bluuebunny/crossref_metadata_2025 huggingface dataset:
Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model
Authors: Bazzoli Caroline , Retout Sylvie , Mentré France
Published: March 2009

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.
Sonographic prediction of macrosomia cannot be improved by combination with pregnancy‐specific characteristics
Authors: Balsyte D. , Schäffer L. , Burkhardt T. , Wisser J. , Kurmanavicius J.
Published: March 2009

Objective

To evaluate the predictive value of a combination of sonographic, clinical and demographic data for detecting fetal macrosomia compared to ultrasound fetal weight estimation alone.

Methods

Retrospective cohort data were obtained from 1062 pregnancies in an unselected population. Estimated fetal sonographic weight was obtained within the last week prior to delivery. Two different combination models—published by Mazouni et al. and Nahum and Stanislaw—were employed to predict the presence of macrosomia at birth in these infants. Receiver–operating characteristics (ROC) curves were generated to compare the prediction of macrosomia when using different observation methods and sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy were calculated.

Results

Macrosomia (birth weight ≥ 4000 g) was present in 135/1062 (12.7%) newborns. ROC curve analysis revealed the prediction of macrosomia using ultrasound alone to be significantly superior to the combined method of Mazouni et al. (area under the curve (AUC) 0.922, 95% CI 0.902–0.943 vs. 0.747, 95% CI 0.700–0.794, respectively; P < 0.0005), whereas the performance of the Nahum and Stanislaw equation was similar but not superior to ultrasound alone (AUC 0.895, 95% CI 0.839–0.950 vs. 0.912, 95% CI 0.867–0.958, respectively; P > 0.05). The accuracy of macrosomia prediction was similar for ultrasound alone and the Nahum and Stanislaw equation (∼90%), whereas the nomogram of Mazouni et al. reached only 51.7% accuracy (using a probability cut‐off level of 50%). The NPV was found to be over 90% for all methods.

Conclusions

Combination of sonographic estimates with clinical and demographic variables does not improve the prediction of macrosomia at delivery in comparison with a routine ultrasound scan within a week before delivery, at least in unselected populations. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Microemulsion Formation and Detergency with Oily Soil: V. Effects of Water Hardness and Builder
Authors: Tanthakit Parichat , Nakrachata‐Amorn Ampika , Scamehorn John F. , Sabatini David A. , Tongcumpou Chantra , Chavadej Sumaeth
Published: March 2009

In this study, the impact of water hardness and builder on the phase diagrams of motor oil microemulsions and the detergency of oil removal from a polyester/cotton blend was investigated. Water hardness and builder were found to have insignificant effects on the microemulsion phase diagram with motor oil. A mixed surfactant system of two parts C14–15(PO)3SO4Na, and 98 parts C12–14H25–29O(EO)5H of the total actives at 4% salinity was used to study the effect of water hardness and builders sodium tripolyphosphate (STPP) or ethylenediaminetetraacetic acid (EDTA) on detergency at 30 °C at a total active concentration of 0.3%. This formulation is in the Winsor Type III microemulsion regime. The microemulsion‐based formulation resulted in better detergency than a leading commercial liquid laundry detergent at all concentrations up to 0.5% actives. The microemulsion‐based formulation showed a plateau in detergency at >80% oil removal above 0.1% actives. The total oil removal decreased with increasing water hardness while the interfacial tension increased. When hard water was used in laundering, the total oil removal improved with increasing concentrations of STPP or EDTA up to stoichiometric levels, with STPP being slightly more effective than EDTA on a molar basis. Even high builder concentration could not improve hard water detergency to that of soft water. A significant fraction of oil removal occurred in the rinse steps vs. the wash step. Increasing water hardness reduced this fractional oil removal in the rinse steps, but it was still over half of total oil removal at 1,000 ppm water hardness.
The plasmid encoding HSP47 enhances collagen expression and promotes skin wound healing in an alloxan‐induced diabetic model
Authors: Wang Zuolin , Li Lin
Published: March 2009

The objective of this work was initially to investigate the effects on skin wound healing process by local injection of HSP47 recombinant plasmid in an alloxan‐induced diabetic rat model and assess the possibility and utility of gene therapy based on HSP47 plasmid to improve the diabetic skin wound healing. Rats were injected intraperitoneally with alloxan (120 mg/kg) to induce diabetes. The fragment containing the rat 47 kDa heat shock protein (HSP47) gene lacking its own promoter was cloned into plasmids containing a promoter and green fluorescent protein (GFP). The resulting gene constructs were first tested in vitro using 3T3 fibroblast cell line and subsequently in vivo after inducing wounds with alloxan in diabetic rats. Immunohistochemistry, quantitative fluorescent RT‐PCR, and Western blotting 3–5 days after plasmid injection were performed to measure the expression changes of HSP47 and collagen I. The results demonstrate an increase of HSP47 levels in vitro in 3T3 fibroblast cells and in vivo in diabetic rat after treatment with plasmids expressing HSP47. The level of collagen I around the wound during the repair process was higher in the treated group than that in the control group, indicating that the constructs may have use in human gene therapy in cases of impaired skin wound healing in diabetes.
Guidelines on the management of fibromyalgia syndrome – A systematic review
Authors: Häuser Winfried , Thieme Kati , Turk Dennis C.
Published: March 2009

We compared the methodology and the recommendations of evidence‐based guidelines for the management of fibromyalgia syndrome (FMS) to give an orientation within the continuously growing number of reviews on the therapy of FMS. Systematic searches up to April 2008 of the US‐American National Guideline Clearing House, the Scottish Intercollegiate Guidelines Network, the Association of the Scientific Medical Societies in Germany (AWMF) and Medline were conducted. Three evidence‐based guidelines for the management of FMS published by professional organizations were identified: The American Pain Society (APS) (2005), the European League Against Rheumatism (EULAR) (2007), and the AWMF (2008). The steering committees and panels of APS and AWMF were comprised of multiple disciplines engaged in the management of FMS and included patients, whereas the task force of EULAR only consisted of physicians, predominantly rheumatologists. APS and AWMF ascribed the highest level of evidence to systematic reviews and meta‐analyses, whereas EULAR credited the highest level of evidence to randomised controlled studies. Both APS and AWMF assigned the highest level of recommendation to aerobic exercise, cognitive‐behavioral therapy, amitriptyline, and multicomponent treatment. In contrast, EULAR assigned the highest level of recommendation to a set of to pharmacological treatment. Although there was some consistency in the recommendations regarding pharmacological treatments among the three guidelines, the APS and AWMF guidelines assigned higher ratings to CBT and multicomponent treatments. The inconsistencies across guidelines are likely attributable to the criteria used for study inclusion, weighting systems, and composition of the panels.
Populism and euroscepticism: Towards uncivil society?
Authors: Ruzza Carlo
Published: March 2009

This paper examines and classifies “uncivil society” in Europe, that is, a set of associational activities characterized by discursively exclusionist, undemocratic or violent features. With particular reference to organizations connected to the political right, it examines the relation between political systems and civil society, identifying the factors that have made civil society relevant for political actors and pointing to a relation of mutual dependence between the associational world and political movements and parties.

It is argued that membership in uncivil society organizations is an alternative type of political participation which articulates growing anti-political sentiments, and that the emergence of uncivil society activities is rooted in newly relevant conceptions of social and political life which are anti-modern and based on ascriptive criteria of membership. Uncivil society organizations are classified as racist, nationalist and populist, and characterized as biologically essentialist, or territorially or culturally exclusionist.
“THE MOMENT OF SOCIAL SCIENCE”: THEDECADE PHILOSOPHIQUEAND LATE EIGHTEENTH-CENTURY FRENCH THOUGHT
Authors: SONENSCHER MICHAEL
Published: March 2009

The first issue of theDécade philosophiqueappeared on 29 April 1794. In all, fifty-four volumes of the journal were published between that date and 1807, when, on Napoleon's orders, it was forced to merge with theMercure français. TheDécadewas published three times a month (taking its name from its appearance on the tenth day of each month of the French republican calendar) and the periodical soon became one of the intellectual powerhouses of the French republic after Robespierre. But quite what, in this particular setting, an intellectual powerhouse might have been is still an open question. Alongside Immanuel Kant or Jeremy Bentham, and their vast and varied intellectual legacies, the significance of the dozens of writers, including Pierre-Jean-Georges Cabanis, Pierre-Samuel Dupont de Nemours and Jean-Baptiste Say, who contributed to theDécade, is now more difficult to specify. There have, of course, been several fine studies of theDécadeand its contributors, notably by Joanna Kitchen and Marc Régaldo, and more broadly by Sergio Moravia, Martin Staum and Cheryl Welch. But it is still somewhat easier to associate the periodical with a number of keywords, such asidéologieandscience sociale, than with anything comparable to those more comprehensively articulated bodies of thought that came to be labelled “idealism” or “utilitarianism”. “Ideologism” never seems to have existed, and certainly never caught on. But this very indeterminacy may still be an advantage. It may help to open up, both historically and analytically, rather more of the intellectual space once covered by the broad range of subjects and arguments that first helped to shape—and then came to be buried by—idealism and utilitarianism.
ON TRANSCENDENTALISM: ITS HISTORY AND USES
Authors: VON FRANK ALBERT J.
Published: March 2009

If any student, graduate or advanced undergraduate, should offer to delve deeper than survey samples and seriously “take on” the Transcendentalists, he or she would be well advised to begin with the histories by Barbara Packer and Philip Gura. For that matter, these sharply differing studies will undoubtedly provoke and clarify the thinking of even the most seasoned scholars, especially if they were to read these works against each other. The more specialized though no less interesting monograph by Elisabeth Hurth, which is not offered as an introductory overview, nevertheless comprises a fully imagined history in its own right, as it places Transcendentalism in the context of crucial nineteenth-century German innovations in Protestant thought, and of the American movement's thence-derived tendency—as its critics alleged—to “atheism.” These three books, as a group, raise interesting questions about how literary history is now being written, what purposes such studies can serve, what coherence “Transcendentalism” might yet retain as a subject of useful historical inquiry, and what kind of importance the movement might have for readers today.
Unveiling the Secrets of the Galactic bulge through stellar abundances in the near-IR: a VLT/Crires project
Authors: Ryde Nils
Published: March 2009

The formation and evolution of the Milky Way bulge can be constrained by studying elemental abundances of bulge stars. Due to the large and variable visual extinction in the line-of-sight towards the bulge, an analysis in the near-IR is preferred. Here, I will present some preliminary results of an on-going project in which elemental abundances, especially those of the C, N, and O elements, of bulge stars are investigated by analysing CRIRES spectra observed with the VLT.
Clinical Utility of Waist Circumference in Predicting All‐cause Mortality in a Preventive Cardiology Clinic Population: A PreCIS Database Study
Authors: Bajaj Harpreet S. , Brennan Danielle M. , Hoogwerf Byron J. , Doshi Krupa B. , Kashyap Sangeeta R.
Published: March 2009

Although obesity is a risk factor for mortality, it is unclear whether waist circumference (WC) is a better predictor of mortality than BMI in a clinical setting of patients at high risk for coronary artery disease (CAD). Thus, we compared the association between WC and BMI with all‐cause mortality in relation to traditional CAD risk factors in a high‐risk cohort. Study population included 5,453 consecutive new patients seen between 1996 and 2005 for management of CAD risk factors in a preventive cardiology clinic. Mortality was determined from the Social Security Death Index. There were 359 deaths over a median follow‐up of 5.2 years. Mortality was greater in high (>102 cm in men and >88 cm in women) vs. normal WC in both genders (P < 0.01). The unadjusted Cox proportional hazard ratio (HR) for continuous WC (per cm) was 1.02 (P < 0.001) in both genders and remained significant after adjustment for CAD risk factors (HR = 1.01 in men, HR = 1.03 in women, both P < 0.05). BMI did not associate statistically with mortality. WC associated with diabetes mellitus (DM) and CAD prevalence (P < 0.001). BMI associated only with DM (P < 0.001) and this association disappeared when WC was added to the model. We conclude that WC is an independent predictor of all‐cause mortality in a preventive cardiology population. These data affirm the clinical importance of WC measurements for mortality, DM, and CAD risk prediction and suggest that obesity‐specific interventions targeting WC in addition to traditional risk factor management may favorably impact these outcomes.
Investigation of the Locus Near MC4R With Childhood Obesity in Americans of European and African Ancestry
Authors: Grant Struan F.A. , Bradfield Jonathan P. , Zhang Haitao , Wang Kai , Kim Cecilia E. , Annaiah Kiran , Santa Erin , Glessner Joseph T. , Thomas Kelly , Garris Maria , Frackelton Edward C. , Otieno F. George , Shaner Julie L. , Smith Ryan M. , Imielinski Marcin , Chiavacci Rosetta M. , Li Mingyao , Berkowitz Robert I. , Hakonarson Hakon
Published: March 2009

Recently a modest, but consistently, replicated association was demonstrated between obesity and the single‐nucleotide polymorphism (SNP), rs17782313, 3′ of the MC4R locus as a consequence of a meta‐analysis of genome‐wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European‐American (EA) obese children (BMI ≥95th percentile) and 3,960 EA controls (BMI <95th percentile), as well as 1,008 African‐American (AA) obese children and 2,715 AA controls. rs571312, rs10871777, and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054), and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all 30 SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3′ to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs.
High Performance Liquid Chromatography
Authors: Stuart Brian , Prichard Elizabeth
Published: March 2009

For those new to this technique, this guide provides basic tips, key skills, awareness and guidance on good practice of High Performance Liquid Chromatography (HPLC). It will help build understanding of the important issues to consider during analysis and how to develop further skills. HPLC is one of the most widely used techniques in industry to separate and analyse compounds through the mass transfer of analytes between stationary and mobile phases. This guide will prove an invaluable introduction to the technique. Starting with a look at the basic theory, the guide goes on to describe HPLC components, system parameters, suitability checks and testing. Later sections cover calibration, problem solving and data handling. High Performance Liquid Chromatography is one of the Practical Laboratory Skills Training Guides, a series that aims to make achieving best practice easy. These invaluable manuals will enable both experienced and inexperienced staff to get the essential basics of any experiment right simply by following the clear and easy to use instructions provided. The guides are written by experienced scientists and include minimal theory, plenty of practical exercises in order to assess competence, and trouble shooting information.
Nuclear translocation and signalling of L1-CAM in human carcinoma cells requires ADAM10 and presenilin/γ-secretase activity
Authors: Riedle Svenja , Kiefel Helena , Gast Daniela , Bondong Sandra , Wolterink Silke , Gutwein Paul , Altevogt Peter
Published: March 2009

L1-CAM (L1 cell-adhesion molecule), or more simply L1, plays an important role in the progression of human carcinoma. Overexpression promotes tumour-cell invasion and motility, growth in nude mice and tumour metastasis. It is feasible that L1-dependent signalling contributes to these effects. However, little is known about its mechanism in tumour cells. We reported previously that L1 is cleaved by ADAM (adisintegrin and metalloprotease) and that the cytoplasmic part is essential for L1 function. Here we analysed more closely the role of proteolytic cleavage in L1-mediated nuclear signalling. Using OVMz carcinoma cells and L1-transfected cells as a model, we found that ADAM10-mediated cleavage of L1 proceeds in lipid raft and non-raft domains. The cleavage product, L1-32, is further processed by PS (presenilin)/γ-secretase to release L1-ICD, an L1 intracellular domain of 28 kDa. Overexpression of dominant-negative PS1 or use of a specific γ-secretase inhibitor leads to an accumulation of L1-32. Fluorescence and biochemical analysis revealed a nuclear localization for L1-ICD. Moreover, inhibition of ADAM10 and/or γ-secretase blocks nuclear translocation of L1-ICD and L1-dependent gene regulation. Overexpression of recombinant L1-ICD mediates gene regulation in a similar manner to full-length L1. Our results establish for the first time that regulated proteolytic processing by ADAM10 and PS/γ-secretase is essential for the nuclear signalling of L1 in human carcinoma cell lines.
Dynamic interaction of hTRPC6 with the Orai1–STIM1 complex or hTRPC3 mediates its role in capacitative or non-capacitative Ca2+ entry pathways
Authors: Jardin Isaac , Gómez Luis J. , Salido Gines M. , Rosado Juan A.
Published: March 2009

TRPC (canonical transient receptor potential) channel subunits have been shown to assemble into homo- or hetero-meric channel complexes, including different Ca2+-handling proteins, required for the activation of CCE (capacitative Ca2+ entry) or NCCE (non-CCE) pathways. In the present study we found evidence for the dynamic interaction between endogenously expressed hTRPC6 (human TRPC6) with either both Orai1 and STIM1 (stromal interaction molecule 1) or hTRPC3 to participate in CCE or NCCE. Electrotransjection of cells with an anti-hTRPC6 antibody, directed towards the C-terminal region, reduces CCE induced by TPEN [N,N,N′,N′-tetrakis-(2-pyridylmethyl)-ethylenediamine], which reduces the intraluminal free Ca2+ concentration. Cell stimulation with thrombin or extensive Ca2+-store depletion by TG (thapsigargin)+ionomycin enhanced the interaction between hTRPC6 and the CCE proteins Orai1 and STIM1. In contrast, stimulation with the diacylglycerol analogue OAG (1-oleoyl-2-acetyl-sn-glycerol) displaces hTRPC6 from Orai1 and STIM1 and enhances the association between hTRPC6 and hTRPC3. The interaction between hTRPC6 and hTRPC3 was abolished by dimethyl-BAPTA [1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid] loading, which indicates that this phenomenon is Ca2+-dependent. These findings support the hypothesis that hTRPC6 participates both in CCE and NCCE through its interaction with the Orai1–STIM1 complex or hTRPC3 respectively.
Haemodialysis acutely reduces the plasma levels of ADMA without reversing impaired NO-dependent vasodilation
Authors: Engelberger Rolf P. , Teta Daniel , Henry Hughes , De Senarclens Olivier , Dischl Benoît , Liaudet Lucas , Burnier Michel , Waeber Bernard , Feihl François
Published: March 2009

End-stage renal disease patients have endothelial dysfunction and high plasma levels of ADMA (asymmetric ω-NG,NG-dimethylarginine), an endogenous inhibitor of NOS (NO synthase). The actual link between these abnormalities is controversial. Therefore, in the present study, we investigated whether HD (haemodialysis) has an acute impact on NO-dependent vasodilation and plasma ADMA in these patients. A total of 24 patients undergoing maintenance HD (HD group) and 24 age- and gender-matched healthy controls (Control group) were enrolled. The increase in forearm SkBF (skin blood flow) caused by local heating to 41 °C (SkBF41), known to depend on endothelial NO production, was determined with laser Doppler imaging. SkBF41 was expressed as a percentage of the vasodilatory reserve obtained from the maximal SkBF induced by local heating to 43 °C (independent of NO). In HD patients, SkBF41 was assessed on two successive HD sessions, once immediately before and once immediately after HD. Plasma ADMA was assayed simultaneously with MS/MS (tandem MS). In the Control group, SkBF41 was determined twice, on two different days, and plasma ADMA was assayed once. In HD patients, SkBF41 was identical before (82.2±13.1%) and after (82.7±12.4%) HD, but was lower than in controls (day 1, 89.6±6.1; day 2, 89.2±6.9%; P<0.01 compared with the HD group). In contrast, plasma ADMA was higher before (0.98±0.17 μmol/l) than after (0.58±0.10 μmol/l; P<0.01) HD. ADMA levels after HD did not differ from those obtained in controls (0.56±0.11 μmol/l). These findings show that HD patients have impaired NO-dependent vasodilation in forearm skin, an abnormality not acutely reversed by HD and not explained by ADMA accumulation.
Annealing effects on optical properties of low temperature grown ZnO nanorod arrays
Authors: Yang L. L. , Zhao Q. X. , Willander M. , Yang J. H. , Ivanov I.
Published: March 2009

Vertically well-aligned ZnO nanorods on Si substrates were prepared by a two-step chemical bath deposition method. The structure and optical properties of the grown ZnO nanorods were investigated by Raman and photoluminescence spectroscopy. The results showed that after an annealing treatment at around 500 °C in air atmosphere, the crystal structure and optical properties became much better due to the decrease in surface defects. The resonant Raman measurements excited by 351.1 nm not only revealed that the surface defects play a significant role in the as-grown sample, which was supported by low temperature time-resolved photoluminescence measurements, but also suggested that the strong intensity increase in some Raman scatterings was due to both outgoing resonant Raman scattering effect and deep level defect scattering contribution for ZnO nanorods annealed from 500 to 700 °C.
Magnetic force microscopy of alternating magnetic field gradient by frequency modulation of tip oscillation
Authors: Saito H. , Ikeya H. , Egawa G. , Ishio S. , Yoshimura S.
Published: March 2009

A new magnetic force microscopy (MFM) technique for measuring alternating magnetic field (ac magnetic field) was proposed by using frequency modulation (FM) phenomenon of tip oscillation. We detected a narrowband FM phenomenon in the tip oscillation of a high-coercivity MFM tip by applying an ac magnetic field to the tip by using a metal-in-gap (MIG) type ring head. In the experiment, the MFM tip was driven at a constant frequency fc near the resonant frequency of the cantilever by a piezoelectric element, and the ac magnetic field with a frequency fm up to 10 kHz was applied to the MFM tip. Two sideband spectra with a frequency of fc±fm were observed by applying ac magnetic field. The intensity of sideband spectra increased linearly with increasing applied current value of the MIG head. It was observed that FM occurred from the analysis of frequency spectra of the MFM signals. This FM phenomenon is caused by the force applied on the cantilever by the field gradient of the head. The FM phenomenon is understood by solving the differential equation for the harmonic oscillator of which the effective spring constant is changed periodically by ac magnetic field. The FM phenomenon can be used for imaging ac magnetic fields.
Magnetic phase transitions in R5NiPb3 (R=Ce, Nd, and Gd)
Authors: Goruganti V. , Rathnayaka K. D. D. , Ross Joseph H.
Published: March 2009

We report magnetic and thermodynamic measurements for R5NiPb3 (R=Ce, Nd, Gd). Gd5NiPb3 has a transition at 68K, apparently ferrimagnetic from specific heat and magnetization measurements. For Ce5NiPb3, a phase transition is observed in heat capacity at 48 K, with the field dependence of heat capacity and magnetization also indicating ferrimagnetic behavior. Ce5NiPb3 shows metamagnetism at low temperatures, behavior rather similar to Nd5NiPb3 with its previously reported magnetic ordering below 42 K. Using nonmagnetic La5NiPb3, we isolated the magnetic heat capacity for all three materials. The results include a relatively large linear-T term in the specific heat and integrated magnetic entropies consistently smaller than expected.
Terahertz laser modulation of electron beams
Authors: Neumann J. G. , Fiorito R. B. , O’Shea P. G. , Loos H. , Sheehy B. , Shen Y. , Wu Z.
Published: March 2009

The study of modulated electron beams is important because they can be used to produce coherent radiation, but the modulations can cause unwanted instabilities in some devices. Specifically, in a free electron laser, proper prebunching at the desired emission frequency can enhance performance, while bunching resulting from instabilities and bunch compression schemes can degrade performance. In a photoinjector accelerator, tailoring the shape of the drive laser pulse could be used as a technique to either enhance or mitigate the effect of these modulations. This work explores the possibility of creating deeply modulated electron beams at the photocathode by using a modified drive laser designed to produce multiple subpicosecond pulses repeated at terahertz frequencies. Longitudinal space charge forces can strongly influence the evolution of modulations by converting density modulations to energy modulations. Experiments at the Source Development Laboratory electron accelerator at Brookhaven National Laboratory and PARMELA simulations are employed to explore the dynamics of electron beams with varying charge and with varying initial modulation. Finally, terahertz light generated by a transition radiator is used to confirm the structure of the electron beam.
Conductance modulation and spin polarization in anisotropic Rashba ring interferometers
Authors: Jalil M. B. A. , Tan S. G.
Published: March 2009

We investigate the ballistic spin and charge transport in an anisotropic Rashba ring interferometer with an asymmetry due to either (i) a variable azimuthal position (ϕc) of the collector electrode, or (ii) different Rashba constants (αRu and αRl) for the upper and lower halves of the ring. The transmitted conductance and spin polarization are calculated at the collector by considering the interference of the electron wave functions from the upper and lower halves. These show strong modulation with ϕc and αR, the latter of which can be varied with a gate voltage.
Comparison of the 3ω method and time-domain thermoreflectance for measurements of the cross-plane thermal conductivity of epitaxial semiconductors
Authors: Koh Yee Kan , Singer Suzanne L. , Kim Woochul , Zide Joshua M. O. , Lu Hong , Cahill David G. , Majumdar Arun , Gossard Arthur C.
Published: March 2009

The 3ω technique and time-domain thermoreflectance (TDTR) are two experimental methods capable of measuring the cross-plane thermal conductivity of thin films. We compare the cross-plane thermal conductivity measured by the 3ω method and TDTR on epitaxial (In0.52Al0.48)x(In0.53Ga0.47)1−xAs alloy layers with embedded ErAs nanoparticles. Thermal conductivities measured by TDTR at low modulation frequencies (∼1 MHz) are typically in good agreement with thermal conductivities measured by the 3ω method. We discuss the accuracy and limitations of both methods and provide guidelines for estimating uncertainties for each approach.
MoO
x
modified ZnGaO based transparent conducting oxides
Authors: Dutta Titas , Gupta P. , Bhosle V. , Narayan J.
Published: March 2009

We report here the growth of high work function bilayered structures of thin MoOx (2.0<x<2.75) layer (few nanometers) on Zn0.95Ga0.05O films by pulsed laser deposition (PLD) on glass and sapphire substrates for transparent electrode applications. It was found that the films were highly textured along [0001] direction. The crystalline quality of the films deposited at different substrate temperatures was investigated by x-ray diffraction, transmission electron microscopy (TEM) imaging, and selected area diffraction pattern (SAED). In the MoOx layer, molybdenum exists in Mo4+, Mo5+, and Mo6+ oxidation states, and the ratio of (Mo4++Mo5+) to Mo6+ was determined to be ∼2:1. The bilayer films showed good optical transparency (≥80%) and low resistivity of ∼10−4 Ω cm. Different transport behavior of the MoOx/ZnGa0.05O films grown at different Ts (substrate temperature) was observed in temperature-dependent resistivity measurements. The bilayer film at higher Ts showed metallic conductivity behavior down to 113 K. Moreover, a blueshift of the absorption edge in the transmission spectrum was observed with the increase in Ts, indicating an increase in the carrier concentration. It was observed that the ZnGa0.05O films with ultrathin MoOx (∼1–2 nanometers) overlayer showed a higher work function (varying from 4.7 to 5.1 eV) as compared to the single layer ZnGa0.05O film work function (∼4.4 eV). A correlation between the surface work function and MoOx layer thickness is observed. The higher work function of the MoOx overlayer is envisaged to improve the transport of the carriers across the heterojunction in a solid state device, thus resulting an increase in device efficiency.
Pore orientation and silylation effects on mesoporous silica film properties
Authors: Singh A. P. , Gandhi D. D. , Singh B. , Simonyi E. , Liniger E. G. , Nitta S. V. , Lane M. W. , Ramanath G.
Published: March 2009

Low dielectric permittivity mesoporous silica (MPS) films with high mechanical and chemical stability are attractive for electrically isolating multilevel wiring in future nanodevices. Here, we show that pore structure is a crucial determinant of chemically induced leakage currents in pristine and silylated MPS films and strongly influences film stiffness and hardness in silylated MPS films. Films with three-dimensional pore networks exhibit superior mechanical properties than films with cylindrical pores oriented exclusively parallel to the surface. The latter, however, exhibit a fourfold higher resilience to copper diffusion. These differences are attributed to the pore structure and its influence on silylation-induced bond-breaking and passivation.
Critical role of interface states for spin-dependent tunneling in half-metallic Co2MnSi-based magnetic tunnel junctions investigated by tunneling spectroscopy
Authors: Ishikawa Takayuki , Itabashi Naoki , Taira Tomoyuki , Matsuda Ken-ichi , Uemura Tetsuya , Yamamoto Masafumi
Published: March 2009

We investigated at 4.2 K the differential conductance (dI/dV) versus V characteristics of fully epitaxial Co2MnSi/MgO/Co2MnSi magnetic tunnel junctions (MTJs) featuring high tunnel magnetoresistance ratios of about 700% at 4.2 K (about 180% at room temperature). We developed a tunneling model to explain the observed tunneling spectra and showed the critical role played by interface states for minority spins existing around the Fermi level of Co2MnSi electrodes facing a MgO tunnel barrier in the spin-dependent tunneling characteristics of these MTJs with half-metallic electrodes.
Effect of channel doping concentration and thickness on device performance for In0.53Ga0.47As metal-oxide-semiconductor transistors with atomic-layer-deposited Al2O3 dielectrics
Authors: Zhao Han , Zhu Feng , Chen Yen-Ting , Yum Jung Hwan , Wang Yanzhen , Lee Jack C.
Published: March 2009

We have investigated the channel doping concentration and channel thickness dependence of device performance for In0.53Ga0.47As metal-oxide-semiconductor transistors with atomic layer deposited Al2O3 dielectrics. We found that undoped channel provides the highest drive current of 125 mA/mm for 5 μm gate length. With proper substrate doping concentration (5×1016/cm3), reasonable subthreshold swing (104 mV/decade) can be achieved for 4.7 nm equivalent oxide thickness. Thinner InGaAs channel exhibits lowest off-current density of 4.0×10−6 mA/mm.
Blue to deep UV light emission from a p-Si/AlN/Au heterostructure
Authors: Zhao J. L. , Tan S. T. , Iwan S. , Sun X. W. , Liu W. , Chua S. J.
Published: March 2009

Undoped AlN thin film has been grown on p-Si (111) by metal-organic chemical-vapor deposition. The p-Si/AlN/Au heterostructured light-emitting diode was further fabricated and investigated. The current-voltage characteristic showed a typical back-to-back diode behavior, which is responsible for the electroluminescence at both forward and reverse bias. A deep UV emission at 283 nm as well as a UV emission at 380 nm was observed from the forward biased p-Si/AlN/Au diode, while a blue emission at 490 nm was detected from the diode under reverse bias. The recombination mechanism for each emission band was discussed based on the energy band diagram.
PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool
Authors: Li Wenjing , Ferguson Brian J. , Khaled Walid T. , Tevendale Maxine , Stingl John , Poli Valeria , Rich Tina , Salomoni Paolo , Watson Christine J.
Published: March 2009

Nuclear domains of promyelocytic leukemia protein (PML) are known to act as signaling nodes in many cellular processes. Although the impact of PML expression in driving cell fate decisions for injured cells is well established, the function of PML in the context of tissue development is less well understood. Here, the in vivo role of PML in developmental processes in the murine mammary gland has been investigated. Data are presented showing that expression of PML is tightly regulated by three members of the Stat family of transcription factors that orchestrate the functional development of the mammary secretory epithelium during pregnancy. Developmental phenotypes were also discovered in the virgin and pregnant
Pml
null mouse, typified by aberrant differentiation of mammary epithelia with reduced ductal and alveolar development. PML depletion was also found to disturb the balance of two distinct luminal progenitor populations. Overall, it is shown that PML is required for cell lineage determination in bi-potent luminal progenitor cells and that the precise regulation of PML expression is required for functional differentiation of alveolar cells.
Assembly and dynamics of proteins of the longitudinal and junctional sarcoplasmic reticulum in skeletal muscle cells
Authors: Cusimano Vincenza , Pampinella Francesca , Giacomello Emiliana , Sorrentino Vincenzo
Published: March 2009

The sarcoplasmic reticulum (SR) of skeletal muscle cells is a complex network of tubules and cisternae that share a common lumen delimited by a single continuous membrane. The SR contains longitudinal and junctional domains characterized by distinctive patterns of protein localization, but how SR proteins reach and/or are retained at these sites is not known. Here, we report that the organization of longitudinal SR proteins is a slow process characterized by temporally distinct patterns of protein localization. In contrast, junctional SR proteins rapidly and synchronously assembled into clusters which, however, merged into mature triadic junctions only after completion of longitudinal SR protein organization. Fluorescence recovery after photobleaching experiments indicated that SR organization was accompanied by significant changes in the dynamic properties of longitudinal and junctional proteins. The decrease in mobility that accompanied organization of the longitudinal SR proteins ank1.5-GFP and GFP-InsP3R1 was abrogated by deletion of specific binding sites for myofibrillar or cytoskeletal proteins, respectively. Assembly of junctional SR domains was accompanied by a strong decrease in mobility of junctional proteins that in triadin appeared to be mediated by its intraluminal region. Together, the data suggest that the organization of specific SR domains results from a process of membrane reorganization accompanied by the establishment of multiple protein–protein interactions with intrinsic and extrinsic cues.
Abnormal cervical cytology is associated with increased nitric oxide release in the uterine cervix
Authors: RAHKOLA PAIVI , MIKKOLA TOMI S. , NIEMINEN PEKKA , YLIKORKALA OLAVI , VAISANEN‐TOMMISKA MERVI
Published: March 2009

Objective. The human uterine cervix is capable of producing nitric oxide (NO). We studied the impact of cytological changes on the release of cervical NO. Design. Population‐based case–control study. Setting. City of Helsinki, Finland. Population. Cervical cytology tests and cervical fluid samples were collected in 297 women. Methods. Cervical cytology tests, classified according to Bethesda criteria, were specifically analyzed for changes typically seen in human papillomavirus (HPV) infection, and the level of NO metabolites (NOx) in cervical fluid was assessed by Griess reaction. Main outcome measures. The difference in cervical fluid NOx between normal and abnormal cytology. Results. Cervical cytology was normal in 219 women and abnormal in 78 women. Among women with abnormal cytology there was both a higher detection rate (89% vs. 71%) and a higher concentration of NOx (median 22.5 μmol/l, 95% CI 14.6–31.9 vs. 11.0 μmol/l, 95% CI 8.0–16.7) compared to women with normal cytology. Age, parity, use of oral contraceptives, phase of the menstrual cycle, or history of miscarriage or termination of early pregnancy were not linked to an increased cervical NOx level. Conclusions. Cervical cell changes (suggestive of HPV infection) are accompanied by an increased release of NO in the human cervix. The significance of this finding remains uncertain, but in theory, increased release of NO could modify the outcome of cervical infection.
The ALP-Enigma Protein ALP-1 Functions in Actin Filament Organization to Promote Muscle Structural Integrity inCaenorhabditis elegans
Authors: Han Hsiao-Fen , Beckerle Mary C.
Published: March 2009

Mutations that affect the Z-disk–associated ALP-Enigma proteins have been linked to human muscular and cardiac diseases. Despite their clear physiological significance for human health, the mechanism of action of ALP-Enigma proteins is largely unknown. In Caenorhabditis elegans, the ALP-Enigma protein family is encoded by a single gene, alp-1; thus C. elegans provides an excellent model to study ALP-Enigma function. Here we present a molecular and genetic analysis of ALP-Enigma function in C. elegans. We show that ALP-1 and α-actinin colocalize at dense bodies where actin filaments are anchored and that the proper localization of ALP-1 at dense bodies is dependent on α-actinin. Our analysis of alp-1 mutants demonstrates that ALP-1 functions to maintain actin filament organization and participates in muscle stabilization during contraction. Reducing α-actinin activity enhances the actin filament phenotype of the alp-1 mutants, suggesting that ALP-1 and α-actinin function in the same cellular process. Like α-actinin, alp-1 also interacts genetically with a connectin/titin family member, ketn-1, to provide mechanical stability for supporting body wall muscle contraction. Taken together, our data demonstrate that ALP-1 and α-actinin function together to stabilize actin filaments and promote muscle structural integrity.
Fibroblast Growth Factor Receptor-1 (FGFR1) Nuclear Dynamics Reveal a Novel Mechanism in Transcription Control
Authors: Dunham-Ems Star M. , Lee Yu-Wei , Stachowiak Ewa K. , Pudavar Haridas , Claus Peter , Prasad Paras N. , Stachowiak Michal K.
Published: March 2009

Nuclear FGFR1 acts as a developmental gene regulator in cooperation with FGF-2, RSK1, and CREB-binding protein (CBP). FRAP analysis revealed three nuclear FGFR1 populations: i) a fast mobile, ii) a slower mobile population reflecting chromatin-bound FGFR1, and iii) an immobile FGFR1 population associated with the nuclear matrix. Factors (cAMP, CBP) that induce FGFR1-mediated gene activation shifted FGFR1 from the nuclear matrix (immobile) to chromatin (slow) and reduced the movement rate of the chromatin-bound population. Transcription inhibitors accelerated FGFR1 movement; the content of the chromatin-bound slow FGFR1 decreased, whereas the fast population increased. The transcriptional activation appears to involve conversion of the immobile matrix-bound and the fast nuclear FGFR1 into a slow chromatin-binding population through FGFR1's interaction with CBP, RSK1, and the high-molecular-weight form of FGF-2. Our findings support a general mechanism in which gene activation is governed by protein movement and collisions with other proteins and nuclear structures.
A modified hyperplane clustering algorithm allows for efficient and accurate clustering of extremely large datasets
Authors: Sharma Ashok , Podolsky Robert , Zhao Jieping , McIndoe Richard A.
Published: March 2009

Motivation: As the number of publically available microarray experiments increases, the ability to analyze extremely large datasets across multiple experiments becomes critical. There is a requirement to develop algorithms which are fast and can cluster extremely large datasets without affecting the cluster quality. Clustering is an unsupervised exploratory technique applied to microarray data to find similar data structures or expression patterns. Because of the high input/output costs involved and large distance matrices calculated, most of the algomerative clustering algorithms fail on large datasets (30 000 + genes/200 + arrays). In this article, we propose a new two-stage algorithm which partitions the high-dimensional space associated with microarray data using hyperplanes. The first stage is based on the Balanced Iterative Reducing and Clustering using Hierarchies algorithm with the second stage being a conventional k-means clustering technique. This algorithm has been implemented in a software tool (HPCluster) designed to cluster gene expression data. We compared the clustering results using the two-stage hyperplane algorithm with the conventional k-means algorithm from other available programs. Because, the first stage traverses the data in a single scan, the performance and speed increases substantially. The data reduction accomplished in the first stage of the algorithm reduces the memory requirements allowing us to cluster 44 460 genes without failure and significantly decreases the time to complete when compared with popular k-means programs. The software was written in C# (.NET 1.1).

Availability: The program is freely available and can be downloaded from http://www.amdcc.org/bioinformatics/bioinformatics.aspx.

Contact:  rmcindoe@mail.mcg.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Comparison of myocardial deformation and velocity dyssynchrony for identification of responders to cardiac resynchronization therapy
Authors: Mele Donato , Toselli Tiziano , Capasso Fabio , Stabile Giuseppe , Piacenti Marcello , Piepoli Massimo , Giatti Sara , Klersy Catherine , Sallusti Luciano , Ferrari Roberto
Published: March 2009

Aims

It is unclear whether myocardial velocity or deformation indices of dyssynchrony are better at predicting response to cardiac resynchronization therapy (CRT). Therefore, two indices of left ventricular (LV) dyssynchrony based on myocardial velocity and deformation were compared to predict success of CRT.

Methods and results

Sixty patients with dilated cardiomyopathy, New York Heart Association class III–IV, LV ejection fraction (EF) ≤35%, QRS >120 ms underwent CRT. The standard deviation of the averaged time‐to‐peak longitudinal negative strain (Tɛ‐SD) and positive systolic velocity (Tv‐SD) of 12 LV segments were calculated before and after 6 months of CRT. Responders were defined at month 6 by ≥20% EF increase and/or ≥15% end‐systolic volume (ESV) decrease with respect to baseline. On univariable analysis, baseline Tɛ‐SD and Tv‐SD were both significantly associated with CRT response; however, the area under the receiver operating characteristic curve was better for Tɛ‐SD. On bivariable analysis, only Tɛ‐SD retained an independent prognostic value for CRT response. Results of the analysis did not change when the logistic models were adjusted for aetiology.

Conclusion

Baseline dyssynchrony of longitudinal myocardial peak deformation (Tɛ‐SD) appears to be better than dyssynchrony of longitudinal myocardial peak systolic velocities (Tv‐SD) for the identification of CRT responders.