minimal medium and induced ROS production. This phenotype ‘yeast cell death on minimal medium’ allowed for the subsequent screening of intragenic p53‐inactivating mutations. In all cases, the ‘revertant yeast clones’ display a complete p53 inactivation through either gross deletion or nonsense mutations. More interestingly, missense mutations were also found: the deletion of I255 or substitution of R337G completely inactivated the p53 mutant R282W in the yeast context. Taken together, these results suggest that p53 tumour‐derived mutants could be classified according to their ability to induce yeast cell death and not uniquely by their transcriptional activity on a selected target reporter gene. Copyright © 2009 John Wiley & Sons, Ltd.
Fed‐batch methanol feeding strategy for recombinant protein production by Pichia pastoris in the presence of co‐substrate sorbitol
Authors: Çelik Eda , Çalık Pınar , Oliver Stephen G. 
Published: July 2009

AbstractBatch‐wise sorbitol addition as a co‐substrate at the induction phase of methanol fed‐batch fermentation by Pichia pastoris (Mut+) was proposed as a beneficial recombinant protein production strategy and the metabolic responses to methanol feeding rate in the presence of sorbitol was systematically investigated. Adding sorbitol batch‐wise to the medium provided the following advantages over growth on methanol alone: (a) eliminating the long lag‐phase for the cells and reaching ‘high cell density production’ at t = 24 h of the process (CX = 70 g CDW/l); (b) achieving 1.8‐fold higher recombinant human erythropoietin (rHuEPO) (at t = 18 h); (c) reducing specific protease production 1.2‐fold; (d) eliminating the lactic acid build‐up period; (e) lowering the oxygen uptake rate two‐fold; and (f) obtaining 1.4‐fold higher overall yield coefficients. The maximum specific alcohol oxidase activity was not affected in the presence of sorbitol, and it was observed that sorbitol and methanol were utilized simultaneously. Thus, in the presence of sorbitol, 130 mg/l rHuEPO was produced at t = 24 h, compared to 80 mg/l rHuEPO (t = 24 h) on methanol alone. This work demonstrates not only the ease and efficiency of incorporating sorbitol to fermentations by Mut+ strains of P. pastoris for the production of any bio‐product, but also provides new insights into the metabolism of the methylotrophic yeast P. pastoris. Copyright © 2009 John Wiley & Sons, Ltd.
Two‐Dimensional and Three‐Dimensional Lanthanide Coordination Polymers Built from 4‐Hydroxypyridine‐2,6‐dicarboxylic Acid Ligand
Authors: Sun Ya‐Guang , Rong Shu‐Ting , Yu Wan , Wu Yong‐Li , Ding Fu , Gao En‐Jun , Zhang Wan‐Zhong , Verpoort Francis 
Published: July 2009

Abstract4‐Hydroxypyridine‐2,6‐dicarboxylic acid (H3CAM) reacts with Ln2O3(Ln = La, Ce) or Ln(NO3)3 (Ln = Sm, Dy, Gd, Ho) in hydrothermal reactions to form a series of lanthanide coordination polymers 1–6. Elemental analysis, IR spectra and X‐ray crystal structure analysis were carried out to determine the composition and crystal structure of 1–6. Compounds 1 and 2 are isostructural and contain tetranuclear metallic ring unit and 3D framework. 4–6 are isostructural contain 2D network. Furthermore, the photoluminescent properties of 3 and 4 at room temperature were also studied.
Steady two‐dimensional periodic motion of a micropolar fluid near an infinite array of moving walls
Authors: Lok Y.Y. , Pop I. , Ingham D.B. 
Published: July 2009

AbstractAn analysis of the steady two‐dimensional flow of a micropolar fluid that is generated by a moving wall has been performed in this paper. The wall is assumed to move with a sinusoidal velocity in the direction that is parallel to the wall. Two‐term analytical and numerical solutions are obtained for several values of the Reynolds number Re and the micropolar parameter K. Both the cases of strong and weak concentration of micropolar fluids are considered. It is found that the maximum value of the stream function and microrotation increase as K increases. However, the fluid velocity decreases as K increases. It is observed that the streamlines are in the form of a row of clockwise rotating cells which are located close to the wall. For large value of Re, it is found that a recirculation in the vorticity and a drag in the microrotation appear near to the wall at y = 0.
A numerical study for linear isotropic Cosserat elasticity with conformally invariant curvature
Authors: Jeong J. , Ramézani H. , Münch I. , Neff P. 
Published: July 2009

AbstractWe investigate the numerical response of the linear Cosserat model with conformal curvature. In our simulations we compare the standard Cosserat model with a novel conformal Cosserat model in torsion and highlight its intriguing features. In all cases, free boundary conditions for the microrotations overline A are applied. The size‐effect response is markedly changed for the novel curvature expression. Our results suggest that the Cosserat couple modulus µc > 0 remains a true material parameter independent of the sample size which is impossible for stronger, pointwise positive curvature expressions.
Crack identification by multifractal analysis of a dynamic rotor response
Authors: Litak G. , Sawicki J.T. 
Published: July 2009

AbstractMultifractal analysis has been used to diagnose cracked and healthy rotors. Is has been shown that the complexity and regularity criteria of the dynamical systems defined by the multiple scaling of the time series can indicate the damages of the rotating shaft. Relation to the standard power spectrum technique has been also discussed.
Reasoning with graph constraints
Authors: Orejas Fernando , Ehrig Hartmut , Prange Ulrike 
Published: July 2009

Abstract
Graph constraints were introduced in the area of graph transformation, in connection with the notion of (negative) application conditions, as a form to limit the applicability of transformation rules. However, we believe that graph constraints may also play a significant role in the area of visual software modelling or in the specification and verification of semi-structured documents or websites (i.e. HTML or XML sets of documents). In this sense, after some discussion on these application areas, we concentrate on the problem of how to prove the consistency of specifications based on this kind of constraints. In particular, we present proof rules for two classes of graph constraints and show that our proof rules are sound and (refutationally) complete for each class. In addition, we study clause subsumption in this context as a form to speed up refutation.
Optimization of an Oil Extraction Process for Algae from the Treatment of Manure Effluent
Authors: Mulbry Walter , Kondrad Shannon , Buyer Jeffrey , Luthria Devanand L. 
Published: July 2009

AbstractIncreasing interest in the coupling of biological wastewater treatment processes with the generation of value‐added products (such as oil containing ω‐3 fatty acids (FA)) has stimulated efforts in adapting extraction methods for treatment byproducts. This study’s objective was to compare a high temperature/pressure extraction method (accelerated solvent extraction) (ASE) and a manual extraction method (modified Folch extraction) with regard to their ability to extract total oil from three algae samples from the treatment of dairy manure effluent. The efficiency of total oil and FA extraction with three solvents (chloroform/methanol, isopropanol/hexane, and hexane) was also evaluated using the ASE method. Results showed that the ASE method yielded higher values for total oil content compared to the Folch method but similar values for FA content and composition after four extraction cycles with chloroform/methanol. However, the ASE method yielded much higher amounts of FA in the first cycle (85–95% of total extracted) compared to the Folch method (44–55% of total extracted in the first cycle). As expected, the extraction efficiency of the ASE method for FA was dependent on the extraction solvent. FA content values using ASE with chloroform/methanol > isopropanol/hexane > hexane. FA content values using the Folch method or ASE with chloroform/methanol were not significantly influenced by sample particle size within the size range of 0.1–1 mm.
Low frequency electromagnetic radiation and hearing
Authors: Morales J , Garcia M , Perez C , Valverde J V , Lopez-Sanchez C , Garcia-Martinez V , Quesada J L 
Published: July 2009

AbstractObjective:To analyse the possible impact of low and extremely low frequency electromagnetic fields on the outer hairs cells of the organ of Corti, in a guinea pig model.Materials and methods:Electromagnetic fields of 50, 500, 1000, 2000, 4000 and 5000 Hz frequencies and 1.5 µT intensity were generated using a transverse electromagnetic wave guide. Guinea pigs of both sexes, weighing 100–150 g, were used, with no abnormalities on general and otic examination. Total exposure times were: 360 hours for 50, 500 and 1000 Hz; 3300 hours for 2000 Hz; 4820 hours for 4000 Hz; and 6420 hours for 5000 Hz. One control animal was used in each frequency group. The parameters measured by electric response audiometer included: hearing level; waves I–IV latencies; wave I–III interpeak latency; and percentage appearance of waves I–III at 90 and 50 dB sound pressure level intensity.Results:Values for the above parameters did not differ significantly, comparing the control animal and the rest of each group. In addition, no significant differences were found between our findings and those of previous studies of normal guinea pigs.Conclusion:Prolonged exposure to electromagnetic fields of 50 Hz to 5 KHz frequencies and 1.5 µT intensity, produced no functional or morphological alteration in the outer hair cells of the guinea pig organ of Corti.
Crux et Vocatio
Authors: Jorgenson Allen 
Published: July 2009

AbstractThis article examines Luther's theology of the cross in relation to his treatment of vocation and explores the contemporary utility of both. It is argued that theologians who reduce Luther's theology of the cross to an existential descriptor fail on two accounts. First, they do not comprehend the manner in which a theology of the cross does not describe anxiety but rather induces it so as to create theologians of the cross out of theologians of glory. Second, a reduction of a theology of the cross to an existential descriptor fails to apprehend the public significance of the same insofar as a theology of the cross is intimately related to Luther's treatment of vocation and its concomitant explication of the two reigns of God. Luther's treatment of vocation points to the manner in which the Christian is shaped by the cross in the give and take of human community. This is not to gainsay certain deficiencies in Luther's treatment of vocation. Chief among these are Luther's tendency to restrict language of vocation to individuals and his insistence on vocational intransigence. A contemporary engagement of the cross and vocation entails both a critical analysis of the manner in which the private has now eclipsed the public and an attempt to move beyond Luther by way of Luther in underscoring the gift of ecclesial vocation.
Jonathan Edwards and the lapsarian debate
Authors: Allen Michael 
Published: July 2009

AbstractContrary to what might be expected from such a thinker, Jonathan Edwards was restrained in conversation with the Reformed debate about the order of the divine decrees, known as the infralapsarian/supralapsarian debate. I will address Edwards's caution regarding this particular debate: first, by tracing the contours of the broader Reformed debate on the divine decrees and its evolution from engagement of Arminian theology to that of theodicy; second, by noting where Edwards does not speak to this debate and exegeting the few passages where he does take it up; third, by analysing the particular questions that Edwards addresses when he does engage the debate; fourth, by pointing to constructive lessons gained by understanding why a careful thinker might be atypically silent. I will demonstrate that Edwards engaged the lapsarian debate insofar as was necessary to rebuke the Arminian denial of unconditional election, yet he refused to engage the debate as a means of articulating a theodicy. In both his engagement and disengagement, Edwards refused to answer the debate on its standard terms and offers an example of carefully crafting doctrine according to theological and contextual concerns.