bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐random autosome segregation: A stepping stone for the evolution of sex chromosome complexes?
Authors: Schwander Tanja , Beukeboom Leo W.
Published: December 2010

A new study in Caenorhabditis elegans shows that homologous autosomes segregate non‐randomly with the sex chromosome in the heterogametic sex. Segregation occurs according to size, small autosomes segregating with, and large autosomes segregating away from the X‐chromosome. Such sex‐biased transmission of autosomes could facilitate the spread of sexually antagonistic alleles whose effects favor the fitness of one sex at the expense of the other. This may provide a first step toward the evolution of new sex determination systems.
Bioengineering of microorganisms for C3 to C5 alcohols production
Authors: Mainguet Samuel E. , Liao James C.
Published: December 2010

Production of renewable fuels and chemicals is an absolute requirement for the sustainability of societies. This fact has been neglected during the past century as cheap and abundant, yet not renewable, sources of hydrocarbons were available. Since fossil fuel availability is decreasing, biological production of fuels and chemicals has been proposed to be a potential alternative to fossil sources. Higher alcohols (from C3 to C5) are useful substitutes for gasoline because of their high energy density and low hygroscopicity and are important feedstocks for other chemicals. Some Clostridia species are known to naturally ferment sugars to isopropanol and 1‐butanol. However, other C3 to C5 alcohols are not produced in large quantities by natural microorganisms. A non‐fermentative strategy to produce a broad range of higher alcohols has been devised using the ubiquitous keto acid biosynthetic pathways. This review provides a current overview of these different strategies.
A highly sensitive LC‐MS/MS method for the determination of S‐raclopride in rat plasma: application to a pharmacokinetic study in rats
Authors: Punde Suresh P. S, Ravindra Ramachandra , Gupta Manish , Dixit Abhishek , Giri Sanjeev , Rajagopal Sriram , Mullangi Ramesh
Published: December 2010

A highly sensitive and rapid assay method has been developed and validated for the estimation of S‐(−)‐raclopride (S‐RCP) in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive ion mode. The assay procedure involves a simple liquid–liquid extraction technique for extraction of S‐RCP and phenacetin (internal standard, IS) from rat plasma. Chromatographic separation was achieved with 0.2% formic acid : acetonitrile (80:20, v/v) at a flow rate of 0.30 mL/min on a Phenomenex Prodigy C18 column with a total run time of 4.5 min. The MS/MS ion transitions monitored were 347.2 → 112.1 for S‐RCP and 180.1 → 110.1 for IS. Method validation and pre‐clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.05 ng/mL and the linearity range was extended from 0.05 to 152 ng/mL in rat plasma. The intra‐day and inter‐day precisions were 0.23–10.5 and 3.74–7.29%, respectively. This novel method was applied to a pharmacokinetic study of S‐RCP in rats. Copyright © 2010 John Wiley & Sons, Ltd.
A rapid and sensitive LC‐MS/MS method for quantification of donepezil and its active metabolite, 6‐o‐desmethyl donepezil in human plasma and its pharmacokinetic application
Authors: Pilli Nageswara Rao , Inamadugu Jaswanth Kumar , Kondreddy Neeraja , Karra Vijaya Kumari , Damaramadugu Rajasekhar , Rao J. V. L. N Seshagiri
Published: December 2010

A rapid and sensitive liquid chromatography–tandem mass spectrometric (LC‐MS/MS) assay method has been developed and fully validated for simultaneous quantification of donepezil and its active metabolite, 6‐o‐desmethyl donepezil in human plasma. Analytes and the internal standard were extracted from human plasma by liquid–liquid extraction technique using a 30:70 v/v mixture of ethyl acetate andn‐hexane. The reconstituted samples were chromatographed on a C18column by using a 70:30 v/v mixture of acetonitrile and ammonium formate (5 mm, pH 5.0) as the mobile phase at a flow rate of 0.6 mL/min. The calibration curve obtained was linear (r≥ 0.99) over the concentration range of 0.09–24.2 ng/mL for donepezil and 0.03–8.13 ng/mL for 6‐o‐desmethyl donepezil. The results of the intra‐day and inter‐day precision and accuracy studies were well within the acceptable limits. The proposed method was successfully applied for the estimation of the drug in real time plasma samples for pharmacokinetic studies. Copyright © 2010 John Wiley & Sons, Ltd.
Validation of a bioanalytical method for the quantification of a therapeutic peptide, ramoplanin, in human dried blood spots using LC‐MS/MS
Authors: Ewles Matthew F. , Turpin Phillip E. , Goodwin Lee , Bakes David M.
Published: December 2010

A method has been developed and validated for the quantification of ramoplanin, a 2554 Da peptide antibiotic, in human dried blood spots using high‐performance liquid chromatography with tandem mass spectrometric detection. The validation data meet FDA acceptance criteria for bioanalytical assays and cover the quantification of ramoplanin over the range 10–5000 ng/mL. The assay determines ramoplanin at the same lower limit of quantification as conventional liquid sample methods. Dried blood spot analysis provides an approach for quantification of peptide therapeutics and delivers significant benefits for sample collection and handling and also sample cleanup over conventional plasma and serum assays. Copyright © 2010 John Wiley & Sons, Ltd.
Recent advances in sample preparation techniques for effective bioanalytical methods
Authors: Kole Prashant Laxman , Venkatesh Gantala , Kotecha Jignesh , Sheshala Ravi
Published: December 2010

This paper reviews the recent developments in bioanalysis sample preparation techniques and gives an update on basic principles, theory, applications and possibilities for automation, and a comparative discussion on the advantages and limitation of each technique. Conventional liquid–liquid extraction (LLE), protein precipitation (PP) and solid‐phase extraction (SPE) techniques are now been considered as methods of the past. The last decade has witnessed a rapid development of novel sample preparation techniques in bioanalysis. Developments in SPE techniques such as selective sorbents and in the overall approach to SPE, such as hybrid SPE and molecularly imprinted polymer SPE, have been addressed. Considerable literature has been published in the area of solid‐phase micro‐extraction and its different versions, e.g. stir bar sorptive extraction, and their application in the development of selective and sensitive bioanalytical methods. Techniques such as dispersive solid‐phase extraction, disposable pipette extraction and micro‐extraction by packed sorbent offer a variety of extraction phases and provide unique advantages to bioanalytical methods. On‐line SPE utilizing column‐switching techniques is rapidly gaining acceptance in bioanalytical applications. PP sample preparation techniques such as PP filter plates/tubes offer many advantages like removal of phospholipids and proteins in plasma/serum. Newer approaches to conventional LLE techniques (salting‐out LLE) are also covered in this review article. Copyright © 2010 John Wiley & Sons, Ltd.
A new method for quantitative determination of two uronic acids by CZE with direct UV detection
Authors: Xia Yong‐gang , Liang Jun , Yang Bing‐you , Wang Qiu‐hong , Kuang Hai‐xue
Published: December 2010

A new method using capillary zone electrophoresis was developed for the rapid quantification of two common uronic acids, galacturonic acid and glucuronic acid, based on utilization of an alkaline background electrolyte with reversed electroosmotic flow (EOF) within 16 min. The method relies on in‐capillary reaction and direct UV detection at the wavelength 270 nm. The optimum electrolyte solution was prepared of 130 mm sodium hydroxide, 36 mm disodium hydrogen phosphate dihydrate and 0.5 mm cetyltrimethylammonium bromide. EOF was reversed to detect uronic acids and to improve the separation of neutral sugars. The established method was validated and the results showed good linearity, high precision and satisfactory sensitivity. The newly developed method was successfully applied to analyze galacturonic acid and glucuronic acid content in Forsythia suspensa polysaccharides. The method is fast since only sample hydrolysis and dilution are required in the sample preparation. Copyright © 2010 John Wiley & Sons, Ltd.
LC‐MS in analytical toxicology: some practical considerations
Authors: Couchman Lewis , Morgan Phillip E.
Published: December 2010

Liquid chromatography, coupled with single‐stage or tandem mass spectrometry, is a powerful tool increasingly used in analytical toxicology. However, the atmospheric pressure ionization processes involved are complex, and subject to interference from matrix components, for example. Further, the techniques used in sample preparation, chromatography and mass analysis are developing rapidly. An understanding of the advantages and limitations of LC‐MS ensures appropriate analyses are performed, and that reliable results are generated. Consideration should be given to the influence of the sample preparation and chromatographic conditions on the ionization of the analyte at the mass spectrometer interface. This review aims to provide some practical guidance and examples to aid method development for commonly encountered analytes in analytical toxicology. Copyright © 2010 John Wiley & Sons, Ltd.
Analysis of acetylcholinesterase inhibitors: bioanalysis, degradation and metabolism
Authors: Azevedo Marques Lygia , Giera Martin , Lingeman Henk , Niessen Wilfried MA
Published: December 2010

Alzheimer's is a neurodegenerative disease. Its symptoms are attributed to a deficiency of cholinergic neurotransmission. The drugs of choice for the treatment of Alzheimer's disease are acetylcholinesterase (AChE) inhibitors. Starting in the 1980's from non‐specific AChE inhibitors, the first‐generation drugs such as physostigmine, a second generation of more selective and better tolerated products has been developed. Methods to detect and quantify these drugs and their metabolites in biological samples have been developed for analysis in plasma, blood, urine and cerebrospinal fluid. Diverse detection techniques have been used, such as ultraviolet, fluorescence, electrochemical and mass spectrometry. In this review, the methods applied to the analysis of these drugs and their metabolites in different biological matrices are reviewed and discussed. The stability of these drugs in biological matrices and under stress‐conditions is also included in the discussion. Copyright © 2010 John Wiley & Sons, Ltd.
Variable selection in regression—a tutorial
Authors: Andersen C. M. , Bro R.
Published: December 2010

This paper provides a practical guide to variable selection in chemometrics with a focus on regression‐based calibration models. Several approaches, such as genetic algorithms (GAs), jack‐knifing, forward selection, etc., are explained; it is also explained how to choose between different kinds of variable selection methods. The emphasis in this paper is on how to use variable selection in practice and avoid the most common pitfalls. Copyright © 2010 John Wiley & Sons, Ltd.
A Thermosensitive Monolithic Column as an Artificial Antibody for the On‐line Selective Separation of the Protein
Authors: Qin Lei , He Xi‐Wen , Jia Man , Li Wen‐You , Zhang Yu‐Kui
Published: December 2010

The main objective of this study was to develop a new methodology for the preparation of a protein (antigen) that is a molecularly imprinted polymer (MIP, an artificial antibody) modified onto the surface of a silica skeleton in which the resulting stationary phase is thermosensitive. The silica monolithic skeleton with vinyl groups was synthesized in a stainless‐steel column by using a mild one‐step sol–gel process with two types of precursor: methyltrimethoxysilane (MTMS) and γ‐methacryloxypropyltrimethoxysilane (γ‐MAPS). Subsequently, three types of the thermosensitive protein MIP were anchored onto the surface of the silica skeleton to prepare the MIP monoliths, which were systematically investigated for back pressure and separation ability at different temperatures to establish good imprinting conditions. Under the optimized imprinting conditions, the chromatographic behavior of the thermosensitive MIP monolith exhibited strong retention ability for the lysozyme template (target antigen) in relation to the nonimprinting monolith (NIP monolith). The imprinting factor (IF) for lysozyme reached 3.48 at 20 °C. Moreover, this new type of artificial antibody displayed favorable binding characteristics for lysozyme over competitive proteins and was further evaluated to selectively separate lysozyme in a real sample by using an on‐line method. The run‐to‐run and column‐to‐column repeatability measurements of the thermosensitive MIP monoliths were also satisfactory.
Structural Design of Easy‐Axis Magnetic Anisotropy and Determination of Anisotropic Parameters of LnIIICuII Single‐Molecule Magnets
Authors: Kajiwara Takashi , Nakano Motohiro , Takahashi Kohei , Takaishi Shinya , Yamashita Masahiro
Published: December 2010

Four dinuclear LnIIICuII complexes with Ln=Tb (1), Dy (2), Ho (3), and Er (4) were synthesized to investigate the relationship between their respective magnetic anisotropies and ligand‐field geometries. These complexes were crystallographically isostructural, and a uni‐axial ligand field was achieved by using three phenoxo oxygen groups. Complexes 1 and 2 displayed typical single‐molecule magnet (SMM) behaviors, of which the out‐of‐phase susceptibilities were observed in the temperature range of 1.8–5.0 K (1) and 1.8–20.0 K (2). The Cole–Cole plots exhibited a semicircular shape with α parameters in the range of 0.08–0.18 (2.6–4.0 K) and 0.07–0.24 (3.5–7.0 K). The energy barriers Δ/kB were estimated from the Arrhenius plots to be 32.9(4) K for 1 and 26.0(5) K for 2. Complex 3 displayed a slow magnetic relaxation below 3.0 K, whereas complex 4 did not show any frequency‐dependent behavior for both in‐phase and out‐of‐phase susceptibilities, which indicates that easy‐axis anisotropy was absent. The temperature dependence of the dc susceptibilities for the field‐aligned samples of 1–3 revealed that the χMT value continuously increased as the temperature was lowered, which indicates the presence of low‐lying Stark sublevels with the highest |Jz| values. In contrast, complex 4 displayed a smaller and temperature‐independent χMT value, which also indicates that easy‐axis anisotropy was absent. Simultaneous analyses were carried out for 1–3 to determine the magnetic anisotropy parameters on the basis of the Hamiltonian that considers B20, B40, and B60.
Stereoselective Total Synthesis of (−)‐Spirofungin A by Utilising Hydrogen‐Bond Controlled Spiroketalisation
Authors: Lynch John E. , Zanatta Shannon D. , White Jonathan M. , Rizzacasa Mark A.
Published: December 2010

The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (−)‐spirofungin A (1) is described. A key step involved a spiroketalisation controlled by an intramolecular H‐bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H‐bond in 4 is possibly due to a 1,5‐alkyne–oxygen interaction. Other key steps include an efficient cross‐metathesis to form the spiroketal precursor, a tin mediated syn‐aldol reaction and a Stille cross‐coupling reaction to create the C22C23 bond. A final Wittig extension followed by deprotection gave (−)‐spirofungin A (1).
Differentiating a Diverse Range of Volatile Organic Compounds with Polyfluorophore Sensors Built on a DNA Scaffold
Authors: Samain Florent , Dai Nan , Kool Eric T.
Published: December 2010

Oligodeoxyfluorosides (ODFs) are short DNA‐like oligomers in which DNA bases are replaced with fluorophores. A preliminary study reported that some sequences of ODFs were able to respond to a few organic small molecules in the vapor phase, giving a change in fluorescence. Here, we follow up on this finding by investigating a larger range of volatile organic analytes, and a considerably larger set of sensors. A library of tetramer ODFs of 2401 different sequences was prepared by using combinatorial methods, and was screened in air for fluorescence responses to a set of ten different volatile organics, including multiple aromatic and aliphatic compounds, acids and bases, varied functional groups, and closely related structures. Nineteen responding sensors were selected and characterized. These sensors were cross‐screened against all ten analytes, and responses were measured qualitatively (by changes in color and intensity) and quantitatively (by measuring ΔR, ΔG, and ΔB values averaged over five to six sensor beads; R=red, G=green, B=blue). The results show that sensor responses were diverse, with a single sensor responding differently to as many as eight of the ten analytes; multiple classes of responses were seen, including quenching, lighting‐up, and varied shifts in wavelength. Responses were strong, with raw ΔR, ΔG, and ΔB values of as high as >200 on a 256‐unit scale and unamplified changes in many cases apparent to the naked eye. Sensors were identified that could distinguish clearly between even very closely related compounds such as acrolein and acrylonitrile. Statistical methods were applied to select a small set of four sensors that, as a pattern response, could distinguish between all ten analytes with high confidence. Sequence analysis of the full set of sensors suggested that sequence/order of the monomer components, and not merely composition, was highly important in the responses.
Preventing failure at school
Authors: Sylva Kathy , Evans Emma
Published: December 2010

This paper considers early educational interventions aimed at preventing school failure. It begins with a typology of prevention and intervention, then goes on to consider four specific examples of preventive interventions all aimed at avoiding or alleviating academic failure at school. (1) The High Scope pre‐school programme for disadvantaged children aimed at providing a ‘better start at school'. (2) Reading Recovery, a targeted intervention aimed at getting children who show early reading difficulties ‘back on course'. (3) A Focused Literacy Programme for improving the reading of all children in disadvantaged neighbourhoods of the inner city. (4) ‘Parent involvement' programmes to improve the reading of all children in primary school through support for literacy at home. Each of the intervention strategies is described and criticised in terms of effectiveness, acceptability and generalisation. Copyright © 1999 John Wiley & Sons, Ltd.
Neighbourhood and preventive strategies with children and families: what works?
Authors: Smith Teresa
Published: December 2010

This paper argues that the 1989 Children Act has provided a poor context for discussing ‘prevention’. The Act has not helped the development of either a proper understanding of childhood disadvantages or policies to deal with it. This paper presents a fresh perspective on ‘prevention’ in the context of Government initiatives such as Sure Start, and argues for analysis of neighbourhood disadvantages and neighbourhood‐based policies. The ‘geography of disadvantage’ has to be understood as well as the facts of disadvantage, that is, the concentrations and persistence of variations in income, health, and educational outcomes as they affect children. Examples of early years programmes and projects are reviewed for their impact on disadvantaged children and their families. Copyright © 1999 John Wiley & Sons, Ltd.
Retracted: The Effect of Early and Intensive Statin Therapy on Ventricular Premature Beat or Nonsustained Ventricular Tachycardia in Patients With Acute Coronary Syndrome
Authors: He Xian‐Zhi , Zhou Sheng‐Hua , Wan Xin‐Hong , Wang Hai‐Yu , Zhong Qing‐Hua , Xue Jian‐Fang
Published: December 2010

Retraction

The following article from Clinical Cardiology, “The Effect of Early and Intensive Statin Therapy on Ventricular Premature Beat or Nonsustained Ventricular Tachycardia in Patients With Acute Coronary Syndrome,”1 by Xian‐Zhi He, MD; Sheng‐Hua Zhou, MD; Xin‐Hong Wan, MD; Hai‐Yu Wang, MD; Qing‐Hua Zhong, MD; and Jian‐Fang Xue, MD, published online on December 10, 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor‐in‐Chief, Dr. A.J. Camm, and Wiley Periodicals, Inc. The retraction has been agreed due to significant overlap with a similar article2 previously published by the same authors in the Cardiology Journal.

References

1. He X.‐Z., Zhou S.‐H., Wan X.‐H., Wang H.‐Y., Zhong Q.‐H. and Xue J.‐F. The effect of early and intensive statin therapy on ventricular premature beat or nonsustained ventricular tachycardia in patients with acute coronary syndrome. Clin Cardiol. 34(1):59–63. doi: 10.1002/clc.20818

2. He XZ, Zhou SH, Wan XH, Wang HY, Zhong QH, Xue JF. The effect of early and intensive statin therapy on ventricular premature beat or non‐sustained ventricular tachycardia in patients with acute coronary syndrome. Cardiol J. 2010;17(4):381–385.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Doublecortin‐positive cells in the adult primate cerebral cortex and possible role in brain plasticity and development
Authors: Bloch Jocelyne , Kaeser Mélanie , Sadeghi Yalda , Rouiller Eric M. , Redmond D. Eugene , Brunet Jean‐François
Published: December 2010

We have demonstrated that cortical cell autografts might be a useful therapy in two monkey models of neurological disease: motor cortex lesion and Parkinson's disease. However, the origin of the useful transplanted cells obtained from cortical biopsies is not clear. In this report we describe the expression of doublecortin (DCX) in these cells based on reverse‐transcription polymerase chain reaction (RT‐PCR) and immunodetection in the adult primate cortex and cell cultures. The results showed that DCX‐positive cells were present in the whole primate cerebral cortex and also expressed glial and/or neuronal markers such as glial fibrillary protein (GFAP) or neuronal nuclei (NeuN). We also demonstrated that only DCX/GFAP positive cells were able to proliferate and originate progenitor cells in vitro. We hypothesize that these DCX‐positive cells in vivo have a role in cortical plasticity and brain reaction to injury. Moreover, in vitro these DCX‐positive cells have the potential to reacquire progenitor characteristics that confirm their potential for brain repair. J. Comp. Neurol. 519:775–789, 2011. © 2010 Wiley‐Liss, Inc.
Computational hemodynamics framework for the analysis of cerebral aneurysms
Authors: Mut Fernando , Löhner Rainald , Chien Aichi , Tateshima Satoshi , Viñuela Fernando , Putman Christopher , Cebral Juan R.
Published: December 2010

Assessing the risk of rupture of intracranial aneurysms is important for clinicians because the natural rupture risk can be exceeded by the small but significant risk carried by current treatments. To this end numerous investigators have used image‐based computational fluid dynamics models to extract patient‐specific hemodynamics information, but there is no consensus on which variables or hemodynamic characteristics are the most important. This paper describes a computational framework to study and characterize the hemodynamic environment of cerebral aneurysms in order to relate it to clinical events, such as growth or rupture. In particular, a number of hemodynamic quantities are proposed to describe the most salient features of these hemodynamic environments. Application to a patient population indicates that ruptured aneurysms tend to have concentrated inflows, concentrated wall shear stress distributions, high maximal wall shear stress, and smaller viscous dissipation ratios than unruptured aneurysms. Furthermore, these statistical associations are largely unaffected by the choice of physiologic flow conditions. This confirms the notion that hemodynamic information derived from image‐based computational models can be used to assess aneurysm rupture risk, to test hypotheses about the mechanisms responsible for aneurysm formation, progression, and rupture, and to answer specific clinical questions. Copyright © 2010 John Wiley & Sons, Ltd.
Community recognition and beliefs about anorexia nervosa and its treatment
Authors: Darby Anita M. , Hay Phillipa J. , Mond Jonathan M. , Quirk Frances
Published: December 2010

Objective:

Mental Health Literacy (MHL), namely recognition, and beliefs about treatment concerning Anorexia Nervosa (AN) were examined in a community sample of male and female (n = 983) aged 15–94 years.

Method:

A vignette describing a women suffering from the symptoms of AN was presented, followed by a respondent‐based structured interview concerning recognition of the problem and treatment beliefs.

Results:

The majority of participants could identify the problem as that of an eating disorder, although only 16.1% could specifically identify it as AN. Many also believed the problem was primarily one of low self‐esteem (32.5%). General practitioners and psychiatrists or psychologists were considered the most helpful treatment providers, while obtaining information about the problem and available services, followed by family therapy, were considered the most helpful treatments. Less than one‐third of participants believed complete recovery was possible. Better AN MHL was found in younger, higher educated, and metropolitan domiciled females.

Discussion:

This study offers encouraging results in regard to AN MHL. In particular, there was moderate regard for the use of mental health specialists in the treatment of the disorder. However, there appears to be a misconception that AN is largely the manifestation of low self‐esteem and confusion concerning the distinction between AN and bulimia nervosa. AN MHL was poorer in males and those with higher social and health disadvantage. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
By how much will the proposed new DSM‐5 criteria increase the prevalence of binge eating disorder?
Authors: Hudson James I. , Coit Caitlin E. , Lalonde Justine K. , Pope Harrison G.
Published: December 2010

Objective:

To estimate how much the prevalence of binge eating disorder will increase under the new proposed DSM‐5 criteria, which relax the requirements for the frequency and duration of eating binges.

Method:

Interview data from a nonclinical sample of 888 first‐degree relatives who had participated in a family study of binge eating disorder were analyzed. The probands in this study (not included in this analysis) had been selected to either have binge eating disorder or no history of eating binges.

Results:

The increase in the prevalence of binge eating disorder using the proposed DSM‐5 criteria relative to the DSM‐IV criteria was 2.9% in women and 3.0% men for lifetime prevalence, and 7.7% in women and 0% in men for the point prevalence.

Discussion:

Changes in frequency and duration of binge episodes proposed for DSM‐5 will likely have only a minimal effect on the prevalence of binge eating disorder. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Memory precursor phenotype of CD8+ T cells reflects early antigenic experience rather than memory numbers in a model of localized acute influenza infection
Authors: Croom Hayley A. , Denton Alice E. , Valkenburg Sophie A. , Swan Natasha G. , Olson Matthew R. , Turner Stephen J. , Doherty Peter C. , Kedzierska Katherine
Published: December 2010

The mechanistic basis of memory T‐cell development is poorly defined. Phenotypic markers that define precursors at effector stages have been characterized for acute systemic infections with high antigen load. We asked whether such markers can identify memory precursors from early effectors (d6) to late memory (>d500) for two immunodominant CD8+ responses during the course of a localized low‐load influenza infection in mice. CD8+ T cells stained with the DbNP366 and DbPA224 tetramers were characterized as IL‐7Rαhi, IL‐7RαhiCD62Lhi or IL‐7RαhiKLRG1lo. While the DbNP366‐ and DbPA224‐specific responses were comparable in size, decay kinetics and memory precursor frequency, their expansion characteristics differed. This correlated with a divergence in the IL‐7Rαhi, IL‐7RαhiCD62Lhi and IL‐7RαhiKLRG1lo phenotypes on effector, but not naïve, CD8+ populations. That effect was abrogated by priming with viruses engineered to present equivalent levels of NP366 and PA224 peptides, indicating that memory phenotypes reflect early antigenic experience rather than memory potential. Thus, the IL‐7RαhiKLRG1lo phenotype had a poor predictive value in identifying memory precursors in the spleen and at the site of infection. Greater consistency in influenza‐specific IL‐7RαhiKLRG1loCD8+ T‐cell numbers was found in draining lymph nodes, suggesting that this may be the preferential site for memory establishment and maintenance following localized virus infections.
Two‐dimensional separation system by on‐line hyphenation of capillary isoelectric focusing with pressurized capillary electrochromatography for peptide and protein mapping
Authors: Wei Juan , Gu Xue , Wang Yan , Wu Yi , Yan Chao
Published: December 2010

A novel on‐line 2‐D system was developed for peptide and protein mapping. The system combines capillary IEF (cIEF) with pressurized CEC (pCEC) using a micro‐injection valve as the interface. Sample fractions, which were focused and separated in the first‐dimension cIEF based on their differences in pIs, were electrically mobilized and further successively resolved by their differences in size, hydrophobicity, and electrophoretic mobility in the second‐dimension pCEC. In the presented system, the valve interface was free of the external electric field in two dimensions for the purpose of stabilization, safety, and facilitating manipulation. In the first dimension, cIEF separation was executed by a one‐step method to simplify the operation procedure. Moreover, a home‐made electrical decoupler was introduced to isolate the micro‐injection valve from the cIEF electric field. For the second dimension, taking advantage of the combination of hydrodynamic flow with EOF, reversed‐phase pCEC not only offers on‐column refocusing the effluent fractions, but also brings enhanced separation resolution and elution speed. Separation effectiveness of this 2‐D system was demonstrated by the analysis of tryptic digest of BSA and human red blood cell lysate. A theoretical peak capacity of approximately 24 000 has been achieved for BSA digest, which proves its promising potential for the application in proteomics.
Sensitized phenotypic screening identifies gene dosage sensitive region on chromosome 11 that predisposes to disease in mice
Authors: Ermakova Olga , Piszczek Lukasz , Luciani Luisa , Cavalli Florence M. G. , Ferreira Tiago , Farley Dominika , Rizzo Stefania , Paolicelli Rosa Chiara , Al‐Banchaabouchi Mumna , Nerlov Claus , Moriggl Richard , Luscombe Nicholas M. , Gross Cornelius
Published: December 2010

The identification of susceptibility genes for human disease is a major goal of current biomedical research. Both sequence and structural variation have emerged as major genetic sources of phenotypic variability and growing evidence points to copy number variation as a particularly important source of susceptibility for disease. Here we propose and validate a strategy to identify genes in which changes in dosage alter susceptibility to disease‐relevant phenotypes in the mouse. Our approach relies on sensitized phenotypic screening of megabase‐sized chromosomal deletion and deficiency lines carrying altered copy numbers of ∼30 linked genes. This approach offers several advantages as a method to systematically identify genes involved in disease susceptibility. To examine the feasibility of such a screen, we performed sensitized phenotyping in five therapeutic areas (metabolic syndrome, immune dysfunction, atherosclerosis, cancer and behaviour) of a 0.8 Mb reciprocal chromosomal duplication and deficiency on chromosome 11 containing 27 genes. Gene dosage in the region significantly affected risk for high‐fat diet‐induced metabolic syndrome, antigen‐induced immune hypersensitivity, ApoE‐induced atherosclerosis, and home cage activity. Follow up studies on individual gene knockouts for two candidates in the region showed that copy number variation inStat5was responsible for the phenotypic variation in antigen‐induced immune hypersensitivity and metabolic syndrome. These data demonstrate the power of sensitized phenotypic screening of segmental aneuploidy lines to identify disease susceptibility genes.

See accompanying Closeup by Cesar P. Canales and Katherina Walz, DOI10.1002/emmm.201000111
Lateral erosion of the Sacramento River, California (1942–1999), and responses of channel and floodplain lake to human influences
Authors: Michalková M. , Piégay H. , Kondolf G.M. , Greco S.E.
Published: December 2010

This study focused on a spatial and temporal analysis of the active channel and associated floodplain lakes using aerial photographs spanning five decades (1942, 1962, 1985, 1999) over a 140 km long reach of the Sacramento. Planimetric changes were analysed longitudinally and temporally to highlight the spatial structures and their evolution through time. The results underline complex changes and space–time pattern in bank erosion, channel length and active channel width. The bank erosion and also channel lengthening were higher between 1962 and 1985 than in the two periods studied before and after. Active channel width significantly decreased from 1942 to 1999; partly progressively from upstream to downstream with local widening whatever the studied periods. Similarly the floodplain lakes observed before 1942–1962 were significantly different in size and geometry from those which appeared during the most recent period. The creation of lakes is less frequent after the 1940s, with a secondary peak of occurrence during the 1962–1985 period. The interpretation of these changes is complex because of various human pressures acting over different time scales (bank protection, flow diversion, sediment starvation, land‐use changes) and various natural influences (flood sequences through out the period, geological setting). The findings are discussed by comparison with previous work, and highlight the important effect of dam impact on peak flow and sediment starvation modifying longitudinally hydraulic conditions within the channel, but also the increase in riprap protection which induced change in bank erosion, channel planimetry and floodplain lake characters (geometry, frequency of renewal). Variation in flood intensities is also observed as having positive effects on the bank erosion pattern. Secondarily, land‐use changes also controlled bank erosion intensity. Copyright © 2010 John Wiley & Sons, Ltd.
The capacity of switchgrass (Panicum virgatum) to degrade atrazine in a phytoremediation setting
Authors: Murphy Ian J , Coats Joel R
Published: December 2010

Atrazine is a widely used herbicide in agriculture. Non-point source contamination of groundwater and drinking water may pose a significant threat to humans, wildlife, and the environment. Phytoremediation may provide a cost-effective strategy for reducing non-point source contamination of atrazine from agricultural runoff. Previous studies have shown that the rhizosphere of the native prairie grass, switchgrass (Panicum virgatum) is capable of enhancing the degradation of atrazine in soils. Biodegradation also may occur within the plant biomass; however, the extent to which this occurs has not been studied. We hypothesize that switchgrass has the capacity to degrade atrazine in vivo, in addition to the microbial biotransformation that occurs in its rhizosphere. The goals of this study were to characterize the ability of switchgrass to take up atrazine from soils, quantify the amount of biodegradation occurring in the plant, and quantify the amount of degradation occurring in the rhizosphere. Switchgrass seedlings were transplanted into autoclaved and non-autoclaved sand containing 10 µg/g atrazine in sand. Treatments were sacrificed on days 0, 3, and 7. Sand and plant tissue extracts were analyzed by gas chromatography to determine the concentration of atrazine and metabolites in sand and plant tissues. Results demonstrated that leaf biomass is capable of detoxifying atrazine, because metabolites were present in leaf material and not in the sand or root. Environ. Toxicol. Chem. 2011; 30:715–722. © 2011 SETAC
A pressure correction‐volume of fluid method for simulation of two‐phase flows
Authors: Lin San‐Yih , Chin Ya‐Hsien , Wu Chun‐Muh , Lin Jeng‐Feng , Chen Yi‐Cheng
Published: December 2010

A pressure correction method coupled with the volume of fluid (VOF) method is developed to simulate two‐phase flows. A volume fraction function is introduced in the VOF method and is governed by an advection equation. A modified monotone upwind scheme for a conservation law (modified MUSCL) is used to solve the solution of the advection equation. To keep the initial sharpness of an interface, a slope modification scheme is introduced. The continuum surface tension (CST) model is used to calculate the surface tension force. Three schemes, central‐upwind, Parker–Youngs, and mixed schemes, are introduced to compute the interface normal vector and the gradient of the volume fraction function. Moreover, a height function technique is applied to compute the local curvature of the interface. Several basic test problems are performed to check the order of accuracy of the present numerical schemes for computing the interface normal vector and the gradient of the volume fraction function. Three physical problems, two‐dimensional broken dam problem, static drop, and spurious currents, and three‐dimensional rising bubble, are performed to demonstrate the efficiency and accuracy of the pressure correction method. Copyright © 2010 John Wiley & Sons, Ltd.
Analysis of a Fuel Cell System by a Step Response
Authors: Jung M. , Ashford M. D. , Williams K. A.
Published: December 2010

A simple method for analysing a fuel cell system using the voltage response to a step change in load resistance is presented in this work. With the modified Randles model, where two resistors and two capacitors are implemented for the Warburg impedance, the response curve is fitted with three exponential curves. Six independent equations corresponding to six parameters of the model can be obtained from the fitted values, and they are solved under two specific assumptions for the initial state. The parameters are the charge double layer capacitance, the charge transfer resistance, a resistor–capacitor pair related to gas diffusion and another pair related to water diffusion. A down curve of the voltage for the step down change in load and an up curve for the step up change are fitted and parameters for both cases are evaluated separately. Analysis is performed by comparing the parameters at different current levels. The impedance is also simulated using the estimated parameters in order to show which parameter is the rate‐determining factor of the fuel cell reaction with increasing current levels.
Planar Solid Oxide Fuel Cell: Electrolyte Deposited by Reactive Magnetron Sputtering and Cell Test
Authors: Coddet P. , Pera M.‐C. , Billard A.
Published: December 2010

In this work the deposition of a thin YSZ electrolyte layer (< 10 μm) on a porous anode substrate is performed by sputtering Zr–Y metallic targets in argon–oxygen reactive gas mixtures under unstable deposition conditions. A plasma emission monitoring system is used to ensure a high deposition rate of the ceramic film. The deposition parameters are optimised in order to obtain a good compromise between quality, density and deposition rate for coatings realised under unstable conditions.

After a short description of the experimental setup, the characterisation of the YSZ coatings is performed using scanning electron microscopy, X‐ray diffraction and permeability measurements. Then a complete cell incorporating a thin YSZ electrolyte layer (6.2 ± 0.3 μm thick) obtained by magnetron sputtering is manufactured and tested. This single planar solid oxide fuel cell exhibits a power density of 560 mW cm–2under a voltage of 0.7 V at 800 °C and a maximal power density of 660 mW cm–2is reached.
Risk factors for postoperative cognitive and functional difficulties in abdominal aortic aneurysm patients: a three month follow‐up
Authors: Wallbridge Harold R. , Benoit Archie G. , Staley Douglas , Ediger Jason P. , Campbell Barry I.
Published: December 2010

Background

Cognitive impairment and deficits in functional performance are major concerns following surgery, particularly for older patients. The objective of this study was to examine predictors of postoperative cognitive and functional difficulties and explore the relationship between presurgery and postsurgery cognitive ability and functional performance.

Methods

89 patients undergoing elective abdominal aortic aneurysm (AAA) surgery were administered a battery of cognitive measures preoperatively, at the time of discharge from hospital and 3 months postoperatively. Functional performance was evaluated by the Portland Adaptability Inventory (PAI), both pre and postsurgery. Symptoms of delirium were assessed during the first six postoperative days.

Results

A diagnosis of delirium had a mild effect on functional performance 3 months postoperatively. The strongest predictors of postoperative functional performance were the level of functioning presurgery, a longer length of hospital stay and the total number of days delirious. Cognitive impairment postsurgery was predicted by presurgery cognitive measures of verbal memory and psychomotor speed performance and the total number of days delirious.

Conclusions

Functional performance outcomes for AAA patients 3 months postsurgery revealed no significant loss of functioning relative to presurgery levels, although longer length of hospital stay and greater number of days delirious was associated with somewhat poorer outcome on indicators of social and physical functioning. Cognitive impairment postoperatively was fairly mild but when it was found it was associated with number of days delirious and preoperative deficits in verbal memory and psychomotor speed. Copyright © 2010 John Wiley & Sons, Ltd.
Development of consensus guidelines for venous thromboembolism prophylaxis in patients undergoing microvascular reconstruction of the mandible
Authors: Deleyiannis Frederic W.‐B. , Clavijo‐Alvarez Julio A. , Pullikkotil Benson , Zanoun Rami , Behringer Tiffany , Chong Tae W. , Rubin J. Peter , Johnson Jonas T.
Published: December 2010

Background

The purpose of this study was to determine how guidelines for venous thromboembolism prophylaxis can be applied to patients undergoing microsurgical reconstruction of the mandible.

Methods

Retrospective review of our institutional use of thromboprophylaxis and the associated outcomes in 114 patients (58 free fibular flaps and 56 osteocutaneous radial forearm flaps).

Results

Twenty‐two patients (19.3%) received only intermittent pneumatic compression. Overall, 80.7% received postoperative chemoprophylaxis. Sixty‐four percent initiated chemoprophylaxis within 24 hours after surgery. Only 13.2% received the recommended frequency of chemoprophylaxis. One patient had development of a pulmonary embolism. Four patients undergoing chemoprophylaxis had development of neck hematomas; in each case the cause of bleeding could be attributed to a cause distinct from chemoprophylaxis.

Conclusions

No consistent chemoprophylaxis protocol was followed. Chemoprophylaxis was not associated with an increased risk of bleeding. Physician education is the next step in decreasing variations in chemoprophylaxis and adopting guidelines similar to The American College of Chest Physicians. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Localization‐specific LKB1 loss in head and neck squamous cell carcinoma metastasis
Authors: Kline Erik R. , Muller Susan , Pan Lin , Tighiouart Mourad , Chen Zhuo (Georgia) , Marcus Adam I.
Published: December 2010

Background

LKB1 loss is associated with invasive carcinoma and metastasis. In head and neck squamous cell carcinoma (HNSCC), lymph node metastasis status is the strongest predictor of survival.

Methods

LKB1 immunohistochemistry was performed on primary tumors from patients with HNSCC who never developed metastases, patients with metastases, and their paired lymph node metastasis to determine whether LKB1 was associated with HNSCC metastasis.

Results

LKB1 was expressed in the nucleus and cytoplasm of tumor cells and HNSCC cell lines. Primary tumors from patients with metastatic carcinoma had decreased nuclear, but not cytoplasmic, LKB1 compared to patients with nonmetastatic cancer. Nuclear LKB1 levels correlated with lymph node metastasis grade and primary tumor site. The percentage of tumor cells negative for nuclear LKB1 staining was greatest in the primary metastatic tumor group, and decreased nuclear LKB1 trended toward worse disease‐free survival.

Conclusion

Decreased nuclear LKB1 levels correlate with HNSCC metastasis and suggest a nuclear function of LKB1 in repressing HNSCC metastasis. Head Neck, 2010
Tumor necrosis factor (TNF)‐α, soluble TNF receptors and endometrial cancer risk: The EPIC study
Authors: Dossus Laure , Becker Susen , Rinaldi Sabina , Lukanova Annekatrin , Tjønneland Anne , Olsen Anja , Overvad Kim , Chabbert‐Buffet Nathalie , Boutron‐Ruault Marie‐Christine , Clavel‐Chapelon Françoise , Teucher Birgit , Chang‐Claude Jenny , Pischon Tobias , Boeing Heiner , Trichopoulou Antonia , Benetou Vasiliki , Valanou Elisavet , Palli Domenico , Sieri Sabina , Tumino Rosario , Sacerdote Carlotta , Galasso Rocco , Redondo Maria‐Luísa , Bonet Catalina Bonet , Molina‐Montes Esther , Altzibar Jone M. , Chirlaque Maria‐Dolores , Ardanaz Eva , Bas Bueno‐de‐Mesquita H. , van Duijnhoven Fränzel J.B. , Peeters Petra H.M. , Charlotte Onland‐Moret N. , Lundin Eva , Idahl Annika , Khaw Kay‐Tee , Wareham Nicholas , Allen Naomi , Romieu Isabelle , Fedirko Veronika , Hainaut Pierre , Romaguera Dora , Norat Teresa , Riboli Elio , Kaaks Rudolf
Published: December 2010

Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor‐α (TNF‐α), one of the major pro‐inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case‐control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF‐α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two‐hundred‐seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two‐sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF‐α (odds ratio [OR]: 1.73, 95% CI: 1.09‐2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99‐2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92‐2.55, Ptrend = 0.03) after adjustment for body‐mass‐index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C‐peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF‐α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.