bluuebunny/crossref_metadata_2025 huggingface dataset:
Escherichia coli K‐12 (pEGFPluxABCDEamp): a tool for analysis of bacterial killing by antibacterial agents and human complement activities on a real‐time basis
Authors: Atosuo Janne , Lehtinen Janne , Vojtek Libor , Lilius Esa‐Matti
Published: November 2012

Photorhabdus luminescens luxCDABE genes were integrated into E. coli K‐12 using a high copy number plasmid containing modified luxABCDE genes under the control of the powerful Lac promoter. This strain emitted 10 times higher bioluminescence (BL) than P. luminescens. BL production under different growth conditions was studied. In both bacterial strains, the increase in BL signal correlated with the increase in optical density (OD) in a rich growth medium. However, at the logarithmic growth phase, the BL signal was roughly constant. By contrast, in minimal growth media, there was no substantial growth and the BL/cell was approximately five times higher than in the rich medium. The dynamic measurement range of BL was 102–107 colony‐forming units (CFU) in E. coli and 103–107 CFU in P. luminescens. Because the decrease in the BL signal correlated with the decrease in CFU and OD, i.e. the number of bacterial cells killed, it proved to be very suitable for assessing the antibacterial effects of different antimicrobial agents. Unlike with plate counting, the kinetics of killing can be monitored on a real‐time basis using BL measurements. Complement activities in different samples can be estimated using only one serum dilution. The transformed E. coli strain appeared to be superior to P. luminescens in these applications because E. coli was complement sensitive, the detection limit of E. coli was one order lower and the BL‐producing system of P. luminescens appeared to be quite unstable. Copyright © 2012 John Wiley & Sons, Ltd.
Treatment of recurrent intrahepatic cholangiocarcinoma
Authors: Sulpice L , Rayar M , Boucher E , Pracht M , Meunier B , Boudjema K
Published: November 2012

Background

The aims of this study were to evaluate risk factors for recurrence following hepatectomy with curative intent for intrahepatic cholangiocarcinoma (ICC), and predictors of survival after intrahepatic recurrence.

Methods

All patients with ICC who underwent liver resection between January 1997 and August 2011 in a single centre were analysed retrospectively. Clinicopathological factors likely to influence recurrence and postrecurrence survival were assessed by univariable and multivariable analysis.

Results

A total of 87 patients were analysed. R0 resection was achieved in 65 patients (75 per cent). Eighty-three patients survived more than 1 month after resection. Median survival was 33 months, with 1-, 3- and 5-year actuarial survival rates of 79, 47 and 31 per cent respectively. Recurrence occurred in 45 (54 per cent) of the 83 patients, most frequently in the liver (25 patients). Satellite nodules (odds ratio (OR) 8·17, 95 per cent confidence interval 1·38 to 48·53; P = 0·021), hilar lymph node metastases (OR 5·24, 1·07 to 25·75; P = 0·041) and perineural invasion (OR 9·68, 1·07 to 87·54; P = 0·043) were identified as independent risk factors for recurrence. Repeat hepatectomy (P = 0·003) and intra-arterial yttrium-90 radiotherapy (P = 0·048) were associated with longer survival after intrahepatic recurrence.

Conclusion

Satellite nodules, hilar lymph node metastases and perineural invasion are risk factors for recurrence following resection with curative intent for ICC. Repeat hepatectomy and labelled yttrium-90 radiotherapy may improve survival after intrahepatic recurrence.
Robotic cancer surgery
Authors: Sodergren M H , Darzi A
Published: November 2012

Surgery of the future
Synthesis of Glycopolymers by Controlled Radical Polymerization Techniques and Their Applications
Authors: Vázquez‐Dorbatt Vimary , Lee Juneyoung , Lin En‐Wei , Maynard Heather D.
Published: November 2012

Natural saccharides are involved in numerous biological processes. It has been shown that these carbohydrates play a role in cell adhesion and proliferation, as well as protein stabilization, organization, and recognition. Certain carbohydrates also serve as receptors for viruses and bacteria. They are over expressed in diseases such as cancer. Hence, a lot of effort has been focused on mimicking these sugars. Polymers with pendent saccharide groups, also known as glycopolymers, are studied as oligo‐ and polysaccharide mimics. Controlled radical polymerization (CRP) techniques such as atom transfer radical polymerization (ATRP), reversible addition–fragmentation chain transfer (RAFT) polymerization, and nitroxide‐mediated polymerization (NMP), as well as cyanoxyl‐mediated free radical polymerization have allowed chemists to synthesize well‐defined glycopolymers that, in some cases, have particular end‐group functionalities. This review focuses on the synthesis of glycopolymers by these methods and the applications of glycopolymers as natural saccharide mimics.
Mesoporous Borated Zirconia: A Solid Acid–Base Bifunctional Catalyst
Authors: Sinhamahapatra Apurba , Pal Provas , Tarafdar Abhijit , Bajaj Hari C. , Panda Asit Baran
Published: November 2012

The development and use of reusable solid catalysts for the selective organic transformation in solvent‐free or environmentally benign solvent media is the key interest of modern frontier science. Herein a facile low temperature aqueous solution based chemical route for the synthesis of mesoporous borated zirconia, an acid–base bifunctional solid catalyst, using aqueous zirconium ammonium carbonate complex and borax in presence of cetyltrimethylammonium bromide is presented. The material has a very high surface area and acidity with weak basicity. The catalytic activity of the material was investigated for the solvent‐free Knoevenagel condensation reaction of benzaldehyde/substituted benzaldehyde and malononitrile/cyano ethylacetate to confirm the acid–base bifunctionality. High yield (>90 %) of the corresponding benzylidene was obtained within 15–30 min at room temperature. The evidence that the high catalytic activity is a result of acid–base bifunctionality of the synthesized borated zirconia material was further supported by performing Claisen–Schmidt condensation of benzaldehyde and acetophenone. The methodology was also extended for targeted synthesis of cinnamyl ethyl ester and coumarin or coumarin ester; and resulted in a good yield.
Hydrothermal Synthesis of Copper Hydroxyphosphate Hierarchical Architectures
Authors: Xu J. , Zhang J. , Liu X.
Published: November 2012

Copper hydroxyphosphate, Cu2(OH)PO4, with six hierarchical architectures was successfully synthesized through a hydrothermal route. The resulting hierarchical superstructures were characterized using powder X‐ray diffraction and scanning electron microscopy. In this hydrothermal process, the morphology of copper hydroxyphosphate changed drastically with the addition of different amounts of alcohol (ethanol, n‐propanol, or ethylene glycol) as solvent. A possible mechanism for the formation of these copper hydroxyphosphate hierarchical superstructures is proposed. This approach provides a facile strategy to synthesize copper hydroxyphosphate crystals with unique morphologies and complex architectures. This binary reaction medium (alcohol and water) could provide an alternative and versatile strategy for controlling inorganic microcrystals by manipulating the supersaturation of the growing solution.
Rational Design of a Nonbasic Molecular Receptor for Selective NH4+/K+ Complexation in the Gas Phase
Authors: Rueda‐Zubiaurre Ainoa , Herrero‐García Noelia , del Rosario Torres María , Fernández Israel , Osío Barcina José
Published: November 2012

A new molecular receptor (1) for ammonium recognition has been designed and constructed by using only carbon atoms. This molecular receptor can co‐exist in two different isoenergetic conformations but, upon complexation, the conformers are no longer isoenergetic, and a basket‐shaped conformation becomes clearly more stable. The pre‐organised tetrahedral structure of this basket‐shaped molecule favours the complexation of ammonium ions by NH⋅⋅⋅π interactions with the four phenyl groups of the host. A similar behaviour is not observed in a similar, but less pre‐organised, reference molecule. ESI‐MS competition experiments show that 1 is able to bind NH4+ over K+ selectively. This is the first example of a neutral molecular receptor that shows a remarkable NH4+/K+ selectivity. DFT‐calculations provide insight into the nature of host–guest interactions of both 1⋅NH4+ and 1⋅K+ complexes as well as in the mechanism involved in multiple cation–π interactions and the influence of these interactions on the conformational stability and the selective binding of the host.
Fisher information matrix: A tool for dimension reduction, projection pursuit, independent component analysis, and more
Authors: Lindsay Bruce G. , Yao Weixin
Published: November 2012

Hui & Lindsay (2010) proposed a new dimension reduction method for multivariate data. It was based on the so‐called white noise matrices derived from the Fisher information matrix. Their theory and empirical studies demonstrated that this method can detect interesting features from high‐dimensional data even with a moderate sample size. The theoretical emphasis in that paper was the detection of non‐normal projections. In this paper we show how to decompose the information matrix into non‐negative definite information terms in a manner akin to a matrix analysis of variance. Appropriate information matrices will be identified for diagnostics for such important modern modelling techniques as independent component models, Markov dependence models, and spherical symmetry. The Canadian Journal of Statistics 40: 712–730; 2012 © 2012 Statistical Society of Canada
Two‐Photon Fluorescent Imaging of Myelination in the Spinal Cord
Authors: Condie Allison G. , Gerson Stanton L. , Miller Robert H. , Wang Yanming
Published: November 2012

Myelination is a fundamental biological process in the vertebrate nervous system. Damage to or malformation of myelin can lead to various neurological diseases; for example, demyelination in the spinal cord is a major cause of paralysis of patients suffering from multiple sclerosis and related diseases. The ability to directly track myelin levels in the spinal cord is needed in order to assess the efficacy of therapeutics in promoting myelin repair. To address this unmet need, 4‐((E)‐4‐((E)‐4‐aminostyryl)‐2,5‐dimethoxystyryl)‐N‐methylaniline, known as Case Imaging Compound (CIC), has been developed as a myelin‐targeted fluorescent imaging agent that selectively binds to myelin. CIC was synthesized via an improved route and evaluated as a fluorescent probe for two‐photon fluorescent imaging of myelin in the spinal cord in both demyelinated and dysmyelinated models. In vitro and ex vivo tissue staining both suggest that CIC selectively binds to in animal models. Further evaluation in animal models indicated that CIC is sensitive to differences in myelin content in healthy versus pathological myelin. CIC could potentially be useful in the development and evaluation of novel therapies for multiple sclerosis and other demyelinating diseases.
Effect of C7 Modifications on Benzothiadiazine‐1,1‐dioxide Derivatives on Their Inhibitory Activity and Selectivity toward Aldose Reductase
Authors: Zhang Shuzhen , Chen Xin , Parveen Shagufta , Hussain Saghir , Yang Yanchun , Jing Chaojun , Zhu Changjin
Published: November 2012

The development and progression of chronic complications in diabetic patients, such as retinopathy, nephropathy, neuropathy, cataracts, and stroke, are related to the activation and/or overexpression of aldose reductase (ALR2), which is a member of the aldo–keto reductase superfamily. A structure–activity relationship study focused on the C7 position of 1,2,4‐benzothiadiazine‐1,1‐dioxide derivatives was pursued in an attempt to discover ALR2 inhibitors with enhanced potency and selectivity. These studies led to a series of new C7‐substituted compounds, which were evaluated for their inhibitory activity against ALR2; they exhibited IC50 values in the range of 2.80–45.13 nM. Two compounds with a C7‐dimethylcarbamoyl and a C7‐diethylcarbamoyl substituent, respectively, were found to be the most active and presented excellent selectivity for ALR2 over aldehyde reductase (ALR1). The structure–activity relationship analyses and molecular modeling studies presented herein highlight the importance of hydrophobic and bulky groups at the C7 position for inhibitory activity and selectivity toward ALR2.
High expression of Dickkopf‐related protein 1 is related to lymphatic metastasis and indicates poor prognosis in intrahepatic cholangiocarcinoma patients after surgery
Authors: Shi Ruo‐Yu , Yang Xin‐Rong , Shen Qiu‐Jin , Yang Liu‐Xiao , Xu Yang , Qiu Shuang‐Jian , Sun Yun‐Fan , Zhang Xin , Wang Zheng , Zhu Kai , Qin Wen‐Xin , Tang Zhao‐You , Fan Jia , Zhou Jian
Published: November 2012

BACKGROUND:

Dickkopf‐related protein 1 (DKK1) has been reported involved in metastasis and invasion in several tumors. This study sought to investigate the prognostic value of DKK1 in intrahepatic cholangiocarcinoma (ICC) and its role in promoting ICC metastasis.

METHODS:

Tissue microarrays of 138 ICC patient samples were employed to detect DKK1, vascular endothelial growth factor C (VEGF‐C), and matrix metalloproteinase 9 (MMP9) expression using immunohistochemistry. The prognostic significances were assessed by Kaplan‐Meier survival estimates. DKK1 expression was measured in an ICC cell line (HCCC‐9810) and ICC tissues by immunofluorescence assay, quantitative real‐time polymerase chain reaction, and western blot. Serum levels of DKK1 from 37 ICC patients were tested by enzyme‐linked immunosorbent assay. The role of DKK1 in proliferation, migration, invasion, and gene expression regulation was assessed by DKK1 depletion using small interfering RNA.

RESULTS:

Multivariate analyses revealed that DKK1 was an unfavorable predictor for overall survival and time to recurrence. The prognostic significance was retained in ICC patients with low recurrence risk (P < .05). DKK1 expression was elevated in an ICC cell line, tumor samples, and patient sera. High levels of DKK1 in ICC tissues correlated with elevated MMP9, VEGF‐C, and metastasis of hepatic hilar lymph nodes. DKK1 depletion caused a decrease in cell migration and invasiveness, and down‐regulation of MMP9 and VEGF‐C expression.

CONCLUSIONS:

DKK1 is a novel prognostic biomarker for ICC, and it enhances tumor cell invasion and promotes lymph node metastasis of ICC through the induction of MMP9 and VEGF‐C. DKK1 may be a potential therapeutic target for ICC. Cancer 2013. © 2012 American Cancer Society.
Changing trends in radiation therapy technologies in the last year of life for patients diagnosed with metastatic cancer in the United States
Authors: Guadagnolo B. Ashleigh , Huo Jinhai , Liao Kai‐Ping , Buchholz Thomas A. , Das Prajnan
Published: November 2012

BACKGROUND:

Our goal was to investigate utilization trends for advanced radiation therapy (RT) technologies, such as intensity‐modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS), in the last year of life among patients diagnosed with metastatic cancer.

METHODS:

We used the Surveillance, Epidemiology and End Results (SEER)‐Medicare linked databases to analyze claims data in the last 12 months of life for 64,525 patients diagnosed with metastatic breast, colorectal, lung, pancreas, and prostate cancers from 2000 to 2007. Logistic regression modeling was conducted to analyze potential demographic, health services, and treatment‐related variables' influences on receipt of advanced RT.

RESULTS:

Among the 19,161 (29.7%) patients who received radiation therapy, there was a significant decrease in the proportion of patients who received the simplest radiation technique (ie, 2D‐radiation therapy) (P < .0001), and significant increases in the proportions of patients receiving more advanced radiation techniques (ie, IMRT, and SRS; P < .0001 for all curves); although the rates for use of IMRT and SRS in 2007 remained under 5%. On multivariate analyses, receipt of RT varied significantly by non‐clinical characteristics such as race, marital status, neighborhood income, and SEER region. Patients who received hospice care in the last year of life were more likely to receive radiation therapy (OR = 1.35, 95% CI = 1.30‐1.40) but less likely to be treated with IMRT (OR = 0.76, 95% CI = 0.62‐0.92).

CONCLUSIONS:

Although the proportion of patients receiving RT in the last year of life for metastatic cancer did not change for most of the past decade, we observed significant trends toward more advanced radiation techniques. Cancer 2013. © 2012 American Cancer Society.
Matrix‐Isolated Hydrogen‐Bonded and Van der Waals Complexes of Hydrogen Peroxide with OCS and CS2
Authors: Grzechnik Katarzyna , Mierzwicki Krzysztof , Mielke Zofia
Published: November 2012

Matrix isolation spectroscopy has been combined with ab initio calculations to characterize the 1:1 complexes of H2O2 with OCS and CS2. The infrared spectra of the argon and nitrogen matrices doped with H2O2 and OCS or CS2 have been measured and analyzed. The geometries of the complexes were optimized at the MP2/6‐311++G(3df,3pd) level of theory. Four structures were found for the OCS‐H2O2 complex and five for the CS2‐H2O2 one; every pair of the corresponding structures showed close correspondence. For every optimized structure the interaction energy was partitioned according to the SAPT Scheme and the topological distribution of the charge density (AIM theory) was performed. The SAPT analysis and AIM results indicate that only one complex among the nine optimized ones is stabilized by the hydrogen bonding, namely the OCS‐H2O2 one with the OH group of H2O2 bonded to an oxygen atom of OCS. The other structures are stabilized by van der Waals interaction. The spectra analysis evidences that at least two types of the complexes are trapped in the argon matrices including the most stable ones: hydrogen bonded structure in the case of the OCS‐H2O2 complex and the structure stabilized by the S⋅⋅⋅H and C⋅⋅⋅O interactions in the case of the CS2‐H2O2 complex. The solid nitrogen environment triggers the formation of the structures of C2v symmetry with a sulfur atom of OCS or CS2 directed toward the center of OO bond of H2O2, stabilized by S⋅⋅⋅O interactions.
Exploring the Psychological Processes Underlying Touch: Lessons from the Alexander Technique
Authors: Jones T. , Glover L.
Published: November 2012

The experience of touch is significant; both in its positive implications and in how it attracts caution and controversy. Accordingly, physical contact within psychological therapy has been shown to improve well‐being and the therapeutic relationship, yet the majority of therapists never or rarely use touch. This research aimed to explore psychological processes underlying touch through the Alexander Technique, a psycho‐physical technique taught one to one using touch. Six individuals who had received the Alexander Technique were interviewed, and 111 completed surveys. Interview data suggested an incompatibility between touch and the spoken word, which was understood through the way touch lacks verbal discourses in our society. The largely simplistic and dichotomous verbal understanding we have (either only very positive or very negative) could help understand some of the societal‐level caution surrounding touch. Touch was seen also as a nurturing experience by interviewees, which influenced inter‐personal and intra‐personal relational processes. Developmental models were used to frame the way touch strengthened the pupil–teacher relationship and the way pupils' intra‐personal psychological change seemed linked to this relational experience. The surveys largely supported these findings, and discussion is made around the notable way pupils negatively interpreted the intention of the survey. Implications for the use of touch in psychological therapies are discussed, as are limitations and ideas for future research. Copyright © 2012 John Wiley & Sons, Ltd.

Key Practitioner Message

Touch is a powerful experience, and physical contact within psychological therapy has been shown to improve well‐being and the therapeutic relationship, yet the majority of therapists never or rarely use touch.

The AT is an alternative therapeutic approach to psycho‐physical well‐being that offers an interesting model to study the impact of touch.

Findings from those that have used the technique reaffirmed that touch can improve well‐being and can be a powerful force in the ‘therapeutic relationship’. Accounts drew strong parallels with developmental experiences, which may be of particular interest to those working psychodynamically.

Findings also highlighted the lack of discourses our culture has for touch and how the ones we share can be super‐imposed onto experiences. This should be kept in mind when discussing all types of physical contact with clients.

Outcomes from AT pupils cannot be generalized to those seeking psychological support; however, the findings accentuated the power of holistic working. This is important as we begin to understand more around how emotions are held in the body.
Granular Bamboo‐Derived Activated Carbon for High CO2 Adsorption: The Dominant Role of Narrow Micropores
Authors: Wei Haoran , Deng Shubo , Hu Bingyin , Chen Zhenhe , Wang Bin , Huang Jun , Yu Gang
Published: November 2012

Cost‐effective biomass‐derived activated carbons with a high CO2 adsorption capacity are attractive for carbon capture. Bamboo was found to be a suitable precursor for activated carbon preparation through KOH activation. The bamboo size in the range of 10–200 mesh had little effect on CO2 adsorption, whereas the KOH/C mass ratio and activation temperature had a significant impact on CO2 adsorption. The bamboo‐derived activated carbon had a high adsorption capacity and excellent selectivity for CO2, and also the adsorption process was highly reversible. The adsorbed amount of CO2 on the granular activated carbon was up to 7.0 mmol g−1 at 273 K and 1 bar, which was higher than almost all carbon materials. The pore characteristics of activated carbons responsible for high CO2 adsorption were fully investigated. Based on the analysis of narrow micropore size distribution of several activated carbons prepared under different conditions, a more accurate micropore range contributing to CO2 adsorption was proposed. The volume of micropores in the range of 0.33–0.82 nm had a good linear relationship with CO2 adsorption at 273 K and 1 bar, and the narrow micropores of about 0.55 nm produced the major contribution, which could be used to evaluate CO2 adsorption on activated carbons.
Musashi1‐CreERT2: A new cre line for conditional mutagenesis in neural stem cells
Authors: Takeda Haruna , Koso Hideto , Tessarollo Lino , Copeland Neal G. , Jenkins Nancy A.
Published: November 2012

The RNA‐binding protein Musashi1 (Msi1) is one of two mammalian homologues of DrosophilaMusashi, which is required for the asymmetric cell division of sensory organ precursor cells. In the mouse central nervous system (CNS), Msi1 is preferentially expressed in mitotically active progenitor cells in the ventricular zone (VZ) of the neural tube during embryonic development and in the subventricular zone (SVZ) of the postnatal brain. Previous studies showed that cells in the SVZ can contribute to long‐term neurogenesis in the olfactory bulb (OB), but it remains unclear whether Msi1‐expressing cells have self‐renewing potential and can contribute to neurogenesis in the adult. Here, we describe the generation of Msi1‐CreERT2 knock‐in mice and show by cell lineage tracing that Msi1‐CreERT2‐expressing cells mark neural stem cells (NSCs) in both the embryonic and adult brain. Msi1‐CreERT2 mice thus represent a new tool in our arsenal for genetically manipulating NSCs, which will be essential for understanding the molecular mechanisms underlying neural development. genesis, 51:128–134, 2013. © 2012 Wiley Periodicals, Inc.
Commentary on ‘Medical interventions for treating anthracycline‐induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer’
Authors: Chow Eric J.
Published: November 2012

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Sieswerda E, van Dalen EC, Postma A, Cheuk DKL, Caron HN, Kremer LCM. Medical interventions for treating anthracycline‐induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD008011. DOI: 10.1002/14651858.CD008011.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Deglaciation explains bat extinction in the Caribbean
Authors: Dávalos Liliana M. , Russell Amy L.
Published: November 2012

Ecological factors such as changing climate on land and interspecific competition have been debated as possible causes of postglacial Caribbean extinction. These hypotheses, however, have not been tested against a null model of climate‐driven postglacial area loss. Here, we use a new Quaternary mammal database and deep‐sea bathymetry to estimate species–area relationships (SARs) at present and during the Last Glacial Maximum (LGM) for bats of the Caribbean, and to model species loss as a function of area loss from rising sea level. Island area was a significant predictor of species richness in the Bahamas, Greater Antilles, and Lesser Antilles at all time periods, except for the Lesser Antilles during the LGM. Parameters of LGM and current SARs were similar in the Bahamas and Greater Antilles, but not the Lesser Antilles, which had fewer estimated species during the LGM than expected given their size. Estimated postglacial species losses in the Bahamas and Greater Antilles were largely explained by inferred area loss from rising sea level in the Holocene. However, there were more species in the Bahamas at present, and fewer species in the smaller Greater Antilles, than expected given island size and the end‐Pleistocene/early Holocene SARs. Poor fossil sampling and ecological factors may explain these departures from the null. Our analyses illustrate the importance of changes in area in explaining patterns of species richness through time and emphasize the role of the SAR as a null hypothesis in explorations of the impact of novel ecological interactions on extinction.
Converting a Birch Reduction Product into a Polyketide: Application to the Synthesis of a C1–C11 Building Block of Rimocidin
Authors: Nachbauer Luc , Brückner Reinhard
Published: November 2012

A stereoselective synthesis of a C1–C11 building block for the polyol‐polyene antibiotic rimocidin has been developed. Its functional groups originate from a disubstituted indane, which underwent Birch reduction, and oxidative cleavage. This provided a dihydropyranone with a β‐keto ester side‐chain. The latter was subjected to a Noyori hydrogenation (ds > 97:3). An oxy‐Michael addition gave a mixture of two spiroketals. Luche reduction then led to three spiroketals in an 80:10:10 ratio. The major spiroketal became isolable by separating one of the by‐products chromatographically and the other by a diastereomer‐selective thioketalization. The remaining spiroketal was ring‐opened to give a dithiolane. Its CO2Me group was converted into the 1,3‐dithiane unit of the target compound (i.e., 47) using an odor‐reducing work‐up procedure, which should prove to be generally useful.
Two‐phase electro‐hydrodynamic flow modeling by a conservative level set model
Authors: Lin Yuan
Published: November 2012

The principles of electro‐hydrodynamic (EHD) flow have been known for more than a century and have been adopted for various industrial applications, for example, fluid mixing and demixing. Analytical solutions of such EHD flow only exist in a limited number of scenarios, for example, predicting a small deformation of a single droplet in a uniform electric field. Numerical modeling of such phenomena can provide significant insights about EHDs multiphase flows. During the last decade, many numerical results have been reported to provide novel and useful tools of studying the multiphase EHD flow. Based on a conservative level set method, the proposed model is able to simulate large deformations of a droplet by a steady electric field, which is beyond the region of theoretic prediction. The model is validated for both leaky dielectrics and perfect dielectrics, and is found to be in excellent agreement with existing analytical solutions and numerical studies in the literature. Furthermore, simulations of the deformation of a water droplet in decyl alcohol in a steady electric field match better with published experimental data than the theoretical prediction for large deformations. Therefore the proposed model can serve as a practical and accurate tool for simulating two‐phase EHD flow.
Development of a CD‐MEKC method for investigating the metabolism of tamoxifen by flavin‐containing monooxygenases and the inhibitory effects of methimazole, nicotine and DMXAA
Authors: Yeniceli Duygu , Deng Xiaolan , Adams Erwin , Dogrukol‐Ak Dilek , Schepdael Ann Van
Published: November 2012

A selective and low‐cost CD‐MEKC method under acidic conditions was developed for investigating the N‐oxygenation of tamoxifen (TAM) by flavin‐containing monooxygenases (FMOs). The inhibitory effects of methimazole (MMI), nicotine and 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA) on the given FMO reaction were also evaluated; 100 mM phosphate buffer (pH 8.6) was used for performing the enzymatic reaction and the separation of TAM and its metabolite tamoxifen N‐oxide (TNO) was obtained with a BGE consisting of 100 mM phosphoric acid solution adjusted to pH 2.5 with triethanolamine containing 50 mM sodium taurodeoxycholate, 20 mM carboxymethyl β‐CD and 20% ACN. The proposed method was applied for the kinetics study of FMO1 using TAM as a substrate probe. A Michaelis–Menten constant (Km) of 164.1 μM was estimated from the corrected peak area of the product, TNO. The calculated value of the maximum reaction velocity (Vmax) was 3.61 μmol/min/μmol FMO1; 50% inhibitory concentration and inhibition constant (Ki) of MMI, the most common alternate substrate FMO inhibitor, were evaluated and the inhibitory effects of two other important FMO substrates, nicotine and DMXAA, a novel anti‐tumour agent, were investigated.
Multiway Admixture Deconvolution Using Phased or Unphased Ancestral Panels
Authors: Churchhouse Claire , Marchini Jonathan
Published: November 2012

We describe a novel method for inferring the local ancestry of admixed individuals from dense genome‐wide single nucleotide polymorphism data. The method, called MULTIMIX, allows multiple source populations, models population linkage disequilibrium between markers and is applicable to datasets in which the sample and source populations are either phased or unphased. The model is based upon a hidden Markov model of switches in ancestry between consecutive windows of loci. We model the observed haplotypes within each window using a multivariate normal distribution with parameters estimated from the ancestral panels. We present three methods to fit the model—Markov chain Monte Carlo sampling, the Expectation Maximization algorithm, and a Classification Expectation Maximization algorithm. The performance of our method on individuals simulated to be admixed with European and West African ancestry shows it to be comparable to HAPMIX, the ancestry calls of the two methods agreeing at 99.26% of loci across the three parameter groups. In addition to it being faster than HAPMIX, it is also found to perform well over a range of extent of admixture in a simulation involving three ancestral populations. In an analysis of real data, we estimate the contribution of European, West African and Native American ancestry to each locus in the Mexican samples of HapMap, giving estimates of ancestral proportions that are consistent with those previously reported.
Trees Assembling Mann‐Whitney Approach for Detecting Genome‐Wide Joint Association Among Low‐Marginal‐Effect Loci
Authors: Wei Changshuai , Schaid Daniel J. , Lu Qing
Published: November 2012

Common complex diseases are likely influenced by the interplay of hundreds, or even thousands, of genetic variants. Converging evidence shows that genetic variants with low marginal effects (LMEs) play an important role in disease development. Despite their potential significance, discovering LME genetic variants and assessing their joint association on high‐dimensional data (e.g., genome‐wide data) remain a great challenge. To facilitate joint association analysis among a large ensemble of LME genetic variants, we proposed a computationally efficient and powerful approach, which we call Trees Assembling Mann‐Whitney (TAMW). Through simulation studies and an empirical data application, we found that TAMW outperformed multifactor dimensionality reduction (MDR) and the likelihood ratio‐based Mann‐Whitney approach (LRMW) when the underlying complex disease involves multiple LME loci and their interactions. For instance, in a simulation with 20 interacting LME loci, TAMW attained a higher power (power = 0.931) than both MDR (power = 0.599) and LRMW (power = 0.704). In an empirical study of 29 known Crohn's disease (CD) loci, TAMW also identified a stronger joint association with CD than those detected by MDR and LRMW. Finally, we applied TAMW to Wellcome Trust CD GWAS to conduct a genome‐wide analysis. The analysis of 459K single nucleotide polymorphisms was completed in 40 hrs using parallel computing, and revealed a joint association predisposing to CD (P‐value = 2.763 × 10−19). Further analysis of the newly discovered association suggested that 13 genes, such as ATG16L1 and LACC1, may play an important role in CD pathophysiological and etiological processes.
Next day effects of naturalistic alcohol consumption on tasks of attention
Authors: McKinney Adele , Coyle Kieran , Penning Renske , Verster Joris C.
Published: November 2012

Objectives

The aim of this study was to examine the next day effects of alcohol consumption on a range of attention tasks.

Methods

The study followed a counterbalanced repeated measure design, with participants tested the morning following normal/usual alcohol consumption and again the morning after no alcohol consumption. Participants were 48 social drinkers (15 men and 33 women), who performed attention tests at 9 am, 11 am, or 1 pm. Performance was assessed by tasks measuring sustained attention, divided attention, selective attention, and spatial attention and by the Stroop test.

Results

The morning after alcohol consumption, a significantly higher proportion of missed targets was observed (F(1, 40) = 6.43, p < 0.05) in the sustained attention task. In the Stroop test, participants responded significantly slower (F(1, 42) = 8.72, p < 0.005) in the interference condition (when naming the color of the ink of the words) the morning after alcohol consumption. In the selective attention task, the consumption of alcohol the night before eliminated the robust distance by compatibility interaction, which was observed the morning after no alcohol consumption (F(1, 43) = 10.41, p < 0.01). No influence of alcohol was observed in the divided attention test nor in the spatial attention task.

Conclusion

Alcohol consumption has a negative impact on some but not all facets of attentional processing the morning after a normal nights drinking. Copyright © 2012 John Wiley & Sons, Ltd.
The loudness dependence of auditory evoked potentials and effects of psychopathology and psychopharmacotherapy in psychiatric inpatients
Authors: Ostermann Julia , Uhl Idun , Köhler Elke , Juckel Georg , Norra Christine
Published: November 2012

Objective

Many studies have provided evidence for the loudness dependence of auditory evoked potentials (LDAEP) as a marker for central serotonergic activity but remained inconclusive for its suitability in clinical use.

Methods

A cross‐sectional sample of 162 psychiatric inpatients (major depression N = 86, bipolar disorder N = 12, schizophrenia N = 50, and schizoaffective disorder N = 14) and 40 healthy subjects was retrospectively examined for LDAEP and effects of psychopathology and psychopharmacology.

Results

The LDAEP was weaker in patients with affective disorders than in healthy subjects but did not differentiate between the total patient sample and healthy controls. LDAEP correlated significantly with dimensions of the Brief Symptom Inventory in the total patient sample (depression, paranoid ideation, psychoticism, Global Symptom Index, and Positive Symptom Distress Index), in patients with affective disorders (depression) and with schizophrenia spectrum disorders (depression, psychoticism, Global Symptom Index, and Positive Symptom Distress Index). Similar correlations were found in depressed patients with a single noradrenergic and specific serotonergic antidepressant or serotonin–norepinephrine reuptake inhibitor. There was a negative correlation between dosage of typical antipsychotics and LDAEP. Hypnotics generally led to a lower LDAEP.

Conclusion

The LDAEP in patients is related to severity of psychopathologic syndromes irrespective of diagnosis. Chronic psychopharmacologic treatment may also differentially modulate the LDAEP, but longitudinal studies are needed. Copyright © 2012 John Wiley & Sons, Ltd.
Cross‐talk of alpha tocopherol‐associated protein and JNK controls the oxidative stress‐induced apoptosis in prostate cancer cells
Authors: Zhu Baoyi , Li Xiaojuan , Zhang Yuying , Ye Chunwei , Wang Yu , Cai Songwang , Huang Huaiqiu , Cai Yi , Yeh Shuyuan , Huang Zhenhua , Chen Ruihan , Tao Yiran , Wen Xingqiao
Published: November 2012

Excess intracellular reactive oxygen species (ROS) beyond a threshold can induce apoptosis in cancer cells. However, the signal pathways that can augment the proapoptotic function of ROS remain largely unknown. We previously identified a tumor suppressor, alpha‐tocopherol‐associated protein (TAP), yet little is known regarding the role of TAP in the apoptotic signaling in prostate cancer. Interestingly, we recently found that exposure of prostate cancer cells to hydrogen peroxide (H2O2) resulted in induced apoptosis as well as increased expression of TAP. Small interfering RNA (siRNA) mediated silencing of endogenous TAP expression conferred effective protection from H2O2‐induced apoptosis. Further mechanistic study showed exposure of prostate cancer cells to H2O2 resulted in increased phosphorylation of both JNK and c‐Jun, and TAP siRNA effectively decreased H2O2‐induced JNK and c‐Jun phosphorylation. Immunoprecipitation experiments revealed that JNK physically associates with TAP. Furthermore, signaling downstream of JNK to the AP‐1 complex and BH‐3‐only subfamily were found to be regulated on changing the TAP expression status. TAP could also promote the oxidative stress‐induced apoptosis effect of docetaxel. In the mice xenograft model, H2O2 treatment induced TAP expression, JNK phosphorylation and apoptosis of prostate cancer. Recombinant adeno‐associated virus 2 (rAAV2)‐TAP injection significantly sensitizes this H2O2 proapoptotic effect. Together, we have identified a novel functional mechanism that the cross‐talk of TAP‐JNK is involved in oxidative stress‐induced apoptosis in prostate cancer cells. Disrupting the redox balance of cancer cells by this signaling may enable therapeutic selectivity and provide benefit to overcome the drug resistance of prostate cancer.
Peroxisome proliferator‐activated receptor‐γ cofactors in neurodegeneration
Authors: Katsouri Loukia , Blondrath Katrin , Sastre Magdalena
Published: November 2012

Peroxisome proliferator‐activated receptor‐γ (PPARγ) was initially involved in the regulation of glucose and lipid metabolism, cell differentiation, as well as in the transcriptional control of a wide range of inflammatory genes. However, during the last decade, there has been evidence of the implication of this nuclear receptor in neurodegeneration. Various studies have shown that the administration of PPARγ ligands leads to a reduced pathology in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, and stroke. PPARγ cofactors have a critical function in regulating the activity of PPARγ. Recent reports have brought to light the role of the PPARγ coactivator‐1α (PGC‐1α) in several neurodegenerative pathologies. However, very little is know about other PPARγ cofactors in the brain, such as the receptor‐interacting protein 140, as well as the nuclear receptor corepressor, which seems to be required for normal neural development at specific embryonic stages. In this review, we aim to analyze the role of the main regulators of PPARγ in the brain and during neurodegeneration. © 2012 IUBMB IUBMB Life, 64(12): 958–964, 2012
On the moderating role of age in the relationship between pain and cognition
Authors: Oosterman J.M. , Gibson S.J. , Pulles W.L.J.A. , Veldhuijzen D.S.
Published: November 2012

Background

A relationship between pain perception and cognitive function is evident. However, the directionality of this association is unclear and may be influenced by age. That is, inverse associations between pain and cognition have been reported in young and middle‐aged chronic pain patients, whereas higher clinical pain ratings have been associated with better cognitive performance in older chronic pain patients. Therefore, this study examined the possible moderating role of age in the pain‐cognition relationship.

Method

Twenty‐two younger and 24 older chronic pain participants completed neuropsychological tests of psychomotor speed, memory and executive function. They also completed the McGill Pain Questionnaire to evaluate clinical pain.

Results

Interaction analyses revealed that age indeed moderates the relationship between clinical pain ratings and cognitive functions. In the younger age group, pain ratings were inversely related to memory and executive function. In the older age group, a positive relationship was found between pain ratings and executive function, whereas the inverse association of clinical pain with memory was no longer present.

Conclusions

This study was the first to confirm the hypothesis that age is an important moderator of the relationship between pain and cognition. An important finding is that in older adults, most inverse effects of pain on cognition are either no longer present or may even be reversed. The positive relationship between pain and executive function may indicate age‐related reduced integrity of a shared underlying neural substrate.
Neutrophils recruited by CXCR1/2 signalling mediate post‐incisional pain
Authors: Carreira E.U. , Carregaro V. , Teixeira M.M. , Moriconi A. , Aramini A. , Verri W.A. , Ferreira S.H. , Cunha F.Q. , Cunha T.M.
Published: November 2012

Background

Neutrophil recruitment mediated by the CXCL1/KC chemokine and its receptors CXCR1/CXCR2 plays a critical role in inflammatory diseases. Recently, neutrophil migration and activation triggered by CXCL1‐CXCR1/2 signalling was implicated in inflammatory nociception; however, their role in post‐surgical pain has not been elucidated. In this study, we addressed the function of neutrophils in the genesis of post‐incisional pain in an experimental model of post‐surgical pain.

Methods

Mechanical hyperalgesia was determined with an electronic von Frey test in a mouse hindpaw incisional model. Neutrophil accumulation and the level of CXCL1/KC in the plantar tissue were determined by myeloperoxidase activity assay and enzyme‐linked immunosorbent assay, respectively.

Results

An incision in the mouse hindpaw produces long‐lasting mechanical hyperalgesia that persists for at least 72 h after surgery. Following surgery, there was an increase in both neutrophil accumulation and the CXCL1/KC level in the incised paws. The depletion of the mouse neutrophils by vinblastine sulphate or anti‐neutrophil antibody treatments reduced the mechanical hyperalgesia after paw incision. Furthermore, the treatment of mice with ladarixin, an orally acting CXCR1/2 antagonist, also reduced both the mechanical hyperalgesia and the infiltration of neutrophils in the incised paws.

Conclusion

In conclusion, it appears that after surgical processes, neutrophils are recruited by CXCL1‐CXCR1/2 signalling and participate in the cascade of events, leading to mechanical hyperalgesia. These results suggest that blocking neutrophil migration through the inhibition of CXCL1‐CXCR1/2 signalling might be a target to control post‐surgical pain.
Creating Spaces for Black Adolescent Girls to “Write It Out!”
Authors: Muhammad Gholnecsar E.
Published: November 2012

Identity and literacy development are two critical processes shaping the life trajectories of adolescents. Identity development in particular can present unique issues for Black adolescent girls, who are positioned in ways to negotiate their identity(ies) when presented with hegemonic language and representations of what is beauty and what is “Black.” Writing becomes a key literacy practice for Black adolescent girls to make meaning of their identity(ies). Although there are a growing number of studies on literacy and identity development of Black adolescent girls, few studies address writing. A single case study is conducted with a Black adolescent girl who struggles with selfhood to explore how she makes meaning of her identity through writing. She discusses writing within a Black adolescent female summer writing institute juxtaposed with school classrooms. Writing within the summer institute afforded opportunities for her to self‐exert selfhood, while in‐school writing assignments offer little opportunities for self‐expression.
Tensions in Teaching Adolescence/ts: Analyzing Resistances In A Young Adult Literature Course
Authors: Sarigianides Sophia Tatiana
Published: November 2012

Identifying English Education courses focused on young adult literature as apposite sites for exploring teacher conceptions of youth and the texts aimed for youths’ consumptions, this article addresses the multiple sources of tension—and pedagogical potential—of teaching a young adult literature course centrally framed around controversial discourses of adolescence. Reflecting on six years of teaching the course at two different institutions with a strong focus on critical perspectives of youth, the article examines why students in the class would understandably strain against this curriculum, as well as what it might mean for secondary literacy curricula and secondary students if teacher educators and secondary teachers take up these pedagogical risks and sources of resistance in efforts to interrupt dominant and stereotypical discourses about youth.