bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time‐of‐flight and LTQ‐Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro – amitriptyline and verapamil as model compounds
Authors: Rousu Timo , Herttuainen Jukka , Tolonen Ari 
Published: March 2010

AbstractLiquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time‐ and cost‐effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early‐phase ‘one lab visit only’ approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time‐of‐flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ‐Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q‐Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high‐important accurate mass data, they suffered from many false negatives, and especially with the QqQ, from very high overall time consumption. Copyright © 2010 John Wiley & Sons, Ltd.
The natural abundance of 15N in plant and soil‐available N indicates a shift of main plant N resources to NO from NH along the N leaching gradient
Authors: Takebayashi Yu , Koba Keisuke , Sasaki Yuji , Fang Yunting , Yoh Muneoki 
Published: March 2010

AbstractTo investigate which of ammonium (NH) or nitrate (NO) is used by plants at gradient sites with different nitrogen (N) availability, we measured the natural abundance of 15N in foliage and soil extractable N. Hinoki cypress (Chamaecyparis obtusa Endlicher) planted broadly in Japan was selected for use in this study. We estimated the source proportion of foliar N (NH vs. NO) quantitatively using mass balance equations. The results showed that C. obtusa used mainly NH in N‐limited forests, although the dependence of C. obtusa on NO was greater in other NO‐rich forests. We regarded dissolved organic N (DON) as a potential N source because a previous study demonstrated that C. obtusa can take up glycine. Thus we added DON to our mass balance equations and calculated the source proportion using an isotope‐mixing model (IsoSource model). The results still showed a positive correlation between the calculated plant N proportion of NO and the NO pool size in the soil, indicating that high NO availability increases the reliance of C. obtusa on NO. Our data suggest the shift of the N source for C. obtusa from NH to NO according to the relative availability of NO. They also show the potential of the foliar δ15N of C. obtusa as an indicator of the N status in forest ecosystems with the help of the δ15N values of soil inorganic and organic N. Copyright © 2010 John Wiley & Sons, Ltd.
Mapping site‐specific protein N‐glycosylations through liquid chromatography/mass spectrometry and targeted tandem mass spectrometry
Authors: Wu Yin , Mechref Yehia , Klouckova Iveta , Mayampurath Anoop , Novotny Milos V. , Tang Haixu 
Published: March 2010

AbstractGlycosylation is one of the most common posttranslational modifications (PTMs) of proteins, the characterization of which is commonly achieved through proteomic protocol, involving trypsin digestion followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). However, it is often not possible to characterize all glycopeptides in a complex sample because of the high complexity of glycoproteomic samples, and the relative lower abundances of glycopeptides in comparison to the unmodified peptides. We present here a targeted MS/MS analysis approach, which utilizes a previously developed computational tool, GlyPID, to guide multiple experiments, thus permitting a complete characterization of all N‐glycosylation sites of glycoproteins present in a complex sample. We have tested our approach using model glycoproteins analyzed by high‐resolution LTQ‐FT MS. The results demonstrate a potential use of our method for a high‐throughput characterization of complex mixtures of glycosylated proteins. Copyright © 2010 John Wiley & Sons, Ltd.
Formation of unexpected ions from a first‐generation polyamidoamine dendrimer by use of methanol: an artefact due to electrospray emitter corrosion?
Authors: Maire Florian , Lange Catherine M. 
Published: March 2010

AbstractWe report the formation of unexpected ions during the analyses of a first‐generation polyamidoamine dendrimer in negative ion mode using an ion trap equipped with an electrospray ionisation source. These surprising ions corresponded to an increase of 12 m/z units over those expected. The formation of the unexpected ions was dependent on the tuning of the solution flow rate and the capillary high voltage. In addition, measurements of unusual value of the current suggested that a reaction was occurring in the corona plasma. The influence of methanol in this phenomenon was demonstrated by using CD3OH in the sample preparation. We propose two structures to explain the observed adduct based on the results of MS2 experiments and by referring to previous work dealing with 12 m/z units addition. We showed that a corona discharge caused by alterations taking place to the electrospray capillary emitter was the origin of these unexpected ions. Finally, we discuss the mechanism involved in the formation of the ions and we propose means to control such artefacts. Copyright © 2010 John Wiley & Sons, Ltd.
Data‐independent liquid chromatography/mass spectrometry (LC/MSE) detection and quantification of the secreted Apium graveolens pathogen defense protein mannitol dehydrogenase
Authors: Blackburn Kevin , Cheng Fang‐yi , Williamson John D. , Goshe Michael B. 
Published: March 2010

AbstractPlant cells secrete a wide variety of defense‐related proteins into the extracellular space or apoplast in response to pathogen attack. One of these, mannitol dehydrogenase (MTD), is normally a cytoplasmic enzyme whose primary role is the regulation of intracellular levels of the sugar alcohol mannitol in plants. Recent immunological and biochemical evidence, however, suggests that MTD is also secreted into the apoplast in response to pathogen attack, despite lacking a known peptide signal sequence for Golgi‐mediated secretion. Because many plant pathogenic fungi secrete mannitol to overcome pathogen‐induced generation of reactive oxygen species (ROS) by the plant, extracellular localization of MTD is hypothesized to have a defensive role of catabolizing pathogen‐secreted mannitol. In the current study, LC/MSE was used to analyze proteins in the secretome of Apium graveolens (celery) following treatment with salicylic acid (SA), an endogenous elicitor of defense responses in plants. Levels of MTD in the secretome of SA‐treated celery cell cultures were found to be induced at least 18‐fold over secretome samples from cell cultures not exposed to SA. This value is in close agreement with published immunological and biochemical observations. Overall, this report provides the first mass spectrometry identification and quantification measurements supporting the hypothesis that MTD is secreted in response to simulated pathogen attack via a non‐classical secretion mechanism. As demonstrated with MTD secretion, LC/MSE can be implemented as a discovery‐driven MRM‐based quantitative approach which can be used to reveal potential post‐translational modifications, thus providing a new method in the area of gel‐free and label‐free proteomic analysis. Copyright © 2010 John Wiley & Sons, Ltd.
Elucidation of the dissociation pathways of electro‐ionized estrone
Authors: Bouchonnet Stéphane , Genty Christophe , Bourcier Sophie , Sablier Michel 
Published: March 2010

AbstractWith the future aim of using gas chromatography coupled with mass spectrometry to characterize the transformation products of estrone submitted to UV‐photolysis or to waste water treatment plants, an interpretation of the electron impact mass spectrum of estrone is presented. Fragmentation mechanisms are proposed on the basis of high‐resolution measurements performed with a magnetic sector analyzer. Multiple‐stage mass spectrometry experiments were carried out using an ion trap mass spectrometer. The structures proposed for product ions were confirmed by the m/z shifts observed in the estrone‐d4 and estrone methyl ether electron ionization mass spectra. If the formation of some of the most abundant ions may easily be explained by α‐cleavages and retro‐Diels‐Alder type rearrangements, complex mechanisms need to be considered to rationalize the formation of others. Isotope labelling allows discrimination of isobaric ions. Copyright © 2010 John Wiley & Sons, Ltd.
Application of thin‐layer chromatography/infrared matrix‐assisted laser desorption/ionization orthogonal time‐of‐flight mass spectrometry to structural analysis of bacteria‐binding glycosphingolipids selected by affinity detection
Authors: Müsken Anne , Souady Jamal , Dreisewerd Klaus , Zhang Wenlan , Distler Ute , Peter‐Katalinić Jasna , Miller‐Podraza Halina , Karch Helge , Müthing Johannes 
Published: March 2010

AbstractGlycosphingolipids (GSLs) play key roles in the manifestation of infectious diseases as attachment sites for pathogens. The thin‐layer chromatography (TLC) overlay assay represents one of the most powerful approaches for the detection of GSL receptors of microorganisms. Here we report on the direct structural characterization of microbial GSL receptors by employment of the TLC overlay assay combined with infrared matrix‐assisted laser desorption/ionization orthogonal time‐of‐flight mass spectrometry (IR‐MALDI‐o‐TOF‐MS). The procedure includes TLC separation of GSL mixtures, overlay of the chromatogram with GSL‐specific bacteria, detection of bound microbes with primary antibodies against bacterial surface proteins and appropriate alkaline phosphatase labeled secondary antibodies, and in situ MS analysis of bacteria‐specific GSL receptors. The combined method works on microgram scale of GSL mixtures and is advantageous in that it omits laborious and time‐consuming GSL extraction from the silica gel layer. This technique was successfully applied to the compositional analysis of globo‐series neutral GSLs recognized by P‐fimbriated Escherichia coli bacteria, which were used as model microorganisms for infection of the human urinary tract. Thus, direct TLC/IR‐MALDI‐o‐TOF‐MS adds a novel facet to this fast and sensitive method offering a wide range of applications for the investigation of carbohydrate‐specific pathogens involved in human infectious diseases. Copyright © 2010 John Wiley & Sons, Ltd.
Simultaneous determination of δ15N and δ18O of N2O and δ13C of CH4 in nanomolar quantities from a single water sample
Authors: Hirota A. , Tsunogai U. , Komatsu D. D. , Nakagawa F. 
Published: March 2010

AbstractWe have developed a rapid, sensitive, and automated analytical system to simultaneously determine the concentrations and stable isotopic compositions (δ15N, δ18O, and δ13C) of nanomolar quantities of nitrous oxide (N2O) and methane (CH4) in water, by combining continuous‐flow isotope‐ratio mass spectrometry and a helium‐sparging system to extract and purify the dissolved gases. Our system, which is composed of cold traps and a capillary gas chromatograph that use ultra‐pure helium as the carrier gas, achieves complete extraction of N2O and CH4 in a water sample and separation among N2O, CH4, and the other component gases. The flow path following exit from the gas chromatograph was periodically changed to pass the gases through the combustion furnace to convert CH4 and the other hydrocarbons into CO2, or to bypass the combustion furnace for the direct introduction of eluted N2O into the mass spectrometer, for determining the stable isotopic compositions through monitoring the ions of m/z 44, 45, and 46 of CO and N2O+. The analytical system can be operated automatically with sequential software programmed on a personal computer. Analytical precisions better than 0.2‰ and 0.3‰ and better than 1.4‰ and 2.6‰ were obtained for the δ15N and δ18O of N2O, respectively, when more than 6.7 nmol and 0.2 nmol of N2O, respectively, were injected. Simultaneously, analytical precisions better than 0.07‰ and 2.1‰ were obtained for the δ13C of CH4 when more than 5.5 nmol and 0.02 nmol of CH4, respectively, were injected. In this manner, we can simultaneously determine stable isotopic compositions of a 120 mL water sample with concentrations as low as 1.7 nmol/kg for N2O and 0.2 nmol/kg for CH4. Copyright © 2010 John Wiley & Sons, Ltd.
Technology emergence through entrepreneurship across multiple industries
Authors: Woolley Jennifer 
Published: March 2010

AbstractRadical process discontinuities provide opportunities for the founding of new firms across multiple industries; however, little is known about such emergence activity. This article examines nascent technology emergence by studying patterns of related entrepreneurial activity across multiple industries based on a radical process discontinuity. Using historical and statistical methods to examine all nanotechnology firms founded before 2005, I find that during technology emergence, entrepreneurship occurs first in upstream industries. These upstream entrepreneurs provide the technological foundations that enable the founding of firms in other industries developing the technology. The results show the role of industry interaction in the development of both upstream and downstream industries. Implications for entrepreneurs and technology emergence are discussed. Copyright © 2010 Strategic Management Society.
How alliance formation shapes corporate venture capital investment in the software industry: a resource‐based perspective
Authors: Dushnitsky Gary , Lavie Dovev 
Published: March 2010

AbstractCorporate venture capital (CVC) investments serve as interfirm relationships that enable established firms to tap into emerging technology markets. Nevertheless, firms may also leverage their strategic alliances to this end. Does alliance formation reinforce or attenuate a firm's tendency to invest in entrepreneurial ventures? We introduce a resource‐based perspective whereby resource complementarity and network resource visibility prompt a reinforcing association between CVC investment and alliance formation. In turn, external resource redundancy and internal resource allocation constraints yield an attenuating effect of alliance formation on CVC investment. Analyzing the alliances and CVC investments of 372 software firms during the 1990s, we reconcile these opposing arguments by revealing an inverted U‐shaped association between CVC investment and alliance formation. Accordingly, the number of CVC investments first increases, but then decreases, with the number of alliances formed. Moreover, the positive association between CVC investment and alliance formation diminishes as firms invest in their internal resource stocks, mature, and accumulate experience with prior CVC investments. We advance strategic entrepreneurship research by elucidating the tendency of established firms to engage in CVC investment and by unpacking the complex association between different types of interfirm relationships that these firms leverage. Copyright © 2010 Strategic Management Society.
How entrepreneurs acquire the capacity to excel: insights from research on expert performance
Authors: Baron Robert A. , Henry Rebecca A. 
Published: March 2010

AbstractMost new ventures fail, but a few prosper and attain rapid growth. Many factors contribute to such outcomes, but we propose that among these are mechanisms identified by cognitive science research on the origins of expert performance. Literature on this topic indicates that across many fields (e.g., medicine, science, sports, music), outstanding performance derives largely from participation in intense, prolonged, and highly focused efforts to improve current performance—a process known as deliberate practice. By comparison, mere experience in a field and individual talent play smaller roles in generating expert performance. Additional evidence indicates that participation in deliberate practice does not simply expand domain‐specific knowledge and skills; it also generates actual enhancements to basic cognitive resources (e.g., memory, perception, metacognition). We suggest that to the extent entrepreneurs acquire enhanced cognitive resources through current or past deliberate practice, their capacity to perform tasks related to new venture success (e.g., accurate identification and evaluation of business opportunities) is enhanced and, hence, the performance of their new ventures, too, is augmented. Specific ways in which entrepreneurs can gain enhanced cognitive resources are described, and implications for entrepreneurship theory and practice are considered. Copyright © 2010 Strategic Management Society.
Foreign entry and survival in a knowledge‐intensive market: emerging economy countries' international linkages, technology competences, and firm experience
Authors: Giarratana Marco S. , Torrisi Salvatore 
Published: March 2010

AbstractThis article examines the entry into and survival in the U.S. software market by a sample of firms based in India, Ireland, and Israel, with a focus on the pre‐entry technological capabilities, international linkages, and home‐based experience of these firms as determinants. Using a novel measure of foreign activity, namely, the registration of software trademarks in the United States, this study applies the date of the first trademark application filed with the U.S. Patent and Trademark Office as a proxy for a firm's U.S. entry. Trademark renewals and new trademark applications trace the sample firms' survival. The analysis shows that international linkages have a positive relationship with entry and survival, whereas firm technological capabilities and age are not associated with entry, though technological capabilities affect the likelihood of survival. Copyright © 2010 Strategic Management Society.
A shared frailty model for case‐cohort samples: Parent and offspring relations in an adoption study
Authors: Petersen Liselotte , Sørensen Thorkild I. A. , Andersen Per Kragh 
Published: March 2010

AbstractThe Danish adoption register contains data on the 12 301 Danish nonfamilial adoptions during 1924–1947. From that register a case‐cohort sample was selected consisting of all case adoptees, that is those adoptees dying before age 70 years, and a random sample of 1683 adoptees. The survival data of their biological and adoptive parents were collected with the purpose of studying the association of survival between the adoptee and his/her biological or adoptive parents. Motivated by this study, we explored how to make inference in a shared frailty model for case‐cohort data. Our approach was to use inverse probability weighting to account for the sampling in a conditional, shared frailty Poisson model and to use the robust variance estimator proposed by Moger et al. (Statist. Med. 2008; 27:1062–1074).To explore the performance of the estimation procedure, a simulation study was conducted. We studied situations with three types of covariates: one with equal values between families (e.g. generation in parent–offspring pairs), an individual covariate, and one with equal values within each family (e.g. family size).The estimation of the frailty parameter tended to be unbiased; however, a small bias was seen for rare causes of death. The estimation of variance was unbiased when covariates were individual or equal within families, but some overestimation was seen when the covariate was equal between families. As in the earlier analyses, we found that there was a moderate genetic influence on the mortality rate, especially from all causes of death and vascular causes, and we found no effect of familial environment. Copyright © 2010 John Wiley & Sons, Ltd.
Establishing the relationship between nurse staffing and hospital mortality using a clustered discrete‐time logistic model
Authors: Diya L. , Lesaffre E. , Van den Heede K. , Sermeus W. , Vleugels A. 
Published: March 2010

AbstractStudies based on aggregated hospital outcome data have established that there is a relationship between nurse staffing and adverse events. However, this result could not be confirmed in Belgium where 96 per cent of the variability of nurse staffing levels over nursing units (belonging to different hospitals) is explained by within‐hospital variability. To better appreciate the possible impact of nurse staffing levels on adverse events, we propose a multilevel approach reflecting the complex nature of the data. In particular we suggest a clustered discrete‐time logistic model that captures the risks associated with a given unit in the patient's trajectory through the hospital. The model also allows for nurse staffing levels to affect the current and subsequent nursing unit (carry‐over effect). In the model ‘time’ is represented by the sequential number of the nursing unit that the patient is passing through. The model incorporates hospital and nursing unit random effects to express that patients treated in the same hospital and taken care of by nurses of the same unit share a common environment. In this study we used Belgian national administrative databases for the year 2003 to assess the relationship between nurse staffing levels and nurse education variables with in‐hospital mortality. The analysis was restricted to elective cardiac surgery patients. Lower nursing unit staffing levels in the general nursing units were associated with high in‐hospital mortality in units past the traditional cardiac surgery nursing units. Copyright © 2010 John Wiley & Sons, Ltd.
Comparisons of minimization and Atkinson's algorithm
Authors: Senn Stephen , Anisimov Vladimir V. , Fedorov Valerii V. 
Published: March 2010

AbstractSome general points regarding efficiency in clinical trials are made. Reasons as to why fitting many covariates to adjust the estimate of the treatment effect may be less problematic than commonly supposed are given. Two methods of dynamic allocation of patients based on covariates, minimization and Atkinson's approach, are compared and contrasted for the particular case where all covariates are binary. The results of Monte Carlo simulations are also presented. It is concluded that in the cases considered, Atkinson's approach is slightly more efficient than minimization although the difference is unlikely to be very important in practice. Both are more efficient than simple randomization, although it is concluded that fitting covariates may make a more valuable and instructive contribution to inferences about treatment effects than only balancing them. Copyright © 2010 John Wiley & Sons, Ltd.