bluuebunny/crossref_metadata_2025 huggingface dataset:
An embedded statistical method for coupling molecular dynamics and finite element analyses
Authors: Saether E. , Yamakov V. , Glaessgen E. H.
Published: January 2009

The coupling of molecular dynamics (MD) simulations with finite element methods (FEM) yields computationally efficient models that link fundamental material processes at the atomistic level with continuum field responses at higher length scales. The theoretical challenge involves developing a seamless connection along an interface between two inherently different simulation frameworks. Various specialized methods have been developed to solve particular classes of problems. Many of these methods link the kinematics of individual MD atoms with finite element (FE) nodes at their common interface, necessarily requiring that the FE mesh be refined to atomic resolution. Some of these coupling approaches also require simulations to be carried out at 0 K and restrict modelling to two‐dimensional material domains due to difficulties in simulating full three‐dimensional material processes. In the present work, a new approach to MD–FEM coupling is developed based on a restatement of the standard boundary value problem used to define a coupled domain. The method replaces a direct linkage of individual MD atoms and FE nodes with a statistical averaging of atomistic displacements in local atomic volumes associated with each FE node in an interface region. The FEM and MD computational systems are effectively independent and communicate only through an iterative update of their boundary conditions. Thus, the method lends itself for use with any FEM or MD code. With the use of statistical averages of the atomistic quantities to couple the two computational schemes, the developed approach is referred to as an embedded statistical coupling method (ESCM). ESCM provides an enhanced coupling methodology that is inherently applicable to three‐dimensional domains, avoids discretization of the continuum model to atomic scale resolution, and permits finite temperature states to be applied. Published in 2009 by John Wiley & Sons, Ltd.
Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis
Authors: Sastre‐Garau Xavier , Peter Martine , Avril Marie‐Françoise , Laude Hélène , Couturier Jérôme , Rozenberg Flore , Almeida Anna , Boitier Françoise , Carlotti Agnès , Couturaud Benoıt , Dupin Nicolas
Published: January 2009

Merkel cell carcinoma (MCC), a skin tumour with neuroendocrine features, was recently found to be associated with a new type of human polyomavirus, called Merkel cell virus (MCV). We investigated the specificity of this association as well as a causal role of MCV in oncogenesis. DNA and RNA from ten cases of MCC were analysed using PCR and RT‐PCR. DNA from 1241 specimens of a wide range of human tumours was also analysed. The DIPS technique was used to identify the integration locus of viral DNA sequences. Array CGH was performed to analyse structural alterations of the cell genome. MCV DNA sequences were found in all ten cases of MCC and in none of the 1241 specimens of other tumour types. Clonal integration of MCV into the host genome was seen in all MCC cases and was checked by FISH in one case. A recurrent pattern of conserved viral sequences which encompassed the replication origin, the small tumour (ST), and the 5′ part of the large tumour (LT) antigen DNA sequences was observed. Both ST and LT viral sequences were found to be significantly expressed in all MCCs. Neither recurrent site of integration nor alteration of cellular genes located near the viral sequences was observed. The tight association of MCV with MCC, the clonal pattern of MCV integration, and the expression of the viral oncoproteins strongly support a causative role for MCV in the tumour process. This information will help the development of novel approaches for the assessment and therapy of MCC and biologically related tumours. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity
Authors: Yabana Takashi , Arimura Yoshiaki , Tanaka Hiroki , Goto Akira , Hosokawa Masayo , Nagaishi Kanna , Yamashita Kentaro , Yamamoto Hiroyuki , Adachi Yasushi , Sasaki Yasushi , Isobe Masaharu , Fujimiya Mineko , Imai Kohzoh , Shinomura Yasuhisa
Published: January 2009

The cellular origin, in vivo function and fate of donor bone marrow‐derived cells residing in the recipient intestinal epithelial cells, pericryptal myofibroblasts or endothelial cells remain obscure. Although ‘immunoprivileged’ mesenchymal stem cells (MSCs) are prime candidates for cell‐ and gene‐based therapy, their precise role in colitis remains largely undetermined. Using a dextran sulphate sodium (DSS) colitis with busulphan (BU)‐induced hypoplastic marrow model, we examined the therapeutic effects of MSC transplantation, focusing on the role of MSCs as both cell providers and immunomodulators. Donor‐derived MSCs were detected by eGFP immunofluorescence and fluorescence in situ hybridization for Y‐chromosome (Y‐FISH) analysis. Western blot analysis of apical‐most tight junction proteins was performed with antibodies against claudin‐2, ‐7, ‐8, ‐12, ‐13, ‐15 and ZO‐1. Cytokine and cell cycle profiles were analysed by semi‐quantitative RT‐PCR and flow cytometry. Susceptibility to DSS colitis was significantly increased by co‐existing BU‐induced bone marrow hypoplasia and this increase was significantly reduced by enhancing epithelial engraftment of MSCs, an effect depending on restoring epithelial barrier integrity rather than inhibiting host immune responses. We provide evidence that implicates MSCs in maintaining epithelial barrier function by reassembling apical‐most tight junction proteins, claudins. The therapeutic efficacy of extrinsic MSCs depends on enhancing epithelial engraftment in damaged crypts by busulphan conditioning. Such a role for the MSC‐derived intestinal cells in colitis therapy merits further examination and may offer a promising new treatment for inflammatory bowel disease (IBD). Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prenatal screening for Down syndrome: women's involvement in decision‐making and their attitudes to screening
Authors: Seror Valerie , Ville Yves
Published: January 2009

Objective

To investigate pregnant women's decisions about and attitudes towards Down syndrome screening, i.e. ultrasound at 11–14 weeks, Maternal Serum Markers (MSM) at 11–14 or 15–17 weeks and possibly invasive testing.

Method

Women having given birth to a non‐affected child were asked to fill in a self‐administered questionnaire during their stay at the maternity unit. In order to characterize women's decision‐making behaviour, a hierarchical cluster analysis was conducted and logistic regressions were performed.

Results

Four hundred women were invited to participate in the study, and 391 returned the questionnaire. Both ultrasound and biochemical screening had been proposed to 88.3% of the women. Three clusters of women who were offered ultrasound and MSM were identified. Two clusters (52% and 42% of women) differed in active versus passive involvement in decision‐making. Passively involved women frequently reported unawareness of the possibility of having to make decisions about invasive testing and/or termination of pregnancy. The third cluster (6% of women) consisted of women who declined MSM. Most of the women showed a preference for first‐trimester screening, but actively involved women were willing to pay more for MSM.

Conclusion

Providing information about the sequence of decision possibly involved in screening could contribute to better informed decisions. Copyright © 2009 John Wiley & Sons, Ltd.
Early first‐trimester free β‐hCG and PAPP‐A serum distributions in monochorionic and dichorionic twins
Authors: Linskens I. H. , Spreeuwenberg M. D. , Blankenstein M. A. , van Vugt J. M. G.
Published: January 2009

Background

In the Netherlands, prenatal screening for trisomy 21 in the first trimester of pregnancy for singletons is conducted through a combined test based on maternal age, nuchal translucency measurement and maternal serum free β‐hCG and PAPP‐A. In our clinic risk calculations in twins are currently based on the NT of both fetuses instead of the combined test. In this study we looked at differences in early first‐trimester free β‐hCG and PAPP‐A between mono‐ and dichorionic twins.

Methods

A total of 202 twin pregnant women participated in the study and agreed to donate first‐trimester serum for research.

Results

The data of 200 twins with normal outcome were used for setting up reference values for free β‐hCG and PAPP‐A. Trisomy 21 was identified in the two remaining pregnancies. The overall median weight‐corrected MoM was 1.99 for free β‐hCG, and 2.14 for PAPP‐A in all twins. Monochorionic twins have a significantly lower free β‐hCG weight‐corrected MoM (1.53 vs 2.11; Mann‐Whitney U, p = 0.002) and a significantly lower PAPP‐A weight‐corrected MoM (1.59 vs 2.40; Mann‐Whitney U, p = 0.003) compared to dichorionic.

Conclusion

This study strengthened the need to make a distinction between mono‐ and dichorionic twins for the risk calculation in Down syndrome screening as biochemical markers are significantly lower in monochorionic than in dichorionic twins. Copyright © 2009 John Wiley & Sons, Ltd.
Rapid prenatal diagnosis of common chromosome aneuploidies by QF‐PCR, results of 9 years of clinical experience
Authors: Cirigliano Vincenzo , Voglino Gianfranco , Ordoñez Elena , Marongiu Antonella , Paz Cañadas M. , Ejarque Maijo , Rueda Laura , Lloveras Elisabet , Fuster Carme , Adinolfi Matteo
Published: January 2009

Background

Despite being deliberately targeted to common chromosome aneuploidies, the rapid quantitative fluorescent polymerase chain reaction (QF‐PCR) tests can detect the majority of chromosome abnormalities in prenatal diagnosis. The main advantages of this assay are low cost, speed and automation allowing large‐scale application.

Methods

We developed a QF‐PCR test that was applied on 43 000 clinical samples reporting results in 24 h. Most common indications were biochemical risk (32%) and advanced maternal age (30%). Samples were also tested by cytogenetic analysis and the results compared.

Results

Aneuploidies involving chromosomes 21, 18, 13, X and Y were detected with 100% specificity. Several cases of partial trisomies and mosaicism were also identified. Overall 95% of clinically relevant abnormalities were readily detected and termination of affected pregnancies could be performed without waiting for the cytogenetic results.

Conclusions

Our study supports the possibility of reducing the load of prenatal cytogenetic tests if the pregnancies are carefully monitored by non‐invasive screening. In case of abnormal QF‐PCR results, medical action can be taken within few hours from sampling. In cases of negative QF‐PCR results, cytogenetic analyses might only be performed for fetuses with ultrasound abnormalities. In countries where large‐scale cytogenetic tests are not available, QF‐PCR may be used as the only prenatal diagnostic procedure. Copyright © 2009 John Wiley & Sons, Ltd.
Assessing discrepant findings between QF‐PCR on uncultured prenatal samples and karyotyping on long‐term culture
Authors: Lau Elizabeth T. , Tang Linda , Wong Cherry , Yung Hang Lam , Ghosh A. , Leung W. C. , Sin W. K. , Lau T. K. , Kung Y. Y. , Tang Mary H. Y.
Published: January 2009

Objective

To assess the prevalence of discrepant results found between quantitative fluorescent polymerase chain reaction (QF‐PCR) analysis on uncultured prenatal samples and karyotyping on long‐term culture.

Method

Results of QF‐PCR from 1932 amniotic fluid (AF) and 1132 chorionic villus (CV) samples collected from September 1999 to February 2008 were analyzed. Nature of discrepancies was categorized for normal or abnormal results from uncultured and cultured samples.

Results

A total of nine (0.8%) discrepant cases were found in the CV and six (0.3%) in AF samples. Three abnormal results involving trisomy 18 or mosaic trisomy 13 showed normal karyotype with one representing complete discordance. There were three QF‐PCR reports with initial mosaic trisomy 21 and five cases involving sex chromosome aneuploidy showing complete trisomy 21 and 45,X, respectively, after long‐term culture.

Conclusions

CV (0.8%) and AF (0.3%) samples showed discrepant results after culturing and 40% of discrepancy involved the sex chromosomes. QF‐PCR on long‐term culture was concordant with karyotyping results meaning that QF‐PCR is technically sound. Discrepant PCR findings in uncultured prenatal samples likely arose from mosaicism or preferential cell culture. Limitations in abnormal QF‐PCR results may be discussed with couples before further action. Copyright © 2009 John Wiley & Sons, Ltd.
Foetal craniopharyngioma diagnosed by prenatal ultrasonography and confirmed by histopathological examination
Authors: Joó József Gábor , Rigó János , Sápi Zoltán , Timár Botond
Published: January 2009

Background

Craniopharyngioma is an intracranial tumour, which usually develops in children and young adults and rarely occurs in intrauterine life.

Methods

In foetal life, ultrasonography and later computed tomography (CT) and magnetic resonance imaging (MRI) are regarded to be the most effective tools of diagnosis.

Results

In the seven cases published earlier, tumour size was below our finding of 96 × 80 × 65 mm3. In relation to the current case report, we aimed at surveying the available information on prenatal craniopharyngioma.

Conclusion

Although the tumour is benign, the neurological and ophthalmologic complications, arising due to its expansive growth, are suggestive of a poor prognosis. Despite the high mortality and morbidity rates, neurosurgical treatment appears to be the sole option. Copyright © 2009 John Wiley & Sons, Ltd.
Characteristics of outpatient prescriptions for frail Taiwanese elders with long‐term care needs
Authors: Chan Ding‐Cheng (Derrick) , Hao Yi‐Ting , Wu Shwu‐Chong
Published: January 2009

Objective

To describe medication prescription patterns and associated factors among frail Taiwanese elders with long‐term care needs defined as having physical or cognitive functioning impairments.

Design

Longitudinal observational study from July 2001 to June 2002.

Setting

Community and Institutions.

Participants

Nationally representative samples of 11 338 elders from the ‘Assessment of National Long‐Term Care Need in Taiwan’ (ANLTCNT).

Measurments

National identification number for each subject was linked to the National Health Insurance (NHI) claims data for outpatient clinic visits, diagnoses and medication prescriptions. For point prevalence calculation, the day of maximum number of medications prescribed during the study year was used.

Results

The mean age was 78.2 ± 7.4 years old, of whom 61% were women. The mean number of chronic condition categories was 2.9 ± 1.8. On average, subjects visited 4.1 ± 2.5 different healthcare organizations, 7.7 ± 5.3 different physicians, and received 32.9 ± 26.4 outpatient cares. The mean maximum number of prescriptions of the study year was 8.6 ± 4.3; Eighty‐four per cent of our experienced polypharmacy (prescribed with ≥5 drugs) and 31% had persistent polypharmacy (polypharmacy for ≥181 days). Increased contact with healthcare professionals and greater number of chronic condition categories were associated with the development of polypharmacy and persistent polypharmacy.

Conclusion

The excessive number of medication prescriptions and high prevalence of polypharmacy among frail Taiwanese elders raised major drug‐safety concern. Multiple healthcare providers and clinic visits were strong correlates of polypharmacy. Policies should be directed to encourage the elderly to establish primary care relationships and to promote geriatric prescription principles to improve clinical managements and outcomes. Copyright © 2009 John Wiley & Sons, Ltd.
Identification of novel Stat6 regulated proteins in IL‐4‐treated mouse lymphocytes
Authors: Tuomela Soile , Rautajoki Kirsi J. , Moulder Robert , Nyman Tuula A. , Lahesmaa Riitta
Published: January 2009

Interleukin 4 (IL‐4) has an indispensable role in the differentiation of naive T helper (Th) cells toward the Th2 phenotype and induction of B cells to produce the IgE class of Igs. By regulating these two cell types, IL‐4 has a pre‐eminent role in regulation of allergic inflammation. IL‐4‐mediated regulation of T and B cell functions is largely transmitted through signal transducer and activator of transcription 6 (Stat6). In this study, we have used metabolic labeling and 2‐D electrophoresis to detect differences in the proteomes of IL‐4 stimulated spleen mononuclear cells of Stat6−/− and wild type mice and MS/MS for protein identification. With this methodology, we identified 49 unique proteins from 21 protein spots to be differentially expressed. Interestingly, in Stat6−/− CD4+ cells the expression of isoform 2 of core binding factor b (CBFb2) was enhanced. CBFb is a non‐DNA binding cofactor for the Runx family of transcription factors, which have been implicated in regulation of Th cell differentiation. We also found cellular nucleic acid protein (CNBP) to be downregulated in Stat6−/− cells. None of the proteins identified in this study have previously been reported to be regulated via Stat6. The results highlight the importance of exploiting proteomics tools to complement the studies on Stat6 target genes identified through transcriptional profiling.
Multiplex expression cloning of blood–brain barrier membrane proteins
Authors: Agarwal Nitin , Shusta Eric V.
Published: January 2009

The blood–brain barrier (BBB) is a vascular endothelial interface that separates the brain interior from the bloodstream. Membrane proteins resident at the BBB play important functional and regulatory roles. The current study describes the development and successful implementation of a multiplex expression cloning (MEC) method to allow facile identification of BBB membrane proteins. The overriding goal of the MEC approach was to mine a BBB cDNA library and selectively isolate membrane protein‐encoding cDNAs. This selection process was achieved via fluorescence‐activated cell sorting (FACS) of cDNA‐expressing mammalian host cells for those cells that were immunolabeled with a BBB membrane protein‐specific polyclonal antiserum (BMSPA). After optimization of the host cell expression system, four selection rounds allowed the isolation of a panel of 15 unique cDNAs that encoded BBB membrane proteins. The identified proteins display significant diversity in structure, function and in vivo expression levels. The MEC approach thus proved effective for conducting moderate throughput membrane proteome analyses of the BBB while limiting any biases caused by membrane protein insolubility or low in vivo expression levels that can complicate other proteomic approaches.
Alteration in the glycan pattern of pilin in a nonmotile mutant of Synechocystis sp. PCC 6803
Authors: Kim Young Hye , Kim Jin Young , Kim Se‐Young , Lee Jeong Hwa , Lee Jin Suk , Chung Young‐Ho , Yoo Jong Shin , Park Young Mok
Published: January 2009

Pilus‐mediated motility is essential for the optimization of photosynthesis and environmental adaptation in the cyanobacterium Synechocystis sp. PCC 6803 (Syn6803). To identify the genes required for pilus‐mediated motility in Syn6803, we applied a forward genetic approach using a Tn5 mutant library and reverse genetics using interposon mutagenesis. One of the identified genes, sll0899, bears sequence similarity to acyltransferases and nucleotidyltransferases [1]. The sll0899 gene product is not involved in the transcription or translation of pilA1, which encodes pilin, the major component of pili. Instead, the sll0899::Cmr mutant produced pilins with increased molecular mass, suggesting the existence of different PTMs. Using MS, we found that the wild‐type (WT) and mutant pilins were glycosylated between amino acids 67 and 75. Analyses by quantitative MS and high‐pH anion exchange chromatography (HPAEC) revealed that the glycan in WT pilin is composed of xylose and fucose, whereas an additional sugar, rhamnose, was found in the glycan of sll0899::Cmr. Our findings suggest that an alteration in the O‐linked glycan of pilin is responsible for the loss of pilus‐mediated motility in sll0899::Cmr.
Overflow of a hyper‐produced secretory protein from the Bacillus Sec pathway into the Tat pathway for protein secretion as revealed by proteogenomics
Authors: Kouwen Thijs R. H. M. , van der Ploeg René , Antelmann Haike , Hecker Michael , Homuth Georg , Mäder Ulrike , van Dijl Jan Maarten
Published: January 2009

Bacteria secrete numerous proteins into their environment for growth and survival under complex and ever‐changing conditions. The highly different characteristics of secreted proteins pose major challenges to the cellular protein export machinery and, accordingly, different pathways have evolved. While the main secretion (Sec) pathway transports proteins in an unfolded state, the twin‐arginine translocation (Tat) pathway transports folded proteins. To date, these pathways were believed to act in strictly independent ways. Here, we have employed proteogenomics to investigate the secretion mechanism of the esterase LipA of Bacillus subtilis, using a serendipitously obtained hyper‐producing strain. While LipA is secreted Sec‐dependently under standard conditions, hyper‐produced LipA is secreted predominantly Tat‐dependently via an unprecedented overflow mechanism. Two previously identified B. subtilis Tat substrates, PhoD and YwbN, require each a distinct Tat translocase for secretion. In contrast, hyper‐produced LipA is transported by both Tat translocases of B. subtilis, showing that they have distinct but overlapping specificities. The identified overflow secretion mechanism for LipA focuses interest on the possibility that secretion pathway choice can be determined by environmental and intracellular conditions. This may provide an explanation for the previous observation that many Sec‐dependently transported proteins have potential twin‐arginine signal peptides for export via the Tat pathway.
A brief self‐administered psychological intervention to improve well‐being in patients with cancer: results from a feasibility study
Authors: Ramachandra Pranathi , Booth Sara , Pieters Thirza , Vrotsou Kalliopi , Huppert Felicia A.
Published: January 2009

Background: Patients with cancer have relatively high rates of anxiety and distress, adversely affecting their well‐being and quality of life. Recent studies indicate that addressing these symptoms could result in better response to cancer treatment. Researchers have found that interventions that focus on increasing mental awareness and the frequency of positive experiences may have a greater impact on reducing psychological morbidity and increasing quality of life than interventions that target relief of psychological symptoms.

Aim: To develop and test a brief, easy to use intervention that could improve well‐being and quality of life in cancer patients.

Methods: We developed a simple well‐being intervention that made few demands on patient time and required little training resource. Participants were randomly assigned to an intervention group or a deferred entry group. Measures of anxiety, depression, well‐being and quality of life were administered at baseline and at follow‐ups.

Results: Twenty‐two women with metastatic breast cancer and 24 men with metastatic prostate cancer were recruited from oncology clinics. Thirteen women and 14 men completed the study. Both qualitative and quantitative data showed that the intervention was acceptable to users. There was statistically significant improvement in quality of life scores on WHOQOL‐BREF post‐intervention (p=0.046). Compliance with the intervention was good.

Conclusions: This brief well‐being intervention appears to be a promising technique for improving quality of life of cancer patients, without making undue demands on staff resources or patient time. If further studies confirm its effectiveness, it could prove to be a cost‐effective intervention. Copyright © 2009 John Wiley & Sons, Ltd.
Prostatic soy isoflavone concentrations exceed serum levels after dietary supplementation
Authors: Gardner Christopher D. , Oelrich Beibei , Liu Jenny P. , Feldman David , Franke Adrian A. , Brooks James D.
Published: January 2009

BACKGROUND

The effects of soy isoflavones on prostate cancer may be concentration‐dependent. The impact of soy supplementation on isoflavone concentrations in prostate tissues and serum remain unclear.

OBJECTIVE

To assess and compare concentrations of soy isoflavones in prostate tissue and serum among 19 men with prostate cancer who had elected to undergo radical prostatectomy.

METHODS

Participants were randomized to receive either daily soy supplements (82 mg/day aglycone equivalents) or placebos for 2 weeks (14 days) prior to surgery. Serum samples were obtained at the time of the surgery. Isoflavone concentrations were measured by HPLC/ESI‐MS–MS.

RESULTS

The median (25th, 75th percentile) total isoflavone concentration in the isoflavone‐supplemented group was 2.3 µmol/L (1.2, 6.9) in the prostate tissue and 0.7 µmol/L (0.2, 1.2) in the serum. Total isoflavone concentrations in this group were an average of ∼6‐fold higher in prostate tissue compared to serum; the tissue versus serum ratio was significantly lower for genistein than daidzein, 4‐fold versus 10‐fold, P = 0.003. Tissue and serum levels of isoflavones among the placebo group were negligible with a few exceptions.

CONCLUSIONS

The findings from the present study suggest that prostate tissue may have the ability to concentrate dietary soy isoflavones to potentially anti‐carcinogenic levels. Prostate 69: 719–726, 2009. © 2009 Wiley‐Liss, Inc.
British and Indian scientists in Boston considering returning to their home countries
Authors: Harvey William S.
Published: January 2009

This paper argues that despite a sizeable literature on return migration, it is still not well understood whether highly skilled migrants are remaining in their host countries or returning to their home countries. I argue that most British and Indian scientists working in the pharmaceutical and biotechnology sector around Boston are likely to remain in the US. This provides a different perspective to many recent studies which have highlighted the temporary nature of highly skilled migration. I argue that permanent types of migration need to be placed in the context of other temporary forms of migration. Similarly to microeconomic theories of migration, I argue that professional opportunities are the principal reason why highly skilled migrants would return to their home countries. However, culture and lifestyle, family considerations, and to a lesser extent governments, are also significant in shaping migration decisions. This paper shows that there are important differences in the intentions of highly skilled migrants from developed and developing countries to return to their home countries. I argue that migrants often face conflicting loyalties in different countries, and their individual social networks with actors in their host and home countries will help them make migration decisions. Copyright © 2009 John Wiley & Sons, Ltd.
Hot embossing of pyramidal micro‐structures in PMMA for cell culture
Authors: Schneider Petra , Steitz Claudia , Schäfer Karl H. , Ziegler Christiane
Published: January 2009

For the investigation of the effect of 3‐dimensional structures upon cell attachment and growth, polymeric micropyramids with dimensions comparable to the size of cells were fabricated. Moulds for the hot embossing of the polymers were manufactured in silicon by photolithography and wet chemical etching. For an accurate casting the moulds need very smooth surfaces, which were achieved by using KOH/IPA for crystallographic etching. A PTFE‐like layer was deposited by a RIE process from C4F8 plasma to form an anti‐sticking layer on the mould surfaces to result in an easy release of the embossed substrates. Preparation methods and embossing parameters were established and optimised to emboss pyramidal structures with different base lengths and distances from 1 μm to 40 μm into PMMA. The imprinted polymeric microstructures were characterised with profilometry and SEM. First cell culture experiments were performed using neuronal and epithelial cell types on the micropyramidal surfaces to investigate their influence upon the cell‐surface interactions. While both cell types attached nicely on either plane or microstructured PMMA surfaces, especially the neurite outgrowth was influenced by the pyramidal structures. The effect of the pyramidal design upon cell development might be of potential interest for the use in cell culture and tissue engineering. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Advances of amorphous wire magnetics over 27 years
Authors: Mohri Kaneo , Humphrey Floyd B. , Panina Larissa V. , Honkura Yoshinobu , Yamasaki Jiro , Uchiyama Tsuyoshi , Hirami Matsuo
Published: January 2009

An overview of advances of the amorphous wire magnetics over the past 27 years with discoveries of extremely sensitive magnetic effects such as the large Barkhausen effect, the Matteucci effect and the magnetoimpedance effect and their successive applications to security sensor tags, pen‐inputting computer tablets and electronic compasses for mobile phones in commercial productions is presented. An important new topic of biocell magnetic field sensing in vitro and human physiological magnetic field sensing in vivo using a 10 pT amorphous wire magnetoimpedance sensor is also shown that would be improved using thinner glass‐covered amorphous wires. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Excitation relaxation in copper selenide nanowires
Authors: Juška Gediminas , Jagminas Arūnas , Gulbinas Vidmantas
Published: January 2009

Ultrafast nonequilibrium charge carrier relaxation in highly ordered Cu2–x Se nanowires of 8 nm, 13 nm and 25 nm diameter was investigated by means of femtosecond pump–probe absorption spectroscopy. Transient absorption bleaching was observed in the region of the near infrared absorption band, whereas an induced absorption dominated at higher energies. The transient absorption kinetics is almost independent of the excitation and probe wavelength and shows a biexpoenetial charge carrier recombination with the excitation intensity dependent decay rates. The initial ultrafast relaxation, which gets slower at higher excitation intensities, is followed by the slower decay component emerging at high intensities. These relaxation peculiarities are discussed in terms of recombination enhancement by intragap states, and relaxation kinetics is described by a theoretical model of two concurrent relaxation channels involving deep and shallow impurity levels. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modeling spatial learning in rats based on Morris water maze experiments
Authors: Faes Christel , Aerts Marc , Geys Helena , De Schaepdrijver Luc
Published: January 2009

The Morris water maze, developed by Morris (J Neurosci Methods 1984: 11: 47–60), is a behavioral experiment designed to test the spatial memory. When repeating the experiment several times, the changes in time (latency) and distance (path) taken to reach the platform are indicators for the learning and memory abilities of the rat. In juvenile toxicity studies, it is of interest to test whether dosing juvenile rats with some compound of interest has an effect on its learning ability. The traditional analysis uses non‐parametric tests to check for a possible dose‐effect. However, due to the many tests performed, this approach lacks power. Here, an alternative method is proposed, accounting for the longitudinal design of the study, the right‐censoring of observations when animals did not find the platform and the correlation between the time and distance taken to reach the platform. Copyright © 2009 John Wiley & Sons, Ltd.
Back to basics: explaining sample size in outcome trials, are statisticians doing a thorough job?
Authors: Carroll Kevin J.
Published: January 2009

Time to event outcome trials in clinical research are typically large, expensive and high‐profile affairs. Such trials are commonplace in oncology and cardiovascular therapeutic areas but are also seen in other areas such as respiratory in indications like chronic obstructive pulmonary disease. Their progress is closely monitored and results are often eagerly awaited. Once available, the top line result is often big news, at least within the therapeutic area in which it was conducted, and the data are subsequently fully scrutinized in a series of high‐profile publications. In such circumstances, the statistician has a vital role to play in the design, conduct, analysis and reporting of the trial. In particular, in drug development it is incumbent on the statistician to ensure at the outset that the sizing of the trial is fully appreciated by their medical, and other non‐statistical, drug development team colleagues and that the risk of delivering a statistically significant but clinically unpersuasive result is minimized. The statistician also has a key role in advising the team when, early in the life of an outcomes trial, a lower than anticipated event rate appears to be emerging. This paper highlights some of the important features relating to outcome trial sample sizing and makes a number of simple recommendations aimed at ensuring a better, common understanding of the interplay between sample size and power and the final result required to provide a statistically positive and clinically persuasive outcome. Copyright © 2009 John Wiley & Sons, Ltd.
Compensation transparency and managerial opportunism: a study of supplemental retirement plans
Authors: Kalyta Paul
Published: January 2009

Existing research on managerial compensation is based primarily on optimal contracting and managerial hegemony theories. Under the optimal contracting theory, observed compensation contracts are optimally determined, aligning the interests of managers and shareholders. Under the managerial hegemony theory, observed compensation contracts deviate from the optimum because top managers with power over boards are able to influence their own pay. I argue that the impact of managerial power over boards on managerial pay, and hence the deviation of compensation contracts from the optimum, is contingent on the transparency of managerial compensation. Within this framework, I investigate the impact of supplemental executive retirement plans (SERPs)— historically the least transparent compensation component— on opportunistic decision making. An empirical analysis based on a time series sample of CEOs of S&P/TSX60 firms provides support of the compensation transparency theory. I find that SERP benefits are primarily driven by variables proxying for CEO power over the board, whereas more transparent compensation components are primarily driven by economic factors. The results also suggest that CEOs whose SERPs are contingent on firm performance appear to reduce firm R&D expenditures as they approach retirement. Both findings provide important contributions to existing research on the impact of managerial compensation on opportunistic decisions. Copyright © 2008 John Wiley & Sons, Ltd.
Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530
Authors: Green Tim P. , Fennell Mike , Whittaker Robin , Curwen Jon , Jacobs Vivien , Allen Jack , Logie Armelle , Hargreaves Judith , Hickinson D. Mark , Wilkinson Robert W. , Elvin Paul , Boyer Brigitte , Carragher Neil , Plé Patrick A. , Bermingham Alun , Holdgate Geoffrey A. , Ward Walter H.J. , Hennequin Laurent F. , Davies Barry R. , Costello Gerard F.
Published: January 2009

AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and anti‐invasive effects in vitro, and inhibited metastasis in a murine model of bladder cancer. Antiproliferative activity of AZD0530 in vitro varied between cell lines (IC50 0.2 –>10μM). AZD0530 inhibited tumor growth in 4/10 xenograft models tested and dynamically inhibited in vivo phosphorylation of Src substrates paxillin and FAK in both growth‐inhibition‐resistant and ‐sensitive xenografts. The activity of AZD0530 in NBT‐II bladder cancer cells in vitro was consistent with inhibition of cell migration and stabilization of cell–cell adhesion. These data suggest a dominant anti‐invasive pharmacology for AZD0530 that may limit tumor progression in a range of cancers. AZD0530 is currently in Phase II clinical trials.
THE ROLE OF CHOICE IN JOHN CAGE'S ‘CHEAP IMITATION’
Authors: Jensen Marc
Published: January 2009

John Cage’s stated opinion regarding the original version of Cheap
Imitation – for solo piano – was that it constituted a breach with what he
considered the proper role of the composer to be. Despite the fact that
the actual pitch content of Cheap Imitation was derived through consultations
with the I Ching, and that the rhythmic and metric structures
were appropriated from Satie, Cage reserved for himself a great deal of
composerly control dictated only by his personal taste: the particular
kind of control which, in 1970, ran counter to what he had been doing
and writing about for years. In this sense, Cheap Imitation represents a
watershed point in Cage’s career, away from the radical indeterminacy
of the 1960s and back toward more traditional ideas of notation and
composition, containing a balance between elements that are systematized,
appropriated, and randomly generated. The work as a whole
does not simply re-embrace determinate notation, though Cage’s composed
choices are strikingly reminiscent of similar processes from his
much earlier works. As William Brooks notes, ‘Cheap Imitation looks
and sounds far more like pieces from the early 1940s than like any of its
immediate predecessors.’
The last hiccup of the old demographic regime: population stagnation and decline in late seventeenth and early eighteenth-century south-east England
Authors: Dobson Mary J.
Published: January 2009

L'époque entre le milieu du dix-septième siècle et le milieu du dix-huitième siècle s'affiche comme une période de stagnation et déclin de la population. Cette étude examine la scission de la population au niveau régional, un niveau qui a peu retenu l'attention des historiens démographes. Cette analyse régionale est axée sur trois comtés du sud-est de l'Angleterre notamment Essex, Kent et Sussex. Elle démontre que de nombreux types différents de paroisse et environs sont tous plongés dans une spirale démographique descendante. Des déclins de population pour de nombreuses paroisses du sud-est de l'Angleterre vont de pair avec des hausses de mortalité. L'auteur suggère que les mouvements de population à travers la campagne, de et vers la métropole et au delà des mers ouvraient des voies pour la propagation d'éléments pathogènes, des porteurs de maladie et leurs victimes. Le changement du cycle épidémiologique sera une des influences importantes sur les tendances démographiques de l'époque.
‘The sin of Transdanubia’: the one-child system in rural Hungary
Authors: Vasary Ildiko
Published: January 2009

Depuis la fin du dix-neuvième siècle on connaissait dans certaines régions de la Hongrie rurale, parmi les petits fermiers protestants un système rigoureux de contrôle de la fécondité. Dans ce soi-disant système à enfant unique les couples cherchaient à obtenir une famille complète à un seul enfant, fût-il garçon ou fille. Une suppression de la fécondité d'une telle ampleur était onéreuse tant pour les conditions matérielles que morales. Dépourvue des ressources d'une société moderne, toute une série de moyens sociaux furent déployés en fonction de ce système. Les modèles de nuptialité, de composition du ménage, de l'autorité au sein de la famille et tous les réseaux coopératifs de la communauté furent régiés de manière concertée et effective afin de réaliser l'idéal de la famille à enfant unique et le tout fut tordu de différentes façons. Sans l'abondante littérature qui naquit autour du problème, le système de l'enfant unique n'aurait pas dépassé le stade de l'obscur phénomène local, une bizarrerie dans les annales de la démographie mais, bien au contraire, il a été epinglé et utilisé à diverses fins tant politiques que littéraires. Dès lors l'histoire du système de l'enfant unique est devenu également celle de ceux qui l'ont observé et qui l'ont décrit.
Langzyklus bei Ovulationshemmern
Authors: Kuhl Herbert , Birkhäuser Martin , Mueck Alfred , Neulen Joseph , Thaler Christian , Kiesel Ludwig , Braendle Wilhelm
Published: January 2009

Umfragen ergeben, dass die Mehrheit der Frauen eine Änderung ihres Zyklusverhaltens im Sinne von weniger Menstruationen oder eine Amenorrhoe wünschen. Dies gilt gleichermaßen für Frauen mit Spontanzyklen wie für OH-Anwenderinnen. Die Hauptgründe dafür sind weniger Menstruationsbeschwerden, bessere Hygiene, bessere Lebensqualität und weniger Blutverlust. Bei den Frauen, die regelmäßige monatliche Blutungen wünschen, steht vor allem die Ansicht im Vordergrund, dass die Unterdrückung der Menstruation etwas «Unnatürliches» sei. Es ist deshalb notwendig, die Frauen darüber zu informieren, dass die kontrazeptive Sicherheit unter dem Langzyklus-Schema noch gesteigert wird und eine Beeinträchtigung der Fertilität nicht zu erwarten ist. Der Vorteil des Langzyklus ist eine Reduktion der Zahl der Entzugsblutungen und die Vermeidung der durch das hormonfreie Intervall ausgelösten Hormonschwankungen mit ihren psychischen und somatischen Beschwerden sowie eine erhöhte kontrazeptive Sicherheit. Folgende zyklus- und menstruationsabhängige Beschwerden werden als Indikation für die Anwendung des Langzyklus genannt: Endometriose, Menorrhagien, Dysmenorrhöen, hämorrhagische Diathesen, Uterusmyome, Polyzystisches Ovarsyndrom, Estrogen-Entzugs-Migräne in der Pillenpause sowie Prämenstruelles Syndrom.
Erhöht die hormonale Kontrazeption das Tumorrisiko?
Authors: Braendle Wilhelm , Kuhl Herbert , Mueck Alfred , Birkhäuser Martin , Thaler Christian , Kiesel Ludwig , Neulen Joseph
Published: January 2009

Als nicht-kontrazeptiven Nutzen senken orale hormonale Kontazeptiva (OH) das Risiko von bestimmten benignen und malignen Tumoren. Dazu gehören benigne Brusttumoren, Uterusmyome und funktionelle Ovarialzysten. Eine Endometriose wird selbst durch OH nicht beeinflusst, doch kommt es zu einer Verminderung der Dysmenorrhoe. Bei nieder dosierten modernen OH scheint das Risiko für Leberzelladenome und -karzinome nicht erhöht zu sein. Melanome werden durch OH nicht beeinflusst. Hinsichtlich des Mammakarzinoms kann aus den derzeit bekannten Daten kein erhöhtes Risiko abgelesen werden. Auf das Endometriumkarzinom wirken OH langfristig protektiv, ebenso auf kolorektale Karzinome. Zervixkarzinome werden nicht direkt durch OH beeinflusst, jedoch wahrscheinlich durch ein unter OH anderes Sexualverhalten. Auch unter langjähriger OH-Einnahme fand sich keine erhöhte Inzidenz von Neoplasien der Vagina oder Vulva.
Hormonale Kontrazeption – Dosierung und Verabreichungsformen
Authors: Thaler Christian , Kuhl Herbert , Mueck Alfred , Birkhäuser Martin , Braendle Wilhelm , Neulen Joseph , Keller Paul J. , Kiesel Ludwig
Published: January 2009

Seitdem der Zusammenhang zwischen der Dosis des Ethinylestradiols (EE) und dem Risiko venöser thromboembolischer Erkrankungen erkannt wurde, war die Entwicklung der Ovulationshemmer (OH) durch eine kontinuierliche Reduktion der EE-Dosis geprägt. Die damit verbundene Abnahme der Ovulationshemmwirkung der Estrogenkomponente wurde durch die Einführung potenter Gestagene kompensiert, sodass die kontrazeptive Sicherheit bei geringerem Nebenwirkungsprofil erhalten blieb. Auf Akne und Seborrhö haben auch ultra-niedrig dosierte OH einen günstigen Einfluss. Die Ergebnisse zu den Wirkungen der ultra-niedrig dosierten OH auf das Skelett sind widersprüchlich. Da es zwischen Estradiol und EE fundamentale Unterschiede gibt, sinkt das thromboembolische Risiko bei parenteraler Gabe von EE nicht ab und nimmt beim kontrazeptiven Pflaster sogar zu. EE wird nicht an SHBG gebunden. Aufgrund der Ethinylgruppe wird EE relativ langsam inaktiviert, sodass auch das in gleichmäßig niedrigen Konzentrationen in die Leber gelangende EE zahlreiche estrogenabhängige hepatische Parameter signifikant verändert. Dazu zählt auch die Hämostase und es ist anzunehmen, dass entsprechende Veränderungen für das erhöhte Thromboserisiko beim kontrazeptiven Pflaster verantwortlich sind. Eine Verkürzung des hormonfreien Intervalls der Pille auf 5 oder 4 Tage führt zu einer völligen Suppression der Ovarialfunktion, einer zuverlässigen Hemmung der Ovulation und einer Verstärkung der kontrazeptiven Wirksamkeit, auch wenn die EE-Dosis auf 20 μg oder 15 μg reduziert wird.
Disaggregation of GOES land surface temperatures using surface emissivity
Authors: Inamdar Anand K. , French Andrew
Published: January 2009

Accurate temporal and spatial estimation of land surface temperatures (LST) is important for modeling the hydrological cycle at field to global scales because LSTs can improve estimates of soil moisture and evapotranspiration. Using remote sensing satellites, accurate LSTs could be routine, but unfortunately the only instruments available to provide diurnal cycle observations have coarse spatial resolution (4 km). One approach that may help overcome the spatial resolution constraint is to disaggregate geostationary LST data using visible to thermal infrared information provided by single time of day MODIS 1 km observations. These higher‐resolution observations are correlative with observations at 4‐km scales, and thus can be used to estimate 1‐km LST values throughout a day. Inamdar et al 2008, for example, showed how GOES 10 imager and MODIS data could be combined to produce accurate half‐hourly, 1‐km LST values. However, the method disaggregated coarse LST values using Normalized Difference Vegetation Index (NDVI) data and was sometimes highly inaccurate when considering heterogeneous terrain. This problem can be greatly reduced with an alternative approach, whereby MODIS land cover emissivity data sets supply the needed 1‐km information. In a study of LST estimation over the US Southwest, diurnal disaggregation models using emissivity data were significantly more accurate than a comparable NDVI‐based model. This alternative approach which directly employs 8‐day composites of MODIS 1 km emissivity is a simple and fast method.
Are the empirical relationships describing the bio‐optical properties of case 1 waters consistent and internally compatible?
Authors: Morel André
Published: January 2009

Empirical relationships have been previously established in case 1 waters, by which some inherent optical properties such as particle absorption, scattering and attenuation coefficients, or some apparent properties, such as diffuse attenuation, reflectance, and color band ratios, have been statistically related to the chlorophyll concentration [Chl]. These relationships are at the basis of most of the bio‐optical models; with their uncertainties, they describe average trends along the [Chl] range of certain optical properties, around which a natural variability occurs. Through closure exercises and inversions, it is examined whether the presently available, and independently established, empirical relationships form a set of compatible equations. This approach also allows other, less frequently measured properties to be inferred, such as the absorption by dissolved colored matter, ay, which appears to be larger than often anticipated and to behave on average as a power function of [Chl] in case 1 waters. The spectra of the single scattering albedo of particulate matter are also derived; whatever [Chl], they distinctly exhibit the imprint of the algal pigment absorption. The consistency between the present approach and the GSM inversion scheme (developed by Garver, Siegel, and Maritorena) is also verified. Globally, it is found that within their own uncertainty (resulting from measurements) and variability levels (resulting from natural causes), the main historical relationships describing the bio‐optical state of case 1 waters appear to be mutually coherent and compatible.