bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic structures of silicon nanoribbons
Authors: Ding Yi , Ni Jun
Published: August 2009

Using first principles calculations, we investigate the electronic properties of silicon nanoribbons (SiNRs). We find that the armchair SiNRs can be metals or semiconductors depending on width. For the zigzag SiNRs, the antiferromagnetic semiconducting state is the most stable one. Under transverse electric field, the zigzag SiNRs become half-metals. These results show that SiNRs have both rich electronic and magnetic properties with potential applications in silicon-based electronic and spintronic nanodevices.
Structure and phase transitions of monolayers of intermediate-length n-alkanes on graphite studied by neutron diffraction and molecular dynamics simulation
Authors: Diama A. , Matthies B. , Herwig K. W. , Hansen F. Y. , Criswell L. , Mo H. , Bai M. , Taub H.
Published: August 2009

We present evidence from neutron diffraction measurements and molecular dynamics (MD) simulations of three different monolayer phases of the intermediate-length alkanes tetracosane (n-C24H50 denoted as C24) and dotriacontane (n-C32H66 denoted as C32) adsorbed on a graphite basal-plane surface. Our measurements indicate that the two monolayer films differ principally in the transition temperatures between phases. At the lowest temperatures, both C24 and C32 form a crystalline monolayer phase with a rectangular-centered (RC) structure. The two sublattices of the RC structure each consists of parallel rows of molecules in their all-trans conformation aligned with their long axis parallel to the surface and forming so-called lamellas of width approximately equal to the all-trans length of the molecule. The RC structure is uniaxially commensurate with the graphite surface in its [110] direction such that the distance between molecular rows in a lamella is 4.26 Å=3ag, where ag=2.46 Å is the lattice constant of the graphite basal plane. Molecules in adjacent rows of a lamella alternate in orientation between the carbon skeletal plane being parallel and perpendicular to the graphite surface. Upon heating, the crystalline monolayers transform to a “smectic” phase in which the inter-row spacing within a lamella expands by ∼10% and the molecules are predominantly oriented with the carbon skeletal plane parallel to the graphite surface. In the smectic phase, the MD simulations show evidence of broadening of the lamella boundaries as a result of molecules diffusing parallel to their long axis. At still higher temperatures, they indicate that the introduction of gauche defects into the alkane chains drives a melting transition to a monolayer fluid phase as reported previously.
Modeling lattice expansion and cohesive energy of nanostructured materials
Authors: Zhu Y. F. , Zheng W. T. , Jiang Q.
Published: August 2009

The lattice constants and cohesive energies of nanostructured materials (NSs) are modeled using a hard-sphere approach and the model for size-dependent interface energy. The lattice constant of NSs will expand opposite to that of nanoparticles (NPs) as the grain size of NSs and the diameter of NPs decrease. Associated with it, the cohesive energies increase in both cases. However, the increment is less obvious for NSs because the bond deficit at grain boundaries is smaller than that at surfaces. The predictions agree fairly well with the available experimental or computer simulation results of nanostructured metals and semiconductors.
On the calculation of general response properties in subsystem density functional theory
Authors: Neugebauer Johannes
Published: August 2009

A recently developed subsystem formalism within time-dependent density functional theory for excitation energies [J. Chem. Phys. 126, 134116 (2007)] is extended to the calculation of general response properties such as frequency-dependent polarizabilities or optical rotatory dispersion. Furthermore, explicit expressions for oscillator and rotatory strengths are presented. Polarizabilities and optical rotation tensors of the combined system are obtained as the sum of subsystem properties, so that a natural partitioning of the polarizability or the optical rotation is facilitated. This is of great advantage for the analysis of environmental effects on molecular response properties as it allows one to distinguish changes in the ground-state electronic structure of the subsystems from cooperative excited-state effects. A computational scheme that implements the formalism is presented together with applications highlighting the differences between embedding effects included in the subsystem potential and environmental response effects. The method avoids basis-set superposition errors in the calculation of response properties of large molecules, which occur in supermolecular calculations. Possible approximations to the full response algorithm are discussed.
Explicitly correlated second-order Møller–Plesset perturbation theory for unrestricted Hartree–Fock reference functions with exact satisfaction of cusp conditions
Authors: Bokhan Denis , Bernadotte Stephan , Ten-no Seiichiro
Published: August 2009

We formulated and implemented explicitly correlated second-order Møller–Plesset perturbation theory for unrestricted Hartree–Fock reference functions with exact satisfaction of the cusp conditions. For this purpose the geminal basis was augmented by spin-flipped functions. Numerical tests for the correlation energies of several open shell systems have shown faster convergence toward the complete basis set limit when the spin-flipped geminals are included. We also performed benchmark calculations of atomization energies for a set of 16 molecules.
Comment on “Study of geometrical effects on the characteristics of metallic double-walled carbon nanotube waveguides through quantum hydrodynamics” [Phys. Plasmas 16, 063501 (2009)]
Authors: Moradi Afshin , Khosravi Heidar
Published: August 2009

In a recent article [Y. Ahmadizadeh, C. Javaherian, and B. Shokri, Phys. Plasmas 16, 063501 (2009)], Shokri and co-workers studied the propagation of a plasma wave in the double-walled carbon nanotubes. Here we show that their paper is largely a copy of our work [A. Moradi and H. Khosravi, Phys. Lett. A 371, 1 (2007)] and also that no reference was made to our paper.
Thermoelectric power generator module of 16×16 Bi2Te3 and 0.6% ErAs:(InGaAs)1−x(InAlAs)x segmented elements
Authors: Zeng Gehong , Bahk Je-Hyeong , Bowers John E. , Lu Hong , Gossard Arthur C. , Singer Suzanne L. , Majumdar Arun , Bian Zhixi , Zebarjadi Mona , Shakouri Ali
Published: August 2009

We report the fabrication and characterization of thermoelectric power generator modules of 16×16 segmented elements consisting of 0.8 mm thick Bi2Te3 and 50 μm thick ErAs:(InGaAs)1−x(InAlAs)x with 0.6% ErAs by volume. An output power up to 6.3 W was measured when the heat source temperature was at 610 K. The thermoelectric properties of (InGaAs)1−x(InAlAs)x were characterized from 300 up to 830 K. The finite element modeling shows that the performance of the generator modules can further be enhanced by improving the thermoelectric properties of the element materials, and reducing the electrical and thermal parasitic losses.
Self-cleaning and surface recovery with arsine pretreatment in ex situ atomic-layer-deposition of Al2O3 on GaAs
Authors: Cheng Cheng-Wei , Hennessy John , Antoniadis Dimitri , Fitzgerald Eugene A.
Published: August 2009

Annealing native oxide covered GaAs samples in Arsine(AsH3) prior to atomic-layer-deposition of Al2O3 with trimethyaluminum (TMA) and isopropanol (IPA) results in capacitance-voltage (C-V) characteristics of the treated samples that resemble the superior C-V characteristics of p-type GaAs grown by an in situ metal-organic chemical vapor deposition process. Both TMA and IPA show self-cleaning effect on removing the native oxide in ex situ process, little evidence of a native oxide was observed with high resolution transmission electron microscopy at the Al2O3/GaAs interface. The discrepancy in the C-V characteristics was observed in in situ p- and n-type GaAs samples.
Microwave-assisted magnetization reversal in a Co/Pd multilayer with perpendicular magnetic anisotropy
Authors: Nozaki Yukio , Narita Naoyuki , Tanaka Terumitsu , Matsuyama Kimihide
Published: August 2009

Microwave-assisted magnetization reversal in a rectangle of a Co/Pd multilayer with a perpendicular magnetic anisotropy is examined using vector network analyzer ferromagnetic resonance (FMR) spectroscopy. A microwave field is applied along the in-plane direction of the rectangle together with a negative dc easy-axis field smaller than the coercive field. Broadening or splitting of the peak profile in the FMR spectrum suggesting the formation of multidomain structure appears after the microwave field is applied. The dominance of microwave-assisted nucleation of magnetization is supported by the frequency dependence of the probability with which the multidomain structure appears.
Strain balanced InAs/InAsSb superlattice structures with optical emission to 10 μm
Authors: Lackner D. , Pitts O. J. , Steger M. , Yang A. , Thewalt M. L. W. , Watkins S. P.
Published: August 2009

We report the growth and optical characterization of InAsSb/InAs strain balanced superlattice structures on GaSb substrates for potential application in midinfrared photodetectors. Photoluminescence (PL) emission was observed in the range 5 μm≤λ≤10 μm at 4 K for Sb compositions 0.14≤xSb≤0.27. The PL energy was found to depend approximately linearly on antimony, consistent with a type II band lineup. The dependence of the emission energies on the Sb mole fraction is in agreement with trends predicted by various theoretical works. The data suggest that this transition reaches zero energy for a composition of xSb=0.37.
Numerical calculations demonstrating complete stabilization of the ideal magnetohydrodynamic resistive wall mode by longitudinal flow
Authors: Smith S. P. , Jardin S. C. , Freidberg J. P. , Guazzotto L.
Published: August 2009

The cylindrical ideal magnetohydrodynamic (MHD) stability problem, including flow and a resistive wall, is cast in the standard mathematical form, ωA⋅x=B⋅x, without discretizing the vacuum regions surrounding the plasma. This is accomplished by means of a finite element expansion for the plasma perturbations, by coupling the plasma surface perturbations to the resistive wall using a Green’s function approach, and by expanding the unknown vector, x, to include the perturbed current in the resistive wall as an additional degree of freedom. The ideal MHD resistive wall mode (RWM) can be stabilized when the plasma has a uniform equilibrium flow such that the RWM frequency resonates with the plasma’s Doppler-shifted sound continuum modes. The resonance induces a singularity in the parallel component of the plasma perturbations, which must be adequately resolved. Complete stabilization within the ideal MHD model (i.e., without parallel damping being added) is achieved as the grid spacing in the region of the resonance is extrapolated to 0 step size.
Foraminifera promote calcification by elevating their intracellular pH
Authors: de Nooijer Lennart Jan , Toyofuku Takashi , Kitazato Hiroshi
Published: August 2009

Surface seawaters are supersaturated with respect to calcite, but high concentrations of magnesium prevent spontaneous nucleation and growth of crystals. Foraminifera are the most widespread group of calcifying organisms and generally produce calcite with a low Mg content, indicating that they actively remove Mg
2+
from vacuolized seawater before calcite precipitation. However, one order of foraminifera has evolved a calcification pathway, by which it produces calcite with a very high Mg content, suggesting that these species do not alter the Mg/Ca ratio of vacuolized seawater considerably. The cellular mechanism that makes it possible to precipitate calcite at high Mg concentrations, however, has remained unknown. Here we demonstrate that they are able to elevate the pH at the site of calcification by at least one unit above seawater pH and, thereby, overcome precipitation-inhibition at ambient Mg concentrations. A similar result was obtained for species that precipitate calcite with a low Mg concentration, suggesting that elevating the pH at the site of calcification is a widespread strategy among foraminifera to promote calcite precipitation. Since the common ancestor of these two groups dates back to the Cambrian, our results would imply that this physiological mechanism has evolved over half a billion years ago. Since foraminifera rely on elevating the intracellular pH for their calcification, our results show that ongoing ocean acidification can result in a decrease of calcite production by these abundant calcifyers.
Modeling early retinal development with human embryonic and induced pluripotent stem cells
Authors: Meyer Jason S. , Shearer Rebecca L. , Capowski Elizabeth E. , Wright Lynda S. , Wallace Kyle A. , McMillan Erin L. , Zhang Su-Chun , Gamm David M.
Published: August 2009

Human pluripotent stem cells have the potential to provide comprehensive model systems for the earliest stages of human ontogenesis. To serve in this capacity, these cells must undergo a targeted, stepwise differentiation process that follows a normal developmental timeline. Here we demonstrate the ability of both human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells to meet these requirements for human retinogenesis. Upon differentiation, hESCs initially yielded a highly enriched population of early eye field cells. Thereafter, a subset of cells acquired features of advancing retinal differentiation in a sequence and time course that mimicked in vivo human retinal development. Application of this culture method to a human iPS cell line also generated retina-specific cell types at comparable times in vitro. Lastly, altering endogenous signaling during differentiation affected lineage-specific gene expression in a manner consistent with established mechanisms of early neural and retinal cell fate determination. These findings should aid in the investigation of the molecular events governing retinal specification from human pluripotent stem cells.
Weight gain restriction during pregnancy is safe for both the mother and neonate
Authors: CLAESSON ING‐MARIE , BRYNHILDSEN JAN , CEDERGREN MARIE , JEPPSSON ANNIKA , SYDSJÖ ADAM , JOSEFSSON ANN
Published: August 2009

The objective of this study was to investigate whether pregnancy, delivery, and neonatal outcome among obese pregnant women who took part in an intervention study for weight restriction differed from a group of obese pregnant women attending regular antenatal care. The intervention group consisted of 155 obese pregnant women and 193 obese pregnant women who formed a control group. We found that a weight gain restriction of less than 7 kg during pregnancy is safe for both the mother and the neonate.
Young people on the margins: In need of more choices and more chances in twenty‐first century Scotland
Authors: Finlay Ian , Sheridan Marion , McKay Jane , Nudzor Hope
Published: August 2009

The aim of this study was to find out more about the lives of young people in the category ‘not in education, employment or training’ (NEET). We worked intensively with 26 young people in four smaller groups, spending three days with each group. During our time with them we engaged in a variety of creative and artistic activities designed to help them to construct accounts of their lives for us with the purpose of gaining an understanding of what it was like to be NEET. Three significant issues that emerged from these life stories are discussed in this paper. These are the problematic nature of the discourse of NEET sub‐groups; the challenges of school‐exclusion policies and practices; and the myth of low aspirations.
Using a mutual information-based site transition network to map the genetic evolution of influenza A/H3N2 virus
Authors: Xia Zhen , Jin Gulei , Zhu Jun , Zhou Ruhong
Published: August 2009

Motivation: Mapping the antigenic and genetic evolution pathways of influenza A is of critical importance in the vaccine development and drug design of influenza virus. In this article, we have analyzed more than 4000 A/H3N2 hemagglutinin (HA) sequences from 1968 to 2008 to model the evolutionary path of the influenza virus, which allows us to predict its future potential drifts with specific mutations.

Results: The mutual information (MI) method was used to design a site transition network (STN) for each amino acid site in the A/H3N2 HA sequence. The STN network indicates that most of the dynamic interactions are positioned around the epitopes and the receptor binding domain regions, with strong preferences in both the mutation sites and amino acid types being mutated to. The network also shows that antigenic changes accumulate over time, with occasional large changes due to multiple co-occurring mutations at antigenic sites. Furthermore, the cluster analysis by subdividing the STN into several subnetworks reveals a more detailed view about the features of the antigenic change: the characteristic inner sites and the connecting inter-subnetwork sites are both responsible for the drifts. A novel five-step prediction algorithm based on the STN shows a reasonable accuracy in reproducing historical HA mutations. For example, our method can reproduce the 2003–2004 A/H3N2 mutations with ∼70% accuracy. The method also predicts seven possible mutations for the next antigenic drift in the coming 2009–2010 season. The STN approach also agrees well with the phylogenetic tree and antigenic maps based on HA inhibition assays.

Availability: All code and data are available at http://ibi.zju.edu.cn/birdflu/

Contact:  ruhongz@us.ibm.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Learning gene regulatory networks from gene expression measurements using non-parametric molecular kinetics
Authors: Äijö Tarmo , Lähdesmäki Harri
Published: August 2009

Motivation: Regulation of gene expression is fundamental to the operation of a cell. Revealing the structure and dynamics of a gene regulatory network (GRN) is of great interest and represents a considerably challenging computational problem. The GRN estimation problem is complicated by the fact that the number of gene expression measurements is typically extremely small when compared with the dimension of the biological system. Further, because the gene regulation process is intrinsically complex, commonly used parametric models can provide too simple description of the underlying phenomena and, thus, can be unreliable. In this article, we propose a novel methodology for the inference of GRNs from time-series and steady-state gene expression measurements. The presented framework is based on the use of Bayesian analysis with ordinary differential equations (ODEs) and non-parametric Gaussian process modeling for the transcriptional-level regulation.

Results: The performance of the proposed structure inference method is evaluated using a recently published in vivo dataset. By comparing the obtained results with those of existing ODE- and Bayesian-based inference methods we demonstrate that the proposed method provides more accurate network structure learning. The predictive capabilities of the method are examined by splitting the dataset into a training set and a test set and by predicting the test set based on the training set.

Availability: A MATLAB implementation of the method will be available from http://www.cs.tut.fi/~aijo2/gp upon publication

Contact:  harri.lahdesmaki@tut.fi

Supplementary information:  Supplementary data are available at Bioinformatics online.
digeR: a graphical user interface R package for analyzing 2D-DIGE data
Authors: Fan Yue , Murphy T. Brendan , Watson R. William G.
Published: August 2009

Summary: 2D Difference In-Gel Electrophoresis (2D-DIGE) or 2D gel technology is being used as a routine proteomics technique for biomarker discovery. Analyzing such high-dimensional data requires multivariate analysis techniques to be applied. In addition, protein post-translational modification (PTM) information from the 2D gel data is usually overlooked. We report on an R package, digeR, with an easy to use graphical user interface for analyzing 2D-DIGE (2D gel) data. It provides a tool for visually looking for potential PTM changes from different biological states and support biomarker discovery through multivariate analysis techniques.

Availability: digeR package is freely available from the CRAN: http://cran.r-project.org/web/packages/digeR/index.html.

Contact:  yue.fan@ucd.ie

Supplementary information:  Supplementary data are available at Bioinformatics online.
Human Papillomavirus, Genital Warts and Vaccination
Authors: Pye Laura
Published: August 2009

Genital warts (condyloma acuminata) are caused by the human papillomavirus (HPV) and are the most frequently diagnosed viral sexually transmitted infection in the UK. This article aims to provide an overview of the natural history of HPV, the clinical presentation and management of genital warts and an overview of the national HPV vaccination programme.
Mobility Impairment in Older Adults
Authors: O'Hanlon Shane , Twomey Cillian
Published: August 2009

Older adults often present to their general practitioner with mobility impairment. Finding the cause can be a challenging process. This article discusses the assessment and investigation of deterioration in mobility in older adults.
Portfolios and Personal Development Plans
Authors: Shiner Alice
Published: August 2009

The ePortfolio—love it or loathe it—is an integral part of the workplace-based assessment, it is now a fact of life for general practice trainees. It is also preparation for the appraisal system for qualified GPs, which is heavily reliant upon portfolios of evidence and the creation of personal development plans (or PDPs). Such reliance is only likely to increase with the proposed new revalidation system, which is currently expected to be introduced in 2010–11. Given this context, it is wise for GP trainees to learn how to use these tools to best effect, not only to provide robust evidence of good practice but also to aid personal development. This article aims to describe the way in which PDPs and portfolios can be best employed during your years as a trainee, equipping you with useful skills for a career in general practice. Although the use of tools such as significant event analysis, audit and the consultation observation tool (COT) and case-based discussion, assessments are all important reflective components of the ePortfolio, they will not be discussed in depth in this article.
Vaginal Discharge
Authors: Seepana Sreekala , Allamsetty Sudhakar
Published: August 2009

Vaginal discharge is a common presenting symptom encountered in day-to-day practice. From the time of puberty, the vagina is colonized by lactobacilli and other bacteria. Commensal lactobacilli metabolize glycogen in the vaginal epithelium to produce lactic acid, maintaining an acidic environment in the vagina (pH less than 4.5) and providing defence against infection.
Peripheral Neuropathy
Authors: Simon Chantal
Published: August 2009

Peripheral neuropathy is defined as dysfunction of the structure and function of peripheral motor, sensory and autonomic nerves. Although many individual causes of peripheral neuropathy are rare, it is estimated that up to 8% of the population have some degree of peripheral neuropathy or a total of 4.7 million people in the UK alone. There are many different types of peripheral neuropathy but the most common cause is diabetes and up to 60% of diabetic patients have a peripheral neuropathy of some sort. Peripheral neuropathy not only causes problems with everyday functioning but also in many cases causes severe, disabling neuropathic pain. This article aims to provide a simple overview of peripheral neuropathy and its management in primary care.
Simultaneous but not independent anisomycin infusions in insular cortex and amygdala hinder stabilization of taste memory when updated
Authors: García-DeLaTorre Paola , Rodriguez-Ortiz Carlos J. , Arreguin-Martinez Jose L. , Cruz-Castañeda Paulina , Bermúdez-Rattoni Federico
Published: August 2009

Reconsolidation has been described as a process where a consolidated memory returns to a labile state when retrieved. Growing evidence suggests that reconsolidation is, in fact, a destabilization/stabilization process that incorporates updated information to a previously consolidated memory. We used the conditioned taste aversion (CTA) task in order to test this theory. On the first trial, the conditioned stimulus (CS) (saccharin) was associated to the unconditioned stimulus (US) (LiCl injection), and as a result, aversion to saccharin was obtained. The following day, animals were injected with anisomycin in either the insular cortex (IC), central amygdala (CeA), basolateral amygdala (BLA), or simultaneously in IC and CeA or IC and BLA, and a second CTA trial was carried out in which updated information was acquired. Animals were tested 24 h later. When protein synthesis was inhibited in either the IC or CeA, consolidation was affected and previously consolidated memory was unimpaired. However, when both the IC and CeA were simultaneously anisomycin injected, the previously consolidated memory was affected. After repeated association trials, protein synthesis inhibition in the IC and CeA did not have an effect on taste memory. These results suggest that the IC and the CeA are necessary for taste-aversion consolidation, and that both share the previously consolidated memory trace. In addition, our data demonstrated that protein synthesis in either the IC or the CeA suffices to stabilize previously consolidated taste memory when destabilized by incorporation of updated information.
Role of dentate gyrus in aligning internal spatial map to external landmark
Authors: Won Lee Jong , Kim Woon Ryoung , Sun Woong , Jung Min Whan
Published: August 2009

Humans and animals form internal representations of external space based on their own body movement (dead reckoning) as well as external landmarks. It is poorly understood, however, how different types of information are integrated to form a unified representation of external space. To examine the role of dentate gyrus (DG) in this process, we conducted physiological and behavioral experiments using Bax knockout (Bax-KO) mice in which newly generated granule cells continue to accumulate disrupting neural circuitry specifically in the DG. Unlike in wild-type (WT) littermates, spatial firing of hippocampal neurons was completely dissociated from a distinct visual cue and instead, tended to stay constant relative to the recording room in Bax-KO mice. Behaviorally, whereas spatial learning was intact in conventional spatial reference memory tasks, Bax-KO mice were impaired in finding a target location based on visual landmarks when target locations predicted by dead reckoning and visual landmarks were made incongruent. These results provide converging evidence for the role of DG in binding animal's internal spatial map with the sensory information on external landmarks in building a distinct spatial representation for each environment.
Reduced false memory after sleep
Authors: Fenn Kimberly M. , Gallo David A. , Margoliash Daniel , Roediger Henry L. , Nusbaum Howard C.
Published: August 2009

Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False recognition of nonstudied words was reduced after sleep, relative to an equal retention interval of wakefulness, with no change in correct recognition of studied words. These experiments are the first to show that false memories can be reduced following sleep, and they extend the benefits of sleep to include increased accuracy of episodic memory.
Transcript Profiling Provides Evidence of Functional Divergence and Expression Networks among Ribosomal Protein Gene Paralogs inBrassica napus
Authors: Whittle Carrie A. , Krochko Joan E.
Published: August 2009

The plant ribosome is composed of 80 distinct ribosomal (r)-proteins. In Arabidopsis thaliana, each r-protein is encoded by two or more highly similar paralogous genes, although only one copy of each r-protein is incorporated into the ribosome. Brassica napus is especially suited to the comparative study of r-protein gene paralogs due to its documented history of genome duplication as well as the recent availability of large EST data sets. We have identified 996 putative r-protein genes spanning 79 distinct r-proteins in B. napus using EST data from 16 tissue collections. A total of 23,408 tissue-specific r-protein ESTs are associated with this gene set. Comparative analysis of the transcript levels for these unigenes reveals that a large fraction of r-protein genes are differentially expressed and that the number of paralogs expressed for each r-protein varies extensively with tissue type in B. napus. In addition, in many cases the paralogous genes for a specific r-protein are not transcribed in concert and have highly contrasting expression patterns among tissues. Thus, each tissue examined has a novel r-protein transcript population. Furthermore, hierarchical clustering reveals that particular paralogs for nonhomologous r-protein genes cluster together, suggesting that r-protein paralog combinations are associated with specific tissues in B. napus and, thus, may contribute to tissue differentiation and/or specialization. Altogether, the data suggest that duplicated r-protein genes undergo functional divergence into highly specialized paralogs and coexpression networks and that, similar to recent reports for yeast, these are likely actively involved in differentiation, development, and/or tissue-specific processes.
Different histological types of non‐small cell lung cancer have distinct folate and DNA methylation levels
Authors: Jin MingJi , Kawakami Kazuyuki , Fukui Yousuke , Tsukioka Sayaka , Oda Makoto , Watanabe Go , Takechi Teiji , Oka Toshinori , Minamoto Toshinari
Published: August 2009

Aberrant DNA methylation is a commonly observed epigenetic change in lung cancer. Folate has been suggested to play a role in the homeostasis of DNA methylation and has also been implicated in cancer chemotherapy. We investigated a possible role for folate in DNA methylation by measuring folate concentrations in tumors and adjacent normal tissues from 72 non‐small cell lung cancer (NSCLC) patients. These were compared to DNA methylation levels and to clinicopathological features. Folate concentrations were determined as the sum of 5,10‐methylenetetrahydrofolate and tetrahydrofolate. The MethyLight assay was used to quantitate methylation in promoter regions of P16(CDKN2A), APC, CDH13, RARB, RASSF1, RUNX3, and MYOD1. Methylation of LINE‐1 repeats was used as a surrogate for global methylation. Folate levels in tumors correlated positively with LINE‐1, CDH13, and RUNX3 methylation. Folate concentrations and methylation of LINE‐1, RASSF1, and RUNX3 were significantly higher in adenocarcinoma compared to squamous cell carcinoma (SCC). Two sets of array‐based data retrieved from the Gene Expression Omnibus consistently showed that expression of FOLR1, a folate transport enzyme, and GGH, an enzyme that prevents folate retention, were higher and lower, respectively, in adenocarcinomas compared to SCC. This was independently validated by quantitative RT‐PCR in 26 adenocarcinomas and 13 SCC. Our results suggest that folate metabolism plays a role in aberrant DNA methylation in NSCLC. The histological subtype differences in folate concentration and DNA methylation observed here were associated with distinct expression patterns for folate metabolizing enzymes. These findings may have clinical applications for histology‐directed chemotherapy with fluoropyrimidine and anti‐folates in NSCLC. (Cancer Sci 2009l; 100: 2325–2330)
Roles of a prostaglandin E‐type receptor, EP3, in upregulation of matrix metalloproteinase‐9 and vascular endothelial growth factor during enhancement of tumor metastasis
Authors: Amano Hideki , Ito Yoshiya , Suzuki Tastunori , Kato Shintaro , Matsui Yoshio , Ogawa Fumihiro , Murata Takahiko , Sugimoto Yukihiko , Senior Robert , Kitasato Hidero , Hayashi Izumi , Satoh Yukitoshi , Narumiya Shuh , Majima Masataka
Published: August 2009

Cyclooxygenase (COX)‐2 is known to correlate with poor cancer prognosis and to contribute to tumor metastasis. However, the precise mechanism of this phenomenon remains unknown. We have previously reported that host stromal prostaglandin E2 (PGE2)–prostaglandin E2 receptor (EP)3 signaling appears critical for tumor‐associated angiogenesis and tumor growth. Here we tested whether the EP3 receptor has a critical role in tumor metastasis. Lewis lung carcinoma (LLC) cells were intravenously injected into WT mice and mice treated with the COX‐2 inhibitor NS‐398. The nonselective COX inhibitor aspirin reduced lung metastasis, but the COX‐1 inhibitor SC560 did not. The expression of matrix metalloproteinases (MMP)‐9 and vascular endothelial growth factor (VEGF)‐A was suppressed in NS‐398‐treated mice compared with PBS‐treated mice. Lungs containing LLC colonies were markedly reduced in EP3 receptor knockout (EP3−/−) mice compared with WT mice. The expression of MMP‐9 and VEGF‐A was downregulated in metastatic lungs of EP3−/− mice. An immunohistochemical study revealed that MMP‐9‐expressing endothelial cells were markedly reduced in EP3−/− mice compared with WT mice. When HUVEC were treated with agonists for EP1, EP2, EP3, or EP4, only the EP3 agonist enhanced MMP‐9 expression. These results suggested that EP3 receptor signaling on endothelial cells is essential for the MMP‐9 upregulation that enhances tumor metastasis and angiogenesis. An EP3 receptor antagonist may be useful to protect against tumor metastasis. (Cancer Sci 2009; 100: 2318–2324)
Enhanced delivery of macromolecular antitumor drugs to tumors by nitroglycerin application
Authors: Seki Takahiro , Fang Jun , Maeda Hiroshi
Published: August 2009

Dose regimens of anticancer agents are usually designed on the basis of the maximum tolerable drug doses, and toxicity prevents drug usage at higher doses, even though the drugs may be more effective at the higher doses. We previously studied macromolecular anticancer drugs, i.e. those larger than 40 kDa, and observed their accelerated accumulation in tumors. Their concentration in tumors was more than 5–100‐fold their blood concentration because of the enhanced permeability and retention (EPR) effect. Here, we report that the EPR effect was enhanced by applying nitroglycerin (NG) ointment on the skin of tumor‐bearing animals. Tumors studied included breast cancer, which was induced in Sprague–Dawley rats by the chemical carcinogen 7,12‐dimethylbenz[a]anthracene, and three different transplanted tumor models in mice. NG was applied on tumor or nontumorous normal skin as well. Two to three times more putative macromolecular drug (an Evans blue/albumin complex) was delivered to solid tumors with NG than without NG. We also demonstrated that NG enhanced tumor delivery with another macromolecular drug candidate, PZP, i.e. polyethylene glycol‐conjugated zinc protoporphyrin IX, which inhibits heme oxygenase‐1. In addition, we investigated the therapeutic effect of NG using a combination with low molecular weight anthracycline or high molecular weight PZP in mouse tumor models. NG had no apparent toxicity at the doses used, and showed significantly increased therapeutic effects in both cases. Regardless of its site of application, NG thus enhanced the delivery of the drug to tumors, and enhanced therapeutic effects. (Cancer Sci 2009; 100: 2426–2430)
Identification of serum biomarkers for pancreatic adenocarcinoma by proteomic analysis
Authors: Guo Jinghui , Wang Wenjing , Liao Ping , Lou Wenhui , Ji Yuan , Zhang Chunyan , Wu Jiong , Zhang Shuncai
Published: August 2009

Diagnosis of pancreatic adenocarcinoma (PaCa) at an early stage is important for successful treatment and improving the prognosis of patients. Serum samples were applied to strong anionic exchange chromatography (SAX) protein chips for protein profiling by surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS) to distinguish PaCa from noncancer. The Wilcoxon rank‐sum test, decision tree algorithm, and logistic regression were used to statistically analyze the multiple protein peaks. Sixty‐one protein peaks between 2000 and 30 000 m/z ratios were detected to establish multiple decision classification trees for differentiating the known disease states. A sensitivity of 0.833 and a specificity of 1.000 were obtained in distinguishing PaCa from healthy controls and benign pancreatic diseases. Six protein biomarkers related to different PaCa TNM stages were detected (P < 0.01). One protein biomarker (m/z 4016) rich in PaCa had a down‐regulated trend when preoperative and postoperative samples (P < 0.05) were compared. Three protein biomarkers (m/z 4155, 4791, and 28 068) were detected in the differential diagnosis of the three test groups (P < 0.05). A peak m/z 28 068 was identified as C14orf16 using ProteinChip immunoassay. C14orf166 levels were significantly higher in the serum of patients with PaCa compared with the control group using a sandwich immunoenzymatic system. Immunolabeling of tissue sections revealed that the C14orf166 protein was strongly expressed in tumor cells. The results suggest that SELDI‐TOF‐MS serum profiling is helpful for the diagnostic, prognostic or therapeutic effects of PaCa, which is superior to CA 19‐9. The identified protein biomarker C14orf166 is a potential biomarker of PaCa. (Cancer Sci 2009; 100: 2292–2301)
Engineered anti‐CD20 antibodies with enhanced complement‐activating capacity mediate potent anti‐lymphoma activity
Authors: Natsume Akito , Shimizu‐Yokoyama Yukiko , Satoh Mitsuo , Shitara Kenya , Niwa Rinpei
Published: August 2009

One of the major issues in current antibody therapy is insufficient efficacy. Various biological factors relating to the host’s immune system or tumor cells have been suggested to reduce the efficacy of anti‐CD20 therapy in B‐cell malignancies. In this study, we characterized the in vitro anti‐lymphoma activity of anti‐CD20 antibodies having a novel engineered heavy chain with enhanced complement‐dependent cytotoxicity (CDC). Anti‐CD20 antibodies having a variant heavy constant region of mixed IgG1/IgG3 isotype, which have previously been found to enhance CDC, were investigated for their in vitro CDC against lymphoma cells and whole blood B‐cell depletion activity. Use of the variant constant region greatly increased the CDC of an anti‐CD20 antibody having variable regions identical to those of rituximab to the level shown by an IgG1 antibody of ofatumumab. Although the whole blood assay showed different cytotoxicity patterns among individual blood donors, the CDC‐enhancing variant of rituximab showed higher activity than the parent IgG1 and consistently showed maximized activity when further combined with antibody‐dependent cellular cytotoxicity (ADCC)‐enhancing modification by fucose removal from Fc‐linked oligosaccharides. In addition, the rituximab variant showed potent CDC against transfectant cells with lower CD20 expression and chronic lymphocytic leukemia–derived cell lines with higher complement regulatory proteins. These findings suggest that CDC enhancement, both alone and in combination with ADCC enhancement, increases the anti‐lymphoma activity of anti‐CD20 antibodies irrespective of individual differences in effector functions, and renders current anti‐CD20 therapy capable of overcoming the potential resistance mechanisms. (Cancer Sci 2009; 100: 2411–2418)
The efficacy and safety of a third anti‐TNF monoclonal antibody in Crohn’s disease after failure of two other anti‐TNF antibodies
Authors: ALLEZ M. , VERMEIRE S. , MOZZICONACCI N. , MICHETTI P. , LAHARIE D. , LOUIS E. , BIGARD M.‐A. , HÉBUTERNE X. , TRETON X. , KOHN A. , MARTEAU P. , CORTOT A. , NICHITA C. , VAN ASSCHE G. , RUTGEERTS P. , LÉMANN M. , COLOMBEL J.‐F.
Published: August 2009

Background  Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn’s disease (CD) patients previously treated with infliximab (IFX).

Aim  To assess the efficacy and tolerability of a third anti‐TNF in CD after failure of and/or intolerance to two different anti‐TNF antibodies.

Methods  Crohn’s disease patients who received ADA or CZP after loss of response and/or intolerance to two anti‐TNF agent were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed.

Results  Sixty‐seven patients treated with CZP (n = 40) or ADA (n = 27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow‐up, the third anti‐TNF had been stopped in 36 patients for intolerance (n = 13), or failure (n = 23). Two deaths were observed.

Conclusions  The treatment with a third anti‐TNF (CZP or ADA) agent of CD patients, who have experienced loss of response and/or intolerance to two anti‐TNF antibodies, has favourable short‐term and long‐term efficacy. It is an option to be considered in patients with no other therapeutic options.
Mercaptopurine rescue after azathioprine‐induced liver injury in inflammatory bowel disease
Authors: BERMEJO F. , LÓPEZ‐SANROMÁN A. , ALGABA A. , VAN‐DOMSELAAR M. , GISBERT J. P. , GARCÍA‐GARZÓN S. , GARRIDO E. , PIQUERAS B. , DE LA POZA G. , GUERRA I.
Published: August 2009

Background  Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation.

Aim  To describe the tolerance to mercaptopurine (MP) in patients with previous AZA‐related liver injury.

Methods  Retrospective description of 31 patients (14 Crohn’s, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy.

Results  Mean AZA dose was 2.2 ± 0.4 mg·kg/day. Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1–5.2). The type of AZA‐related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29%. After a median of 2.5 months (0.7–5.2), the therapy was switched to MP at a mean dose of 1.3 ± 0.2 mg·kg/day. Median of follow‐up of MP therapy was 32 months (8–54). In 87.1% of patients (95%CI: 70–96%), MP was tolerated without further liver injury; of these, 77.4% tolerated full MP doses and 9.7% tolerated lower doses. In a further cohort of 12.9% of patients, (95%CI: 3–29%), liver injury reappeared (two cholestasis, two mixed), 1–3 months after the onset of MP exposure.

Conclusion  The administration of MP is a good alternative in patients with AZA‐related liver injury, before thiopurines are definitely discarded.
A novel missense mutation in SLC40A1 results in resistance to hepcidin and confirms the existence of two ferroportin‐associated iron overload diseases
Authors: Létocart Emilie , Le Gac Gérald , Majore Silvia , Ka Chandran , Radio Francesca C. , Gourlaouen Isabelle , De Bernardo Carmelilia , Férec Claude , Grammatico Paola
Published: August 2009

Ferroportin‐related iron overload disease differs from haemochromatosis in that it has a dominant mode of inheritance and is usually associated with macrophage iron sequestration. However, it is thought that mutations with opposite effects on protein functions, i.e. loss‐of‐function versus gain‐of‐function mutations, are responsible for variable phenotype presentations. The present study investigated the functional relevance of a novel ferroportin variant: the c.1502 A>G transition, which changes amino acid 501 from tyrosine to cysteine (p.Y501C). This novel variant was identified in a pedigree originating from Central Italy and, although an intra‐familial phenotype heterogeneity was observed, it co‐segregated with an iron overload picture similar to that of the HFE‐related typical haemochromatosis. In cultured cells, the p.Y501C mutant protein reached the plasma membrane and retained a full iron export ability. By contrast, it was resistant to inhibition by hepcidin. These findings confirm that certain ferroportin mutations compromise the activity of hepcidin in iron homeostasis, mimicking hepcidin deficiency as described in all types of hemochromatosis.
Allogeneic haemopoietic stem cell transplantation in children: what alternative donor should we choose when no matched sibling is available?
Authors: Hough Rachael , Cooper Nicola , Veys Paul
Published: August 2009

Allogeneic haemopoietic stem cell transplantation has provided curative therapy for life‐threatening malignant and non‐malignant diseases in children for over 40 years. Only 25% of children in whom an allograft is indicated have the ideal option of a human leucocyte antigen‐identical sibling donor. Substantial advances in the use of alternative donors (unrelated volunteer donors, haploidentical family donors and unrelated umbilical cord blood donors) now make it possible for almost all children to benefit from this life‐saving treatment. Each donor choice is associated with distinct advantages and disadvantages, which have greater or lesser importance in different diseases. We review the current status of alternative donor transplantation for haematological malignancies, primary immunodeficiencies, inherited metabolic disorders and bone marrow failure syndromes and outline the current UK consensus donor selection algorithms for these disease groups.
Preclinical activity of 8‐chloroadenosine with mantle cell lymphoma: roles of energy depletion and inhibition of DNA and RNA synthesis
Authors: Dennison Jennifer B. , Balakrishnan Kumudha , Gandhi Varsha
Published: August 2009

8‐Chloroadenosine (8‐Cl‐Ado), an RNA‐directed nucleoside analogue, is currently under evaluation in phase I clinical trials for treatment of chronic lymphocytic leukaemia. In the current study, the efficacy of 8‐Cl‐Ado was evaluated using mantle cell lymphoma (MCL) cell lines: Granta 519, JeKo, Mino, and SP‐53. After continuous exposure to 10 μmol/l 8‐Cl‐Ado for 24 h, loss of mitochondrial transmembrane potential and poly [adenosine diphosphate (ADP)‐ribose] polymerase (PARP) cleavage were detected in three of four cell lines. Reduced ATP levels (30–60% reduction) and concurrent 8‐Cl‐ATP accumulation were highly associated with cell death (P < 0·01). The intracellular 8‐Cl‐ATP concentrations were also highly correlated with inhibition of global transcription (50–90%, r2 = 0·90, P < 0·01). However, the inhibition of transcription only accounted for 30–40% of cell death as determined by equivalent inhibition with actinomycin D. Likewise, short‐lived mRNAs, those encoding cyclin D1 and Mcl‐1, were not consistently reduced after treatment. Unique to MCL as compared to other haematological malignancies, 8‐Cl‐Ado inhibited the rates of DNA synthesis and selectively depleted dATP pools (50–80%). We conclude that the DNA and RNA directed actions of 8‐Cl‐Ado in combination with depleted energetics may promote cell death and inhibit growth of MCL cell lines.