bluuebunny/crossref_metadata_2025 huggingface dataset:
First‐trimester use of paroxetine and congenital heart defects: A population‐based case‐control study
Authors: Bakker Marian K. , Kerstjens‐Frederikse Wilhelmina S. , Buys Charles H. C. M. , de Walle Hermien E. K. , de Jong‐van den Berg Lolkje T. W.
Published: November 2009

BACKGROUND:

There is a need for case‐control studies of the effect of paroxetine on the occurrence of specific heart defects.

METHODS:

We performed a case‐control study with data from a population‐based birth defects registry in the Netherlands. All the children born between 1997 and 2006 were selected. Cases were defined as fetuses and children with isolated heart defects, and the controls were fetuses and children with a genetic disorder with no heart defect. We excluded children for whom there was no information on maternal medication use and deceased children and fetuses who were not examined postmortem. First‐trimester exposure to paroxetine was compared between cases and controls by calculating adjusted odds ratios (AOR).

RESULTS:

We included 678 cases with isolated heart defects and 615 controls. The first trimester exposure rate was 1.5% for cases and 1.0% for controls. After excluding mothers who used paroxetine outside the first trimester, or who had used another SSRI, we found no significantly increased risk for heart defects overall (10 exposed cases; AOR, 1.5; 95% confidence interval [CI], 0.5–4.0), but we did find a significantly increased risk for atrium septum defects (three exposed cases; AOR, 5.7; 95% CI, 1.4–23.7).

CONCLUSIONS:

Our results suggest that the use of paroxetine in early pregnancy is associated with an increased risk of atrium septum defects. The results stress the importance of studying possible teratogenic effects of a drug, preferably in regard to well‐specified malformations. Birth Defects Research (Part A) 2010. © 2009 Wiley‐Liss, Inc.
Synthesis and Crystallochromy of 1,4,7,10‐Tetraalkyltetracenes: Tuning of Solid‐State Optical Properties of Tetracenes by Alkyl Side‐Chain Length
Authors: Kitamura Chitoshi , Abe Yasushi , Ohara Takuya , Yoneda Akio , Kawase Takeshi , Kobayashi Takashi , Naito Hiroyoshi , Komatsu Toshiki
Published: November 2009

We synthesized a series of 1,4,7,10‐tetraalkyltetracenes using a new 2,6‐naphthodiyne precursor and 2,5‐dialkylfurans as starting materials (alkyl=methyl to hexyl). Surprisingly, the solid‐state color of the tetracenes ranges through yellow, orange, and red. Both yellow and red solids are obtained for the butyl derivative. Optical properties in solution show no marked differences; however, those in the solid state show characteristics that vary with alkyl side‐chain length: methyl, propyl, and pentyl derivatives are orange; ethyl and butyl derivatives are yellow; and another butyl and hexyl derivative are red. X‐ray analyses reveal that the molecular structures are planar, semi‐chair, or chair forms; the chair form takes a herringbone‐like arrangement and the other forms take slipped parallel arrangements. The mechanism of crystallochromy is discussed in terms of molecular structure, crystal packing, and calculations that take account of exciton coupling.
Supramolecular Chirality in Solvent‐Promoted Aggregation of Amphiphilic Porphyrin Derivatives: Kinetic Studies and Comparison between Solution Behavior and Solid‐State Morphology by AFM Topography
Authors: Monti Donato , De Rossi Massimo , Sorrenti Alessandro , Laguzzi Giuseppe , Gatto Emanuela , Stefanelli Manuela , Venanzi Mariano , Luvidi Loredana , Mancini Giovanna , Paolesse Roberto
Published: November 2009

The solvent‐promoted aggregation behavior of some amphiphilic porphyrin derivatives bearing chiral functionality in the form of a charged L‐proline group has been investigated by UV/Vis, resonance light scattering, fluorescence and circular dichroism spectroscopy. The investigated macrocycles give rise to aggregates featuring supramolecular chirality with high ellipticity. Kinetic studies reveal peculiar differences in the fashion of aggregation, depending on the intimate nature of the chiral functionality, namely, cationic (nitrogen‐quaternized L‐proline, 3H2) or anionic (carboxylate residue, 6H2) group. Formation of anionic 6H2 aggregates shows a diffusion‐limited kinetic behavior. AFM topography studies show formation of tighter globular structures. On the other hand, the corresponding 3H2 aggregates are formed by a cooperative, fractal‐type decay, and appear as long‐fibrous, looser structures. In the templated aggregation of 3H2 over preformed 6H2 aggregates, AFM images show formation of globular structures with reduced sizes, as a likely consequence of shorter interchromophore distances, due to favorable Coulombic interactions. The results obtained show an interesting parallelism between the solution behavior and the solid‐state aggregate structures, corroborating the sergeant–soldier effect observed in the templated aggregation. The results presented give important insights for understanding the complex mechanisms involved in these issues, which are of key importance for the development of chiral supramolecular materials and stereoselective sensors and devices.
Silicon‐ and Tin‐Based Cuprates: Now Catalytic in Copper!
Authors: Weickgenannt Andreas , Oestreich Martin
Published: November 2009

Silicon‐ and tin‐containing molecules are versatile building blocks in organic synthesis. A stalwart method for their preparation relies on the stoichiometric use of silicon‐ and tin‐based cuprates, although a few copper(I)‐catalyzed or even copper‐free protocols have been known for decades. In this Concept, we describe our efforts towards copper(I)‐catalyzed carbonsilicon and also carbontin bond formations using soft bis(triorganosilyl) and bis(triorganostannyl) zinc reagents as powerful sources of nucleophilic silicon and tin. Conjugate addition, allylic substitution, and carboncarbon multiple bond functionalization is now catalytic in copper!
Einsatzmöglichkeiten thermophysikalischer Methoden zur Lösung biochemischer und biotechnologischer Fragestellungen
Authors: Hüttl R. , Frank DC N. , Harmel J. , Lißner DC A. , Winkelmann M.
Published: November 2009

Für thermophysikalische Methoden auf den Gebieten der Biotechnologie bzw. Mikrobiologie gibt es vielfältige Anwendungsfelder. Beispiele reichen von der kalorimetrischen Ermittlung mikrobieller Aktivität über die Aufstellung von Stoffbilanzen bis hin zu Untersuchungen zum mikrobiellen Schadstoffabbau. Die vorgestellten Ergebnisse belegen die Leistungsfähigkeit thermischer Methoden zur Echtzeitdetektion mikrobieller Prozesse. Die Kombination der Universalität der kalorimetrischen Messung mit spezifischen Erkennungseinheiten im Sensor‐Kalorimeter eröffnet weiterhin die Möglichkeit der Analyse metabolischer Veränderungen. Das große Potential der thermischen Detektion liegt damit in der Überwachung, Optimierung und Kontrolle biotechnologischer Prozessabläufe.
Disruption of the blood brain barrier by brain metastases of triple‐negative and basal‐type breast cancer but not HER2/neu‐positive breast cancer
Authors: Yonemori Kan , Tsuta Koji , Ono Makiko , Shimizu Chikako , Hirakawa Akihiro , Hasegawa Tadashi , Hatanaka Yutaka , Narita Yoshitaka , Shibui Soichiro , Fujiwara Yasuhiro
Published: November 2009

BACKGROUND:

Generally, the blood‐brain barrier (BBB) of brain metastasis was thought to be disrupted.

METHODS:

We retrospectively performed immunohistochemical staining for glucose transporter 1 (GLUT1) and breast cancer resistance protein (BCRP) to evaluate the status of the BBB in resected brain metastases. Associations between expression of GLUT1 and/or BCRP and the immunohistochemical profiles of breast cancers, such as the statuses of hormone receptors, human epidermal growth factor receptor 2 (HER2/neu), and a basal‐type marker (cytokeratin 5/6, HER1), were also analyzed.

RESULTS:

The study included 29 breast cancer patients with brain metastasis who had undergone brain tumor resections. Among the 29 patients, there was no expression of GLUT1 and BCRP in the intratumor microvessels of 9 (32%) and 11 (38%) patients, respectively. There was no expression of both GLUT1 and BCRP in 8 patients (28%). The expression of GLUT1 was significantly associated with that of BCRP (P < .001). A positive correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of HER2/neu‐positive breast cancer (P = .012), while a negative correlation was observed between the expression of GLUT1 and/or BCRP and brain metastases of triple negative or basal‐type breast cancer (P = .014 and P = .003 for triple negative and basal‐type, respectively).

CONCLUSIONS:

Brain metastases of triple negative or basal‐type breast cancers may often disrupt the BBB, whereas brain metastases of HER2/neu‐positive breast cancer tend to preserve the BBB. Cancer 2010. © 2010 American Cancer Society.
Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development
Authors: Nakamura Yukiko , Lee Suni , Haddox Candace L. , Weaver Eli J. , Lemmon Vance P.
Published: November 2009

Mutations in the human L1CAM gene cause X‐linked hydrocephalus and MASA (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking, neurite branching, signaling, and interactions with the cytoskeleton. L1cam knockout (L1KO) mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves. To explore the function of the L1CD, we made three new mice lines in which different parts of the L1CD have been altered. In all mutant lines L1 protein is expressed and transported into the axon. Interestingly, these new L1CD mutant lines display normal brain morphology. However, the expression of L1 protein in the adult is dramatically reduced in the two L1CD mutant lines that lack the ankyrin‐binding region and they show defects in motor function. Therefore, the L1CD is not responsible for the major defects observed in L1KO mice, yet it is required for continued L1 protein expression and motor function in the adult. J. Comp. Neurol. 518:1113–1132, 2010. © 2009 Wiley‐Liss, Inc.
Three subdivisions of the auditory midbrain in chicks (Gallus gallus) identified by their afferent and commissural projections
Authors: Wang Yuan , Karten Harvey J.
Published: November 2009

The auditory midbrain is a site of convergence of multiple auditory channels from the brainstem. In birds, two separate ascending channels have been identified, through which time and intensity information is sent to the nucleus mesencephalicus lateralis, pars dorsalis (MLd), the homologue of the central nucleus of the mammalian inferior colliculus. Using in vivo anterograde and retrograde tracing techniques, the current study provides two lines of anatomical evidence supporting the presence of a third ascending channel to the chick MLd. First, three non‐overlapping zones of the MLd receive inputs from three distinct cell groups in the caudodorsal brainstem. The projections from the nucleus angularis (NA) and nucleus laminaris (NL) are predominantly contralateral and may correspond to the time and intensity channels. A rostromedial portion of the MLd receives bilateral projections mainly from the regio intermedius, an interposed region of cells lying at a caudal level between the NL and NA, as well as scattered neurons embedded in the 8th nerve tract, and probably a very ventral region of the NA. Second, the bilateral zones of the MLd on two sides of the brain are reciprocally connected and do not interact with other zones of the MLd via commissural connections. In contrast, the NL‐recipient zone projects contralaterally upon the NA‐recipient zone. The structural separation of the third pathway from the NA and NL projections suggests a third information‐processing channel, in parallel with the time and intensity channels. Neurons in the third channel appear to process very low frequency information including infrasound, probably utilizing different mechanisms than that underlying higher frequency processing. J. Comp. Neurol. 518:1199–1219, 2010. © 2009 Wiley‐Liss, Inc.
Morphology of dopaminergic amacrine cells in the mouse retina: Independence from homotypic interactions
Authors: Keeley Patrick W. , Reese Benjamin E.
Published: November 2009

To determine the role of homotypic interactions between neighboring dopaminergic amacrine (DA) cells upon dendritic morphogenesis, the morphology of single cells was examined relative to the positioning of all neighboring homotypic cells. For each labeled cell, the dendritic field was reconstructed, its Voronoi domain was calculated, and the two were related. The dendritic fields of DA cells were observed to be large, sparse, and highly irregular. Dendrites readily overlapped those of neighboring cells, showing no evidence for dendritic tiling or inter‐digitation consistent with homotypic repulsion or avoidance. Furthermore, a direct comparison of dendritic field area with the Voronoi domain area of the same cell showed no evidence for dendritic growth being constrained or biased by the local distribution of homotypic neighbors in wild‐type retinas. A comparison of the processes of adjacent filled cells confirmed their immediate proximity to one another within the inner plexiform layer, indicating that they do not engage in mutual avoidance by coursing at different depths. Together, these results suggest that the morphogenesis of DA cells is independent of homotypic interactions. However, in the absence of the pro‐apoptotic Bax gene, which yields a fourfold increase in DA cell number, a small but significant reduction in dendritic field size was obtained, although not so great as would be predicted by the increase in density. The present results are considered in light of recent studies on the role of cell adhesion molecules expressed by developing DA cells. J. Comp. Neurol. 518:1220–1231, 2010. © 2009 Wiley‐Liss, Inc.
Quantitative analysis of pre‐ and postsynaptic sex differences in the nucleus accumbens
Authors: Forlano Paul M. , Woolley Catherine S.
Published: November 2009

The nucleus accumbens (NAc) plays a central role in motivation and reward. While there is ample evidence for sex differences in addiction‐related behaviors, little is known about the neuroanatomical substrates that underlie these sexual dimorphisms. We investigated sex differences in synaptic connectivity of the NAc by evaluating pre‐ and postsynaptic measures in gonadally intact male and proestrous female rats. We used DiI labeling and confocal microscopy to measure dendritic spine density, spine head size, dendritic length, and branching of medium spiny neurons (MSNs) in the NAc, and quantitative immunofluorescence to measure glutamatergic innervation using pre‐ (vesicular glutamate transporter 1 and 2) and postsynaptic (postsynaptic density 95) markers, as well as dopaminergic innervation of the NAc. We also utilized electron microscopy to complement the above measures. Clear but subtle sex differences were identified, namely, in distal dendritic spine density and the proportion of large spines on MSNs, both of which are greater in females. Sex differences in spine density and spine head size are evident in both the core and shell subregions, but are stronger in the core. This study is the first demonstration of neuroanatomical sex differences in the NAc and provides evidence that structural differences in synaptic connectivity and glutamatergic input may contribute to behavioral sex differences in reward and addiction. J. Comp. Neurol. 518:1330–1348, 2010. © 2009 Wiley‐Liss, Inc.
From prejudice to discrimination: The legitimizing role of perceived threat in discrimination against immigrants
Authors: Pereira Cícero , Vala Jorge , Costa‐Lopes Rui
Published: November 2009

This research analyses the mediational role of threat perception in the relationship between prejudice and discrimination (opposition to immigration and opposition to naturalization of immigrants). In the first study, using representative samples in 21 European countries (N = 36 566) from European Social Survey (2002), we showed that the relationship between prejudice and opposition to immigration was more strongly mediated by realistic than by symbolic threat perceptions. In Study 2, using representative samples in two countries with different traditions of immigration (Switzerland, N = 940; Portugal, N = 1514), we showed that realistic threat more strongly mediated the relationship between prejudice and opposition to immigration, while only symbolic threat perception mediated the link between prejudice and opposition to naturalization. The theoretical implications of considering threat perceptions as factors that legitimize discrimination are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Perceived HRM practices, organizational commitment, and voluntary early retirement among late‐career managers
Authors: Herrbach Olivier , Mignonac Karim , Vandenberghe Christian , Negrini Alessia
Published: November 2009

Using a sample of 514 French late‐career managers representing a variety of occupations and organizations, we investigated the relations among perceived HRM practices, organizational commitment, and voluntary early retirement. We found that the provision of training opportunities was associated with the most favorable outcomes. It was related to higher affective and high‐sacrifice commitment, lower lack of alternatives commitment, and reduced voluntary early retirement. On the other hand, we found that flexible working conditions and the assignment of older workers to new roles (for example, mentor or coach) did not have the expected positive effects. In addition, our results highlight the importance of disentangling the components of continuance commitment, as high‐sacrifice commitment was associated with reduced likelihood of voluntary early retirement, while lack of alternatives commitment had the opposite effect. These findings suggest that voluntary early retirement should be incorporated as a major outcome in future organizational behavior research. © 2009 Wiley Periodicals, Inc.
Why some firms adopt telecommuting while others do not: A contingency perspective
Authors: Mayo Margarita , Pastor Juan‐Carlos , Gomez‐Mejia Luis , Cruz Cristina
Published: November 2009

Using a contingency perspective and data from 122 CEOs of Spanish firms, this paper examines what makes a firm likely to adopt telecommuting. We hypothesized that employer adoption of telecommuting would depend on organizational constraints (age and size of the firm), the international composition of the workforce, and the top executives' leadership style. In turn, we argue that firms adopting telecommuting would emphasize outcome‐based control systems. Our empirical evidence showed that telecommuting correlated with small organizational size, a high proportion of international employees, and variable compensation. A contingent reward leadership style at the top moderated the effects of firm age and internationalization on the adoption of telecommuting. © 2009 Wiley Periodicals, Inc.
Urbanization signature in the observed heavy rainfall climatology over India
Authors: Kishtawal C. M. , Niyogi Dev , Tewari Mukul , Pielke Roger A. , Shepherd J. Marshall
Published: November 2009

We assess the urbanization impacts on the heavy rainfall climatology during the Indian summer monsoon. While a number of studies have identified the impact of urbanization on local precipitation, a large‐scale assessment has been lacking. This relation between urbanization and Indian monsoon rainfall changes is investigated by analyzing in situ and satellite‐based precipitation and population datasets. Using a long‐term daily rainfall dataset and high‐resolution gridded analysis of human population, this study showed a significantly increasing trend in the frequency of heavy rainfall climatology over urban regions of India during the monsoon season. Urban regions experience less occurrences of light rainfall and significantly higher occurrences of intense precipitation compared to nonurban regions. Very heavy and extreme rainfall events showed increased trends over both urban and rural areas, but the trends over urban areas were larger and statistically more significant. Our analysis suggests that there is adequate statistical basis to conclude that the observed increasing trend in the frequency of heavy rainfall events over Indian monsoon region is more likely to be over regions where the pace of urbanization is faster. Moreover, rainfall measurements from satellites also indicate that urban areas are more (less) likely to experience heavier (lighter) precipitation rates compared to those in nonurban areas. While the mechanisms causing this enhancement in rainfall remain to be studied, the results provide the evidence that the increase in the heavy rainfall climatology over the Indian monsoon region is a signature of urban‐induced rainfall anomaly. Copyright © 2009 Royal Meteorological Society
Calculation of off‐resonance Raman scattering intensities with parametric models
Authors: Bougeard Daniel , Smirnov Konstantin S.
Published: November 2009

The paper reviews applications of parametric models for calculations of the Raman scattering intensity of materials with the main emphasis on the performance of the bond polarizability model. The use of the model in studies of polymers, aluminosilicates, and nanostructures is discussed and the existing sets of electro‐optical parameters as well as their transferability are analyzed. The paper highlights the interplay between the first‐principles and parametric approaches to the Raman intensity calculations and suggests further developments in this field. Copyright © 2009 John Wiley & Sons, Ltd.
Temperature‐dependent Raman scattering study of multiferroic MnWO4
Authors: Hoang Luc Huy , Hien Nguyen T. M. , Choi W. S. , Lee Y. S. , Taniguchi K. , Arima T. , Yoon S. , Chen X. B. , Yang In‐Sang
Published: November 2009

We have measured polarized Raman spectra of MnWO4 single crystals at low temperatures, and studied the temperature dependence of the various phonon modes. From our Raman studies of the MnWO4, a new transition temperature, ∼180 K, was found. We have completely assigned the symmetries of the 18 observed Raman modes of the MnWO4, as expected from a group theoretical analysis. These Raman modes have been classified into three groups according to weak, intermediate and strong temperature dependence of the modes in each group. Six internal modes have been identified by their weak temperature dependence of the Raman wavenumbers. The temperature dependence of the wavenumbers of the Bg modes in MgO bonds, modes of intermediate temperature dependence group, shows an anomalous behavior under 50 K. The phonon modes of strong temperature dependence show an anomalous change at ∼180 K in the linewidths. This is believed to be a new transition temperature which involves the changes in the inter‐WO6 octahedra structure. Copyright © 2009 John Wiley & Sons, Ltd.
Minocycline Block Copolymer Micelles and their Anti‐Inflammatory Effects on Microglia
Authors: Soliman Ghareb Mohamed , Choi Angela O. , Maysinger Dusica , Winnik Françoise M.
Published: November 2009

MH, a semisynthetic tetracycline antibiotic with promising neuroprotective properties, was encapsulated into PIC micelles of CMD‐PEG as a potential new formulation of MH for the treatment of neuroinflammatory diseases. PIC micelles were prepared by mixing solutions of a Ca2+/MH chelate and CMD‐PEG copolymer in a Tris‐HCl buffer. Light scattering and1H NMR studies confirmed that Ca2+/MH/CMD‐PEG core‐corona micelles form at charge neutrality having a hydrodynamic radius ≈100 nm and incorporating ≈ 50 wt.‐% MH. MH entrapment in the micelles core sustained its release for up to 24 h under physiological conditions. The micelles protected the drug against degradation in aqueous solutions at room temperature and at 37 °C in the presence of FBS. The micelles were stable in aqueous solution for up to one month, after freeze drying and in the presence of FBS and BSA. CMD‐PEG copolymers did not induce cytotoxicity in human hepatocytes and murine microglia (N9) in concentrations as high as 15 mg·mL−1after incubation for 24 h. MH micelles were able to reduce the inflammation in murine microglia (N9) activated by LPS. These results strongly suggest that MH PIC micelles can be useful in the treatment of neuroinflammatory disorders.

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Synthesis with Single Macromolecules: Covalent Connection between a Neutral Dendronized Polymer and Polyelectrolyte Chains as well as Graphene Edges
Authors: Barner Jörg , Al‐Hellani Rabie , Schlüter A. Dieter , Rabe Jürgen P.
Published: November 2009

Single chains of a neutral, dendronized polymer with peripheral azide groups (PG3A) are co‐deposited onto molecularly modified graphite substrates with a positively charged dendronized polymer (PG2) as well as with negatively charged plasmid dsDNA. PG3A is also prepared near graphite step‐edges. Single PG3A chains are moved with a scanning force microscope tip, into close contact with either of the two polyelectrolytes, as well as the step‐edge at predetermined positions. Treating these structures in situ with UV light leads to photochemically induced cross‐linking between the PG3A chains carrying azide groups and PG2, dsDNA, and graphite step‐edges, respectively, which is proven by mechanically challenging the “welding” points by pulling on the molecules with the SFM‐tip.

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Modeling Study on Effects of Liquid Propylene in Horizontally Stirred Gas‐Phase Reactors for Polypropylene
Authors: Kouzai Iku , Fukuda Keiji
Published: November 2009

Modeling study was carried out for JPP‐HORIZONE, which has horizontally stirred gas reactors in which the heat of polymerization is removed by vaporization of liquid propylene (LPP). The effects of LPP were estimated by the model which has a couple of continuous stirred bed reactors different in propylene form, gas of liquid, combined with a less stereospecific catalyst as a probe. LPP affects isotacticity further than catalyst efficiency in the developed model. Observed isotacticity was lower than that estimated by the model without LPP, which can be explained only by the presence of LPP.
Comparative resistance of food proteins to adult and infant in vitro digestion models
Authors: Dupont Didier , Mandalari Giuseppina , Molle Daniel , Jardin Julien , Léonil Joëlle , Faulks Richard M. , Wickham Martin S. J. , Clare Mills E. N. , Mackie Alan R.
Published: November 2009

IgE‐mediated allergy to milk and egg is widespread in industrialised countries and mainly affects infants and young children. It may be connected to an incomplete digestion of dietary proteins causing an inappropriate immune response in the gut. In order to study this, a biochemical model of infant gastroduodenal digestion has been developed, which has reduced levels of protease (eightfold for pepsin and tenfold for trypsin and chymotrypsin), phosphatidylcholine and bile salts, compared with the adult model. This model has been used to study the behaviour of three characterised food‐relevant proteins (bovine β‐lactoglobulin (β‐Lg), β‐casein (β‐CN) and hen's egg ovalbumin), all of which are relevant cows' milk and hens' egg allergens. Digestion products were characterised using electrophoresis, immunochemical techniques and MS. These showed that ovalbumin and β‐CN were digested more slowly using the infant model compared with the adult conditions. Resistant fragments of β‐CN were found in the infant model, which correspond to previously identified IgE epitopes. Surprisingly, β‐Lg was more extensively degraded in the infant model compared with the adult one. This difference was attributed to the tenfold reduction in phosphatidylcholine concentration in the infant model limiting the protective effect of this phospholipid on β‐Lg digestion.
The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade
Authors: Weigelt Britta , Baehner Frederick L , Reis‐Filho Jorge S
Published: November 2009

In the last decade, the development of microarrays and the ability to perform massively parallel gene expression analysis of human tumours were received with great excitement by the scientific community. The promise of microarrays was of apocalyptic dimensions, with some experts envisaging that it would be a matter of a few years for this technology to replace traditional clinicopathological markers in clinical practice and treatment decision‐making. The replacement of histopathology by high‐tech and more objective approaches to cancer diagnosis, prognostication and prediction was, at that time, a foregone conclusion. Ten years after the initial publications of translational research studies using microarrays, one cannot deny that this technology has changed the way breast cancer is perceived. It has brought the concept of breast cancer heterogeneity to the forefront of cancer research, and the fact that distinct subtypes of breast cancer are completely different diseases that affect the same anatomical site. Furthermore, it has led to the development of prognostic and predictive ‘gene signatures’, which are yet to be fully incorporated into clinical practice. Importantly, though, the prognostic and predictive power of microarrays has been shown to be complementary to, rather than a replacement for, traditional clinicopathological parameters. Here we endeavour to provide a fair and balanced assessment of what microarray‐based gene expression analysis has taught us in the last decade and its contribution to breast cancer classification, prognostication and prediction. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
CBT for violent men with antisocial personality disorder. Reflections on the experience of carrying out therapy in MASCOT, a pilot randomized controlled trial
Authors: Davidson Kate , Halford Judith , Kirkwood Lindsay , Newton‐Howes Giles , Sharp Melanie , Tata Philip
Published: November 2009

Cognitive therapy for personality disorders (CBTpd) has been developed and assessed in borderline and antisocial personality disorders (ASPD) using a variety of research methodologies from single cases to randomized controlled trials. An exploratory randomized controlled trial of CBTpd compared with the usual treatment for men with ASPD in the community allowed insights into how to carry out therapy with this group of patients who are traditionally thought of as being difficult to manage. CBTpd for ASPD is time‐limited, is problem‐focused and aims to develop new ways of thinking and behaving that would reduce anger and acts of violence and improve interpersonal relationships. Men with ASPD often held beliefs that could interfere with the development of a therapeutic relationship. The beliefs were hypothesized to have arisen from experiences of being humiliated in childhood and adolescence as well as having experienced neglect and abuse. Equally, therapists needed to be aware that in developing a compassionate formulation of the patient's problems, they should not minimize the potential for violence. Supervision of both process and content had a greater importance than in other CBT models, and supervision required recordings of clinical sessions to enable this to happen. Copyright © 2009 John Wiley & Sons, Ltd.
Experimental Study of a Compact Nanosecond Plasma Gun
Authors: Robert Eric , Barbosa Emerson , Dozias Sébastien , Vandamme Marc , Cachoncinlle Christophe , Viladrosa Raymond , Pouvesle Jean Michel
Published: November 2009

The paper presents a new discharge plasma setup, called plasma gun, allowing the generation of nanosecond duration plasma bullets from a pulsed dielectric barrier discharge reactor. These bullets propagate at very high velocity, up to 5 × 108 cm · s−1, in flexible dielectric capillaries flushed with neon or helium flow rates as low as 100 mL · min−1, over distances of a few tens of centimetres, before inducing plasma plume formation in ambient air. Time resolved nanosecond ICCD imaging show evidence for the channelled structure of the bullets which propagate along the inner surface of the dielectric guide. A few centimetres from the DBD reactor where they are generated, the plasma bullets expand with no connection to the high voltage power source. Non‐thermal air plasma plume production is described by spectroscopic measurements. The plasma gun is likely to be developed for remote high voltage fast commutation or in plasma medicine applications or for the decontamination of small diameter catheters.

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Sequence periodicity and secondary structure propensity in model proteins
Authors: Bellesia Giovanni , Jewett Andrew Iain , Shea Joan‐Emma
Published: November 2009

We explore the question of whether local effects (originating from the amino acids intrinsic secondary structure propensities) or nonlocal effects (reflecting the sequence of amino acids as a whole) play a larger role in determining the fold of globular proteins. Earlier circular dichroism studies have shown that the pattern of polar, non polar amino acids (nonlocal effect) dominates over the amino acid intrinsic propensity (local effect) in determining the secondary structure of oligomeric peptides. In this article, we present a coarse grained computational model that allows us to quantitatively estimate the role of local and nonlocal factors in determining both the secondary and tertiary structure of small, globular proteins. The amino acid intrinsic secondary structure propensity is modeled by a dihedral potential term. This dihedral potential is parametrized to match with experimental measurements of secondary structure propensity. Similarly, the magnitude of the attraction between hydrophobic residues is parametrized to match the experimental transfer free energies of hydrophobic amino acids. Under these parametrization conditions, we systematically explore the degree of frustration a given polar, non polar pattern can tolerate when the secondary structure intrinsic propensities are in opposition to it. When the parameters are in the biophysically relevant range, we observe that the fold of small, globular proteins is determined by the pattern of polar, non polar amino acids regardless of their instrinsic secondary structure propensities. Our simulations shed new light on previous observations that tertiary interactions are more influential in determining protein structure than secondary structure propensity. The fact that this can be inferred using a simple polymer model that lacks most of the biochemical details points to the fundamental importance of binary patterning in governing folding.
Solution structures and backbone dynamics of the ribosomal protein S6 and its permutant P54‐55
Authors: Öhman Anders , Öman Tommy , Oliveberg Mikael
Published: November 2009

The ribosomal protein S6 from Thermus thermophilus has served as a model system for the study of protein folding, especially for understanding the effects of circular permutations of secondary structure elements. This study presents the structure of a permutant protein, the 96‐residue P54‐55, and the structure of its 101‐residue parent protein S6wt in solution. The data also characterizes the effects of circular permutation on the backbone dynamics of S6. Consistent with crystallographic data on S6wt, the overall solution structures of both P54‐55 and S6wt show a β‐sheet of four antiparallel β‐strands with two α‐helices packed on one side of the sheet. In clear contrast to the crystal data, however, the solution structure of S6wt reveals a disordered loop in the region between β‐strands 2 and 3 (Leu43‐Phe60) instead of a well‐ordered stretch and associated hydrophobic mini‐core observed in the crystal structure. Moreover, the data for P54‐55 show that the joined wild‐type N‐ and C‐terminals form a dynamically robust stretch with a hairpin structure that complies with the in silico design. Taken together, the results explain why the loop region of the S6wt structure is relatively insensitive to mutational perturbations, and why P54‐55 is more stable than S6wt: the permutant incision at Lys54‐Asp55 is energetically neutral by being located in an already disordered loop whereas the new hairpin between the wild‐type N‐ and C‐termini is stabilizing.
Robust flow control in data‐communication networks with multiple time‐delays
Authors: Ünal Hakkı Ulaş , Ataşlar‐Ayyıldız Banu , İftar Altuğ , Özbay Hitay
Published: November 2009

Robust controller design for a flow control problem where uncertain multiple time‐varying time‐delays exist is considered. Although primarily data‐communication networks are considered, the presented approach can also be applied to other flow control problems and can even be extended to other control problems where uncertain multiple time‐varying time‐delays exist. Besides robustness, tracking and fairness requirements are also considered. To solve this problem, an ℋ︁∞optimization problem is set up and solved. Unlike previous approaches, where only a suboptimal solution could be found, the present approach allows to design an optimal controller. Simulation studies are carried out in order to illustrate the time‐domain performance of the designed controllers. The obtained results are also compared to the results of a suboptimal controller obtained by an earlier approach. Copyright © 2009 John Wiley & Sons, Ltd.
Viability for codifying and documenting architectural design decisions with tool support
Authors: Capilla Rafael , Dueñas Juan C. , Nava Francisco
Published: November 2009

Current software architecture practices have been focused on modeling and documenting the architecture of a software system by means of several architectural views. In practice, the standard architecture documentation lacks explicit description of the decisions made and their underlying rationale, which often leads to knowledge loss. This fact strongly affects the maintenance activities as we need to spend additional effort to replay the decisions made as well as to understand the changes performed in the design. Hence, codifying this architectural knowledge is a challenging task that requires adequate tool support. In this research, we test the capabilities of Architecture Design Decision Support System (ADDSS), a web‐based tool for supporting the creation, maintenance, use, and documentation of architectural design decisions (ADD) with their architectures. We used ADDSS to codify architectural knowledge and to maintain those trace links between the design decisions and other software artefacts that would help in the maintenance operations. We illustrate the usage of the tool through four different experiences and discuss the potential benefits of using this architectural knowledge and its impact on the maintenance and evolution activities. Copyright © 2009 John Wiley & Sons, Ltd.
Risk management of nanomaterials
Authors: Gwinn Maureen R. , Tran Lang
Published: November 2009

Nanotechnology has become the focus of a large amount of scientific, political, and financial interest. Limited information on the exposure to nanomaterials is available, with only a few occupational exposure studies having been performed. While laboratory animal studies on the biological effects of some nanomaterials have been published, no epidemiological studies have been reported to date. This lack of data on exposure and human health effects hinders risk assessment of these materials. As the use of nanomaterials increases rapidly, it is of vital importance that the risk assessment community understands the complexities of the issues surrounding the manufacture, use and disposal of nanomaterials, the potential of environmental and occupational exposure to human populations, as well as adverse health outcomes. For this to happen, it is in many ways necessary for the scientific community to also understand what questions risk assessors need to ask, and what research will best answer them. Risk management of nanomaterials requires more information as to the human and ecological effects of exposure to various nanomaterials. At this time, there are no specific regulations for nanomaterials, but a few efforts to include nanomaterials under existing environmental regulations have begun. The purpose of this article is to describe the potential regulations for nanomaterials, and the current issues related to the risk assessment of nanomaterials. WIREs Nanomed Nanobiotechnol 2010 2 130–137

This article is categorized under:

Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Species assortment or habitat filtering: a case study of spider communities on lake islands
Authors: Ulrich Werner , Hajdamowicz Izabela , Zalewski Marcin , Stańska Marzena , Ciurzycki Wojciech , Tykarski Piotr
Published: November 2009

Competition theory predicts that species of similar ecological niches are less likely to coexist than species with different niches, a process called species assortment. In contrast, the concept of habitat filtering implies that species with similar ecological requirements should co‐occur more often than expected by chance. Here we use environmental and ecological data to assess patterns of co‐occurrence of regional communities of spiders distributed across two assemblies of lake islands in northern Poland. We found aggregated and random co‐occurrences of species of the same genus and a significant tendency of species segregation across genera. We also found that species of the same genus react similarly to important environmental variables. A comparison of ecological traits of species of the local communities with those expected from a random sample from the regional Polish species pool corroborated partly the habitat filtering hypothesis. On the other hand, we did not find evidence for species assortment. Our results also imply that at least some observed species co‐occurrences result from niche differentiation.
Diversity and similarity in the tRNA world: Overall view and case study on malaria‐related tRNAs
Authors: Pütz Joern , Giegé Richard , Florentz Catherine
Published: November 2009

Transfer RNAs (tRNAs) are ancient macromolecules that have evolved under various environmental pressures as adaptors in translation in all forms of life but also towards alternative structures and functions. The present knowledge on both “canonical” and “deviating” signature motifs retrieved from vertical and horizontal sequence comparisons is briefly reviewed. Novel characteristics, proper to tRNAs from a given translation system, are revealed by a case study on the nuclear and organellar tRNA sets from malaria‐related organisms. Unprecedented distinctive features for Plasmodium falciparum apicoplastic tRNAs appear, which provide novel routes to be explored towards anti‐malarial drugs. The ongoing high‐throughput sequencing programs are expected to allow for further horizontal comparisons and to reveal other signatures of either full or restricted sets of tRNAs.
Deciphering synonymous codons in the three domains of life: Co‐evolution with specific tRNA modification enzymes
Authors: Grosjean Henri , de Crécy-Lagard Valérie , Marck Christian
Published: November 2009

The strategies organisms use to decode synonymous codons in cytosolic protein synthesis are not uniform. The complete isoacceptor tRNA repertoire and the type of modified nucleoside found at the wobble position 34 of their anticodons were analyzed in all kingdoms of life. This led to the identification of four main decoding strategies that are diversely used in Bacteria, Archaea and Eukarya. Many of the modern tRNA modification enzymes acting at position 34 of tRNAs are present only in specific domains and obviously have arisen late during evolution. In an evolutionary fine‐tuning process, these enzymes must have played an essential role in the progressive introduction of new amino acids, and in the refinement and standardization of the canonical nuclear genetic code observed in all extant organisms (functional convergent evolutionary hypothesis).
New specific molecular targets for radio‐chemotherapy of rectal cancer
Authors: Snipstad Kristin , Fenton Christopher G. , Kjæve Jørn , Cui Guanglin , Anderssen Endre , Paulssen Ruth H.
Published: November 2009

Patients with locally advanced rectal cancer often receive preoperative radio‐chemotherapy (RCT). The mechanisms of tumour response to radiotherapy are not understood. The aim of this study was to identify the effects of RCT on gene expression in rectal tumour and normal rectal tissue. For that purpose tissue samples from 21 patients with resectable adenocarcinomas were collected for use in whole genome‐microarray based gene expression analysis. A factorial experimental design allowed us to determine the effect of RCT on tumour tissue alone by removing the effect of radiation on normal tissue. This resulted in 1327 differentially expressed genes in tumour tissue with p<0.05. In addition to known markers for radio‐chemotherapy, a Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in gene sets associated with cell adhesion and leukocyte transendothelial migration. The profound change of cell adhesion molecule expression in rectal tumour tissue could either increase the risk of metastasis, or decrease the tumour's invasive potential.
Holocene climate changes in the mid-high-latitude-monsoon margin reflected by the pollen record from Hulun Lake, northeastern Inner Mongolia
Authors: Wen Ruilin , Xiao Jule , Chang Zhigang , Zhai Dayou , Xu Qinghai , Li Yuecong , Itoh Shigeru , Lomtatidze Zaur
Published: November 2009

Pollen-assemblage data from a sediment core from Hulun Lake in northeastern Inner Mongolia describe the changes in the vegetation and climate of the East Asian monsoon margin during the Holocene. Dry steppe dominated the lake basin from ca. 11,000 to 8000 cal yr BP, suggesting a warm and dry climate. Grasses and birch forests expanded 8000 to 6400 cal yr BP, implying a remarkable increase in the monsoon precipitation. From 6400 to 4400 cal yr BP, the climate became cooler and drier. Chenopodiaceae dominated the interval from 4400 to 3350 cal yr BP, marking extremely dry condition.Artemisiarecovered 3350-2050 cal yr BP, denoting an amelioration of climatic conditions. Both temperature and precipitation decreased 2050 to 1000 cal yr BP as indicated by decreasedArtemisiaand the development of pine forests. During the last 1000 yr, human activities might have had a significant influence on the environment of the lake region. We suggest that the East Asian summer monsoon did not become intensified until 8000 cal yr BP due to the existence of remnant ice sheets in the Northern Hemisphere. Changes in the monsoon precipitation on millennial to centennial scales would be related to ocean-atmosphere interactions in the tropical Pacific.
Radial index and Poincaré–Hopf index of 1-forms on semi-analytic sets
Authors: DUTERTRE NICOLAS
Published: November 2009

The radial index of a 1-form on a singular set is a generalization of the classical Poincaré–Hopf index. We consider different classes of closed singular semi-analytic sets innthat contain 0 in their singular locus and we relate the radial index of a 1-form at 0 on these sets to Poincaré–Hopf indices at 0 of vector fields defined onn.
Normalisation du Mini-Mental State Examination (MMSE) chez les Québécois francophones âgés de 65 ans et plus et résidant dans la communauté
Authors: Hudon Carol , Potvin Olivier , Turcotte Marie-Christine , D’Anjou Catherine , Dubé Micheline , Préville Michel , Brassard Joëlle
Published: November 2009

This study was aimed at providing normative data for the Mini-Mental State Examination (MMSE). The norms were built from a sample (n = 2409) of community-dwelling French speaking residents from Québec aged 65 and older. The analyses indicated that socio-demographic variables such as education level, age, and gender of individuals influenced significantly the scores of older adults on the MMSE. More precisely, MMSE scores increased with education level and decreased with age. Moreover, women had significantly higher scores than men. On this basis, distinct tables of normative data were produced for women and men. In each table, the MMSE scores corresponding to percentiles 5, 10, 15 and 50 were identified according to four age categories and three education levels. Overall, the use of the present normative data by clinicians will improve their accuracy in detecting cognitive impairment in older adults from Québec.