bluuebunny/crossref_metadata_2025 huggingface dataset:
Piezoresponse force microscopic study of ferroelectric (1 − x)Pb(Sc1/2Nb1/2)O3 − xPbTiO3 and Pb(Sc1/2Nb1/2)O3 single crystals
Authors: Guo H. Y. , Bing Y. H. , Ye Z.-G.
Published: September 2012

The microscopic piezoelectric response and ferroelectric domain switching in the (001)-oriented rhombohedral piezo-/ferroelectric (1 − x)Pb(Sc1/2Nb1/2)O3 − xPbTiO3 (PSN-PT) and relaxor Pb(Sc1/2Nb1/2)O3 (PSN) single crystals were studied by piezoresponse force microscopy. PSN-PT shows clear domain structures while the domain contrast of PSN is very weak. For PSN-PT, after being fully poled vertically, its lateral domain structure is still composed of a multi-domain state. Both PSN-PT and PSN crystals respond to positive and negative DC field drives through piezoelectricity. However, their poling behaviors are different. For PSN-PT, during successive applications of a positive external electric field, the areas with piezoresponse in phase with the electric field grow at the expense of domains of opposite piezoresponse, implying a domain switching process via sideway motion of domain walls. On the other hand, in the PSN single crystal, the piezoresponse contrast of the alternatively poled area shows a uniformly fading and enhancing pattern, depending on the direction of the polarization component of the domains relative to the external field. While the domain pattern of PSN-PT and its evolution under an external field behave like a normal ferroelectric material, the domain structure and domain evolution process of PSN appear to be abnormal for a ferroelectric, but consistent with the character of a relaxor.
High resolution electron energy loss spectroscopy of clean and hydrogen covered Si(001) surfaces: First principles calculations
Authors: Patterson C. H.
Published: September 2012

Surface phonons, conductivities, and loss functions are calculated for reconstructed (2×1), p(2×2) and c(4×2) clean Si(001) surfaces, and (2×1) H and D covered Si(001) surfaces. Surface conductivities perpendicular to the surface are significantly smaller than conductivities parallel to the surface. The surface loss function is compared to high resolution electron energy loss measurements. There is good agreement between calculated loss functions and experiment for H and D covered surfaces. However, agreement between experimental data from different groups and between theory and experiment is poor for clean Si(001) surfaces. Formalisms for calculating electron energy loss spectra are reviewed and the mechanism of electron energy losses to surface vibrations is discussed.
The Utility of Defocus Blur in Binocular Depth Perception
Authors: Vishwanath Dhanraj
Published: September 2012

The question of whether defocus blur is a quantitative cue for depth perception is a topic of renewed interest. A recent study suggests that relative defocus blur can be used in computing depth throughout the visual field, particularly in regions where disparity loses precision. However, elements of the study's experimental design and theoretical analysis appear to undermine this claim. First, the study did not provide evidence that blur can be used as a quantitative depth cue. It only measured blur discrimination thresholds, not perceived depth from for blur. Second, the study's conceptualization of the complementary use of blur and disparity, and related conjectures, are based on the specific viewing geometry and fixation distance tested. They do not appear to generalize to natural viewing situations and tasks. I suggest a different way in which defocus blur might affect depth perception. Because depth-of-focus blur is a cue to egocentric distance, it could contribute to quantitative depth perception by scaling depth relations specified by other relative depth cues.
Susceptibility of the sheep body louse [Bovicola ovis (Schrank), Phthiraptera: Trichodectidae] to temephos and concentration stability during sheep dipping with a commercial temephos product
Authors: Levot Garry
Published: September 2012

Laboratory bioassays were used to measure the susceptibility of sheep lice [Bovicola ovis (Schrank)] strains that were resistant to pyrethroid or benzoylphenyl urea insect growth regulator insecticides to the organophosphate temephos, the most commonly used wet dipping insecticide. Compared with the reference susceptible strain, only the pyrethroid-resistant ‘Rowena’ strain displayed low level (2.2×) tolerance of temephos. Lice exposed to the minimum lethal concentration of temephos began to be affected within 6–7 h and all had responded to the insecticide within 24 h. In a dipping trial with sheep, the working concentration of temephos in a 5000-L plunge dip operating according to constant replenishment principles remained close to the nominal application rate of 350 mg/L. The ease with which temephos dip concentration was maintained simplified the dipping process. If typical of similar field populations, the absence, or low level of cross-resistance to temephos reported here for insect growth regulator-resistant and pyrethroid-resistant lice, respectively, should make wool producers confident that thorough dipping with temephos according to product label directions should be effective in controlling lice on their sheep.
Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer
Authors: Tucci Paola , Agostini Massimiliano , Grespi Francesca , Markert Elke K. , Terrinoni Alessandro , Vousden Karen H. , Muller Patricia A. J. , Dötsch Volker , Kehrloesser Sebastian , Sayan Berna S. , Giaccone Giuseppe , Lowe Scott W. , Takahashi Nozomi , Vandenabeele Peter , Knight Richard A. , Levine Arnold J. , Melino Gerry
Published: September 2012

p63 inhibits metastasis. Here, we show that p63 (both TAp63 and ΔNp63 isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, and miR-205 is essential for the inhibitory effects of p63 on markers of epithelial–mesenchymal transition (EMT), such as ZEB1 and vimentin. Correspondingly, the inhibitory effect of p63 on EMT markers and cell migration is reverted by anti–miR-205. p53 mutants inhibit expression of both p63 and miR-205, and the cell migration, in a cell line expressing endogenous mutated p53, can be abrogated by pre–miR-205 or silencing of mutated p53. In accordance with this in vitro data, ΔNp63 or miR-205 significantly inhibits the incidence of lung metastasis in vivo in a mouse tail vein model. Similarly, one or both components of the p63/miR-205 axis were absent in metastases or colonized lymph nodes in a set of 218 human prostate cancer samples. This was confirmed in an independent clinical data set of 281 patients. Loss of this axis was associated with higher Gleason scores, an increased likelihood of metastatic and infiltration events, and worse prognosis. These data suggest that p63/miR-205 may be a useful clinical predictor of metastatic behavior in prostate cancer.
TERRITORIAL BORDERS AS INSTITUTIONS
Authors: Müller Andreas
Published: September 2012

In sociological research on territorial borders, theoretical concepts prevail which identify borders with migration control and hence conclude from the contemporary trend to ex-territorialise such controls the dissolution between territories and borders. Such an understanding however prevents to distinguish between different instruments and logics of migration control. Departing from this perspective, the argument is developed that borders are more adequately understood as institutionalised rules about the spatial separation of the exercise of authority. Such a perspective provides first to analytically distinguish between borders in general on the one hand and the specific functions particular borders are designed to fulfil on the other hand. Second, such a concept enables us to address how political and societal actors discover the border as an instrument for realising their interests and hence engage in border politics. Third, the possibility emerges to analyse how processes of globalisation and regional integration change the political perception and thereby the political regulation of borders' functions.
Dependent Children and Women's Sickness Absence in the EU Countries and Norway
Authors: Mastekaasa Arne
Published: September 2012

Previous research has yielded quite varying results with regard to the relationship between children and women's sickness absence from work. This study examines the issue using data from the EU Labour Surveys. Cross-sectional data from 2005 covering 23 EU countries plus Norway are used. The data are analysed by means of logistic regression with control for country, age, working hours and socio-economic status. For married/cohabiting women, there is a quite consistent tendency for dependent children to be associated with lower sickness absence. A single young child is, however, related to higher sickness absence in some analyses, suggesting that the transition to parenthood may be stressful. Single mothers do not in general have higher sickness absence than their married/cohabiting counterparts. The tendency toward lower sickness absence in most groups of married/cohabiting mothers is likely to be due to selection to some extent, but also to favourable role accumulation effects.
The implicit learning of metrical and nonmetrical temporal patterns
Authors: Schultz Benjamin G. , Stevens Catherine J. , Keller Peter E. , Tillmann Barbara
Published: September 2012

Implicit learning (IL) occurs unintentionally. IL of temporal patterns has received minimal attention, and results are mixed regarding whether IL of temporal patterns occurs in the absence of a concurrent ordinal pattern. Two experiments examined the IL of temporal patterns and the conditions under which IL is exhibited. Experiment 1 examined whether uncertainty of the upcoming stimulus identity obscures learning. Based on probabilistic uncertainty, it was hypothesized that stimulus-detection tasks are more sensitive to temporal learning than multiple-alternative forced-choice tasks because of response uncertainty in the latter. Results demonstrated IL of metrical patterns in the stimulus-detection but not the multiple-alternative task. Experiment 2 investigated whether properties of rhythm (i.e., meter) benefit IL using the stimulus-detection task. The metric binding hypothesis states that metrical frameworks guide attention to periodic points in time. Based on the metric binding hypothesis, it was hypothesized that metrical patterns are learned faster than nonmetrical patterns. Results demonstrated learning of metrical and nonmetrical patterns but metrical patterns were not learned more readily than nonmetrical patterns. However, abstraction of a metrical framework was still evident in the metrical condition. The present study shows IL of auditory temporal patterns in the absence of an ordinal pattern.
Your words are my words: Effects of acting together on encoding
Authors: Eskenazi Terry , Doerrfeld Adam , Logan Gordon D. , Knoblich Guenther , Sebanz Natalie
Published: September 2012

Social influences on action and memory are well established. However, it is unknown how acting together affects the incidental encoding of information. The present study asked whether coactors encode information that is relevant to a partner's task, but irrelevant to their own task. In Experiment 1, participants performed a categorization task alone and together, followed by a surprise free recall test where they were asked to recall items from the categorization task. Recall was better not only for items that participants had responded to themselves, but also for items that their coactor had responded to, than for items that had not required a response. The same results were found in Experiment 2, even though financial incentives motivated participants to only encode words they had responded to themselves. Together, the findings suggest that performing tasks together can modulate how information relevant to coactors is processed. Shared task representations may act as a vehicle for establishing shared memories.
Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis
Authors: Wandke Cornelia , Barisic Marin , Sigl Reinhard , Rauch Veronika , Wolf Frank , Amaro Ana C. , Tan Chia H. , Pereira Antonio J. , Kutay Ulrike , Maiato Helder , Meraldi Patrick , Geley Stephan
Published: September 2012

Chromokinesins are microtubule plus end–directed motor proteins that bind to chromosome arms. In Xenopus egg cell-free extracts, Xkid and Xklp1 are essential for bipolar spindle formation but the functions of the human homologues, hKID (KIF22) and KIF4A, are poorly understood. By using RNAi-mediated protein knockdown in human cells, we find that only co-depletion delayed progression through mitosis in a Mad2-dependent manner. Depletion of hKID caused abnormal chromosome arm orientation, delayed chromosome congression, and sensitized cells to nocodazole. Knockdown of KIF4A increased the number and length of microtubules, altered kinetochore oscillations, and decreased kinetochore microtubule flux. These changes were associated with failures in establishing a tight metaphase plate and an increase in anaphase lagging chromosomes. Co-depletion of both chromokinesins aggravated chromosome attachment failures, which led to mitotic arrest. Thus, hKID and KIF4A contribute independently to the rapid and correct attachment of chromosomes by controlling the positioning of chromosome arms and the dynamics of microtubules, respectively.
Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1
Authors: Woo Stephanie , Housley Michael P. , Weiner Orion D. , Stainier Didier Y.R.
Published: September 2012

Embryo morphogenesis is driven by dynamic cell behaviors, including migration, that are coordinated with fate specification and differentiation, but how such coordination is achieved remains poorly understood. During zebrafish gastrulation, endodermal cells sequentially exhibit first random, nonpersistent migration followed by oriented, persistent migration and finally collective migration. Using a novel transgenic line that labels the endodermal actin cytoskeleton, we found that these stage-dependent changes in migratory behavior correlated with changes in actin dynamics. The dynamic actin and random motility exhibited during early gastrulation were dependent on both Nodal and Rac1 signaling. We further identified the Rac-specific guanine nucleotide exchange factor Prex1 as a Nodal target and showed that it mediated Nodal-dependent random motility. Reducing Rac1 activity in endodermal cells caused them to bypass the random migration phase and aberrantly contribute to mesodermal tissues. Together, our results reveal a novel role for Nodal signaling in regulating actin dynamics and migration behavior, which are crucial for endodermal morphogenesis and cell fate decisions.
Neutrophil extracellular traps: Is immunity the second function of chromatin?
Authors: Brinkmann Volker , Zychlinsky Arturo
Published: September 2012

Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed “NETosis.” Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.
Multiferroic behaviour and the magneto-dielectric effect in Bi5FeTi3O15 thin films
Authors: Sun Hui , Lu Xiaomei , Su Jie , Xu Tingting , Ju Changcheng , Huang Fengzhen , Zhu Jinsong
Published: September 2012

Thin films of Fe-containing the Aurivillius phase Bi5FeTi3O15 (BFTO) were successfully prepared by chemical solution deposition. The microstructure, ferroelectric behaviours, magnetic properties and the magneto-dielectric effect were investigated systematically at room temperature (RT). A definite hysteresis loop of the BFTO film was obtained with the remanent polarization (2P
r) ∼ 43.3 µC cm−2 under an electric field of 300 kV cm−1. To exclude the contribution of the leakage current to polarization, we studied the frequency dependence of hysteresis loops in the BFTO thin film and made positive-up–negative-down measurements. These results indicated the intrinsic ferroelectricity in the present BFTO film and it was supported by the ε–V curve. Furthermore, a weak ferromagnetism with an in-plane saturated magnetization (M
s) of ∼ 1.7 emu cm−3 was also observed in the BFTO film, which may have originated from the Fe2+–O–Fe3+ nanocluster and the F-centre exchange (FCE) mechanism. Therefore, the ferromagnetism could be considered as in nanoregions. More importantly, the magneto-dielectric effect was found with a magneto-dielectric coefficient of ∼−2.8% at a frequency of 100 kHz at RT. The probable origins of magnetic anisotropy and the magneto-dielectric effect were discussed. All these results demonstrated the RT multiferroic behaviour of the BFTO film.
Shear-induced Reynolds stress at the edge of L-mode tokamak plasmas
Authors: Fedorczak N. , Diamond P.H. , Tynan G. , Manz P.
Published: September 2012

The turbulent flux of momentum—or Reynolds stress—is a mechanism responsible for the generation of sheared flow by turbulence. The structure of the flux-surface-averaged stress

is investigated in the edge region of an L-mode tokamak plasma. The stress induced by the perpendicular tilting of ballooning modes is considered. In addition to the tilting by the E × B flow shear, which is a negative viscosity effect, a magnetic-shear-induced Reynolds stress—called

-residual stress—arises as a consequence of a residual spatial tilting of ballooning modes by the magnetic shear in a poloidally up–down asymmetric magnetic geometry. A model is derived in the weak flow shear regime under the approximation of circular flux surfaces. The amplitude of this residual stress is of the order of the square of the radial velocity fluctuations in the scrape-off layer (SOL), and in the immediate radial vicinity of the separatrix if an X-point exists. Its amplitude drops rapidly to zero towards the plasma core, thus appearing as a source of transverse rotation at the interface. Its non-linear dependence on the electric shear is discussed in the context of the weak electric shear effect on the poloidal shape of the ballooning envelope. The local

-residual stress is non-uniform poloidally and changes sign according to the up/down position of SOL end-plates with respect to the ∇B × B direction. The electric- and magnetic-shear-induced stresses are then included in a flux-surface-averaged 1D model of mean flow conservation at the plasma edge, including the SOL volume. In L-mode weak shear regimes, it is shown that changing the plasma geometry from ∇B × B away from the divertor to ∇B × B towards the divertor approximately doubles the electric shear strength inside the separatrix, as reported in experiments. This shear-induced stress also enters the toroidal momentum balance, where it appears as a significant source of momentum in the immediate vicinity of the separatrix. Balanced by the toroidal viscosity only, it can sustain toroidal flow gradients of the order of a km s−1 cm−1 at the separatrix, with a sign also dependent on the plasma geometry. These momentum sources arising from symmetry breaking at the boundary of the confined region may explain why low to high mode power thresholds are lower in favourable than unfavourable configurations, and may be important for the issue of optimal plasma shapes with respect to edge intrinsic shear.
Study of fast-ion transport induced by fishbones on JET
Authors: Perez von Thun C. , Salmi A. , Perona A. , Sharapov S.E. , Pinches S.D. , Popovichev S. , Conroy S. , Kiptily V.G. , Brix M. , Cecconello M. , Johnson T.
Published: September 2012

The impact of fishbone oscillations onto a confined fast-ion population is simulated for a JET plasma and benchmarked against experiment quantitatively with the help of neutron rate measurements. The transient drops in volume integrated neutron emission are found to be mainly caused by the spatial redistribution of the (neutral beam injected) fast-ion population confined in the plasma rather than by fast-ion loss. The simulations yield a quadratic dependence of the neutron drop on the fishbone amplitude. It is found that the simulations are able to correctly reproduce the magnitude of the experimentally observed drop in volume integrated neutron emission to within a factor 2. Furthermore, frequency chirping is found to be important. Omitting the fishbone frequency chirp in the simulations reduces the magnitude of the neutron rate drop (and hence fast-ion redistribution) to about half its original value.
Simulations of fast ion wall loads in ASDEX Upgrade in the presence of magnetic perturbations due to ELM-mitigation coils
Authors: Asunta O. , Äkäslompolo S. , Kurki-Suonio T. , Koskela T. , Sipilä S. , Snicker A. , García-Muñoz M.
Published: September 2012

The effect of ASDEX Upgrade (AUG) edge localized mode (ELM)-mitigation coils on fast ion wall loads was studied with the fast particle following Monte Carlo code ASCOT. Neutral beam injected particles were simulated in two AUG discharges both in the presence and in the absence of the magnetic field perturbation induced by the eight newly installed in-vessel coils. In one of the discharges (#26476) beams were applied individually, making it a useful basis for investigating the effect of the coils on different beams. However, no ELM mitigation was observed in #26476, probably due to the low plasma density. Therefore, another discharge (#26895) demonstrating clear ELM mitigation was also studied. The magnetic perturbation due to the in-vessel coils has a significant effect on the fast particle confinement, but only when total magnetic field, B
tot, is low. When B
tot was high, the perturbation did not increase the losses, but merely resulted in redistribution of the wall power loads. Hence, it seems to be possible to achieve ELM mitigation using in-vessel coils, while still avoiding increased fast ion losses, by simply using a strong B
tot. Preliminary comparisons between simulated and experimental fast ion lost detector signals show a reasonable correspondence.
Status of the JET Faraday cup lost alpha particle diagnostic KA-2
Authors: Cecil F.E. , Kiptily V. , Darrow D.S. , Murari A.
Published: September 2012

We review the operational status and present a few recent results from the JET lost alpha particle diagnostic KA2. We summarize the results of our study of the correlation between KA2 signals and JET magnetic fields and the correlation between KA2 signals and the scintillator-based lost alpha probe KA3. In addition we quantify the relative insensitivity of the diagnostic to intense neutron and gamma ray background radiation fields and our observations of the electro-mechanical noise in the diagnostics signals. We present recent observations carried out during the 2011 JET campaign following the installation of the beryllium ITER-like wall. These observations include lost energetic deuterons during both ion-cyclotron and neutral beam heated plasmas; in particular we have measured relatively intense fluxes of energetic particles during sawtooth plasmas.
Recent advances in nuclear magnetic resonance quantum information processing
Authors: Criger Ben , Passante Gina , Park Daniel , Laflamme Raymond
Published: September 2012

Quantum information processors have the potential to drastically change the way we communicate and process information. Nuclear magnetic resonance (NMR) has been one of the first experimental implementations of quantum information processing (QIP) and continues to be an excellent testbed to develop new QIP techniques. We review the recent progress made in NMR QIP, focusing on decoupling, pulse engineering and indirect nuclear control. These advances have enhanced the capabilities of NMR QIP, and have useful applications in both traditional NMR and other QIP architectures.
Geometric aspects of composite pulses
Authors: Ichikawa Tsubasa , Bando Masamitsu , Kondo Yasushi , Nakahara Mikio
Published: September 2012

Unitary operations acting on a quantum system must be robust against systematic errors in control parameters for reliable quantum computing. Composite pulse technique in nuclear magnetic resonance realizes such a robust operation by employing a sequence of possibly poor-quality pulses. In this study, we demonstrate that two kinds of composite pulses—one compensates for a pulse length error in a one-qubit system and the other compensates for a
J
-coupling error in a two-qubit system—have a vanishing dynamical phase and thereby can be seen as geometric quantum gates, which implement unitary gates by the holonomy associated with dynamics of cyclic vectors defined in the text.
Experimental study of quantum simulation for quantum chemistry with a nuclear magnetic resonance simulator
Authors: Lu Dawei , Xu Nanyang , Xu Boruo , Li Zhaokai , Chen Hongwei , Peng Xinhua , Xu Ruixue , Du Jiangfeng
Published: September 2012

Quantum computers have been proved to be able to mimic quantum systems efficiently in polynomial time. Quantum chemistry problems, such as static molecular energy calculations and dynamical chemical reaction simulations, become very intractable on classical computers with scaling up of the system. Therefore, quantum simulation is a feasible and effective approach to tackle quantum chemistry problems. Proof-of-principle experiments have been implemented on the calculation of the hydrogen molecular energies and one-dimensional chemical isomerization reaction dynamics using nuclear magnetic resonance systems. We conclude that quantum simulation will surpass classical computers for quantum chemistry in the near future.
Implementing quantum logic gates with gradient ascent pulse engineering: principles and practicalities
Authors: Rowland Benjamin , Jones Jonathan A.
Published: September 2012

We briefly describe the use of gradient ascent pulse engineering (GRAPE) pulses to implement quantum logic gates in nuclear magnetic resonance quantum computers, and discuss a range of simple extensions to the core technique. We then consider a range of difficulties that can arise in practical implementations of GRAPE sequences, reflecting non-idealities in the experimental systems used.
Storage of quantum coherences as phase-labelled local polarization in solid-state nuclear magnetic resonance
Authors: Franzoni María Belén , Acosta Rodolfo H. , Pastawski Horacio M. , Levstein Patricia R.
Published: September 2012

Nuclear spins are promising candidates for quantum information processing because their good isolation from the environment precludes the rapid loss of quantum coherence. Many strategies have been developed to further extend their decoherence times. Some of them make use of decoupling techniques based on the Carr–Purcell and Carr–Purcell–Meiboom–Gill pulse sequences. In many cases, when applied to inhomogeneous samples, they yield a magnetization decay much slower than that of the Hahn echo. However, we have proved that these decays cannot be associated with longer decoherence times, as coherences remain frozen. They result from coherences recovered after their storage as local polarization and thus they can be used as memories. We show here how this freezing of the coherent state, which can subsequently be recovered after times longer than the natural decoherence time of the system, can be generated in a controlled way with the use of field gradients. A similar behaviour of homogeneous samples in inhomogeneous fields is demonstrated. It is emphasized that the effects of inhomogeneities in solid-state nuclear magnetic resonance, independently of their origin, should not be disregarded, as they play a crucial role in multipulse sequences.
Control aspects of quantum computing using pure and mixed states
Authors: Schulte-Herbrüggen Thomas , Marx Raimund , Fahmy Amr , Kauffman Louis , Lomonaco Samuel , Khaneja Navin , Glaser Steffen J.
Published: September 2012

Steering quantum dynamics such that the target states solve classically hard problems is paramount to quantum simulation and computation. And beyond, quantum control is also essential to pave the way to quantum technologies. Here, important control techniques are reviewed and presented in a unified frame covering quantum computational gate synthesis and spectroscopic state transfer alike. We emphasize that it does not matter whether the quantum states of interest are pure or not. While pure states underly the design of quantum circuits, ensemble mixtures of quantum states can be exploited in a more recent class of algorithms: it is illustrated by characterizing the Jones polynomial in order to distinguish between different (classes of) knots. Further applications include Josephson elements, cavity grids, ion traps and nitrogen vacancy centres in scenarios of closed as well as open quantum systems.
Dependability Modeling and Assessment in UML-Based Software Development
Authors: Bernardi Simona , Merseguer José , Petriu Dorina C.
Published: September 2012

Assessment of software nonfunctional properties (NFP) is an important problem in software development. In the context of model-driven development, an emerging approach for the analysis of different NFPs consists of the following steps: (a) to extend the software models with annotations describing the NFP of interest; (b) to transform automatically the annotated software model to the formalism chosen for NFP analysis; (c) to analyze the formal model using existing solvers; (d) to assess the software based on the results and give feedback to designers. Such a modeling→analysis→assessment approach can be applied to any software modeling language, be it general purpose or domain specific. In this paper, we focus on UML-based development and on the dependability NFP, which encompasses reliability, availability, safety, integrity, and maintainability. The paper presents the profile used to extend UML with dependability information, the model transformation to generate a DSPN formal model, and the assessment of the system properties based on the DSPN results.
Corneal Pocket Assay in Rabbits: Figure 1.
Authors: Jain Rakesh K. , Munn Lance L. , Fukumura Dai
Published: September 2012

The anterior chamber of the eye is a natural site for observing tumor growth, and implantation in a corneal pocket can be used for this purpose. This protocol describes the corneal pocket assay in rabbits. Because of the 3D nature of vessel growth, it is difficult to quantify the vascular response except in the early stages when the vessel length/number can be assessed. The assay can be used for mice with modification. Although it is less expensive to use rats/mice compared with rabbits, surgery on smaller eyes is more difficult. Furthermore, because the rat/mouse cornea is thinner than the rabbit’s, the three-dimensional (3D) growth of vessels is even more limited.
Remission of refractory Crohn's disease by high‐dose cyclophosphamide and autologous peripheral blood stem cell transplantation
Authors: Hasselblatt P. , Drognitz K. , Potthoff K. , Bertz H. , Kruis W. , Schmidt C. , Stallmach A. , Schmitt‐Graeff A. , Finke J. , Kreisel W.
Published: September 2012

Background

Despite advances in immunosuppressive therapy, up to 10% of patients with severe Crohn's disease (CD) remain refractory to conventional treatment. Limited evidence from pilot trials suggests that high‐dose immunosuppression and autologous peripheral blood stem cell transplantation (autoPBSCT) may induce remission in these patients, but there is substantial controversy regarding the safety and efficacy of this approach.

Aim

To address this issue, a monocentre phase I/II trial of autoPBSCT was performed in patients with refractory CD in our hospital.

Methods

Here, we report on the outcome of 12 patients with refractory CD treated with autoPBSCT. Briefly, CD34+‐selected PBSCs were harvested after mobilisation therapy with cyclophosphamide and granulocyte‐colony stimulating factor. Later, immunoablative conditioning therapy with high‐dose cyclophosphamide followed by autoPBSCT was applied and clinical and endoscopic responses were analysed after a mean follow‐up of 3.1 years (range 0.5–10.3 years).

Results

PBSC harvest following mobilisation chemotherapy was successful in 11/12 patients and resulted in a clinical and endoscopic improvement in 7/12 patients. Subsequent conditioning and autoPBSCT were performed in nine patients and were relatively well tolerated. Among those, five patients achieved a clinical and endoscopic remission within 6 months after autoPBSCT. However, relapses occurred in 7/9 patients during follow‐up, but disease activity could be controlled by low‐dose corticosteroids and conventional immunosuppressive therapy.

Conclusion

Immunoablation by cyclophosphamide and autologous peripheral blood stem cell transplantation is safe and effective to induce remission of refractory Crohn's disease, and should be further evaluated in randomised controlled trials.
Identification of Purple Acid Phosphatase Inhibitors by Fragment‐Based Screening: Promising New Leads for Osteoporosis Therapeutics
Authors: Feder Daniel , Hussein Waleed M. , Clayton Daniel J. , Kan Meng‐Wei , Schenk Gerhard , McGeary Ross P. , Guddat Luke W.
Published: September 2012

Purple acid phosphatases are metalloenzymes found in animals, plants and fungi. They possess a binuclear metal centre to catalyse the hydrolysis of phosphate esters and anhydrides under acidic conditions. In humans, elevated purple acid phosphatases levels in sera are correlated with the progression of osteoporosis and metabolic bone malignancies, making this enzyme a target for the development of new chemotherapeutics to treat bone‐related illnesses. To date, little progress has been achieved towards the design of specific and potent inhibitors of this enzyme that have drug‐like properties. Here, we have undertaken a fragment‐based screening approach using a 500‐compound library identifying three inhibitors of purple acid phosphatases with Ki values in the 30–60 μm range. Ligand efficiency values are 0.39–0.44 kcal/mol per heavy atom. X‐ray crystal structures of these compounds in complex with a plant purple acid phosphatases (2.3–2.7 Å resolution) have been determined and show that all bind in the active site within contact of the binuclear centre. For one of these compounds, the phenyl ring is positioned within 3.5 Å of the binuclear centre. Docking simulations indicate that the three compounds fit into the active site of human purple acid phosphatases. These studies open the way to the design of more potent and selective inhibitors of purple acid phosphatases that can be tested as anti‐osteoporotic drug leads.
Synthesis and Biological Evaluation of Coumarin Derivatives as Inhibitors of Mycobacterium bovis (BCG)
Authors: Rezayan Ali Hossein , Azerang Parisa , Sardari Soroush , Sarvary Afshin
Published: September 2012

The coumarin compounds are an important class of biologically active molecules, which have attractive caught the attention of many organic and medicinal chemists, due to potential pharmaceutical implications and industrial applications. We herein report the one‐pot procedure for the efficient synthesis of coumarin derivatives using commercially available substrates via isocyanide‐based multicomponent condensation reactions. These compounds were evaluated for anti‐mycobacterium activity against Mycobacterium bovis (Bacillus Calmette–Guerin). The preliminary results indicated that all of the tested compounds showed relatively good activity against the test organism. The compounds 7e, 7l, and 7m showed high anti‐tuberculosis activity.
Cost‐effectiveness analysis of sacral neuromodulation for faecal incontinence in the Netherlands
Authors: van Wunnik B. P. W. , Visschers R. G. J. , van Asselt A. D. I. , Baeten C. G. M. I.
Published: September 2012

Aim  Sacral neuromodulation (SNM) plays a major part in the algorithm of management of faecal incontinence, but there are limited data on its cost‐effectiveness. This study aimed to analyse this and the quality‐adjusted life‐years (QALYs) associated with two different treatment algorithms. The first (SNM−) included use of an artificial sphincter [dynamic graciloplasty (DGP) (50%) and artificial bowel sphincter (ABS) (50%)]. The second (SNM+) included SNM (80% of cases) and artificial sphincter (DGP 10%; ABS 10%) The incidence of sphincteroplasty was assumed to be equal in both algorithms.

Method  A Markov model was developed. A hypothetical cohort of patients was run through both strategies of the model. A mailed EuroQoL‐5D questionnaire was used to determine health‐related quality of life. Costs were reproduced from the Maastricht University Medical Centre prospective faecal incontinence database. The time scale of the analysis was 5 years.

Results  The former treatment protocol cost €22 651 per patient and the latter, after the introduction of SNM, cost €16 473 per patient. The former treatment protocol resulted in a success rate of 0.59 after 5 years, whereas with the introduction of SNM this was 0.82. Adhering to the former treatment protocol yielded 4.14 QALYs and implementing the latter produced 4.21 QALYs.

Conclusion  The study demonstrated that introducing SNM in the surgical management algorithm for faecal incontinence was both more effective and less costly than DGP or ABS without SNM. This justifies adequate funding for SNM for patients with faecal incontinence.
Metachronous colorectal cancer risk in patients with a moderate family history
Authors: Newton K. F. , Green K. , Walsh S. , Lalloo F. , Hill J. , Evans D. G. R.
Published: September 2012

Aim  Lifetime risk of a metachronous colorectal cancer (mCRC) is 0.6–3% following sporadic colorectal cancer (CRC) and 15–26% in Lynch syndrome. The lifetime incidence of CRC in individuals with moderate familial risk is 8–17%. Risk of mCRC is unknown.

Method  A retrospective longitudinal study of the Regional Familial CRC Registry was performed. Patients who had at least one CRC were categorized as follows: moderate risk (n = 383), Lynch syndrome (n = 528) and average (population) risk (n = 409). The Kaplan–Meier estimate (1‐KM) and the cumulative incidence function were used to calculate the risk of mCRC. The 1‐KM gives the risk for individuals remaining at risk (alive) at a given time point and thus is useful for counselling. The cumulative incidence function gives the risk for the whole population.

Results  The 1‐KM and the cumulative incidence function demonstrated that the risk of mCRC was significantly higher in moderate‐risk patients compared with average (population)‐risk patients (1‐KM, P = 0.008; cumulative incidence function, P = 0.00097). However, the risk of mCRC was higher in patients with Lynch syndrome than in moderate‐risk or average (population)‐risk patients. The 1‐KM in moderate‐risk patients was 2.7%, 6.3% and 23.5% at 5, 10 and 20 years, respectively. In average (population)‐risk patients, the 1‐KM was 1.3%, 3.1% and 7.0% at 5, 10 and 20 years, and the cumulative incidence function was 0.3%, 0.6% and 2.4% at the same time points, respectively.

Conclusion  These data indicate that the risk of mCRC is significantly higher in patients with a moderate family history of CRC than in those with an average (population) risk. This justifies proactive lifelong surveillance.
Epileptic seizures in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence, risk factors, and survival rates
Authors: Zhang Xiao‐hui , Xu Lan‐ping , Liu Dai‐hong , Chen Huan , Han Wei , Chen Yu‐hong , Wang Feng‐rong , Wang Jing‐zhi , Wang Yu , Zhao Ting , Chen Yao , Fu Hai‐xia , Liu Kai‐yan , Huang Xiao‐jun
Published: September 2012

The incidence of epileptic seizures among allogeneic hematopoietic stem cell transplant (allo‐HSCT) patients has been poorly described. No report has systematically studied epilepsy's possible causes, risk factors, and effect on prognosis among allo‐HSCT patients. We retrospectively examined data from 1461 patients who underwent allo‐HSCT within the past 6.5 yr at the Institute of Hematology and People's Hospital, Peking University. The cumulative incidence of all epileptic seizure complications was 7.1%. Of the 79 transplant patients who had epileptic seizures, 3 (3.8%) experienced a seizure during the conditioning stage, 52 (65.8%) between day 0 and day 100, 20 (25.3%) from day 100 to the first year, and 4 (5.1%) after the first year. Multivariate regression analysis identified the age of the recipient as (≤18 yr) (p < 0.001), donor type (p = 0.004), graft versus host disease (aGVHD) (p = 0.018), and hyponatremia (p = 0.003) as independent risk factors for epileptic seizures among allo‐HSCT patients. The median survival time of patients with epileptic seizures was 246 d after transplantation (ranging between 18 and 2170 d). Survival after one yr and 6.5 yr was significantly reduced in patients who developed epileptic seizure complications compared with those who did not (57.2% vs. 75.7% at one yr, p = 0.015, and 31.1% vs. 71.4% at five yr, p < 0.001). Of the 79 patients who experienced epileptic seizure complications, 53.2% died (n = 42). The survival rate of these patients was relatively low, and cerebrovascular disorders or central nervous system infection‐related epileptic seizures usually resulted in a high mortality and poor prognosis. A patient transplantation age which is younger than 18 yr, related mismatched transplants, aGVHD, and hyponatremia are risk factors for epileptic seizures in allo‐HSCT recipients. Epileptic seizures among allo‐HSCT patients are associated with a poor prognosis.
Early findings of prospective anti‐HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience
Authors: Mujtaba Muhammad A. , Fridell Jonathan A. , Higgins Nancy , Sharfuddin Asif A. , Yaqub Muhammad S. , Kandula Praveen , Chen Jeanne , Mishler Dennis P. , Lobashevsky Andrew , Book Benita , Powelson John , Taber Tim E.
Published: September 2012

The significance of donor‐specific antibodies (DSA) is not well known in the setting of pancreas transplantation. Since December 2009, we prospectively followed pancreas transplant patients with single‐antigen‐luminex‐bead testing at one, two, three, six, and then every six months for the first two yr. Thirty‐five of the 92 patients that underwent pancreas transplantation (13 pancreas‐alone [PTA], 20 with a kidney [SPK], and two after a kidney [PAK]) agreed to participate in study. Median age at transplant was 45 yr and follow‐up was 23 months. Majority were Caucasian (n = 33) and male (n = 18). Rabbit anti‐thymocyte globulin induction was used. Median HLA‐mismatch was 4.2 ± 1.1. Eight patients (7SPK, 1PAK) developed post‐transplant DSA at median follow‐up of 76 d (26–119), 1 SPK had pre‐formed DSA. Seven patients had both class I and class II DSA, one with class I and one with class II only. Mean peak class I DSA‐MFI was 3529 (±1456); class II DSA‐MFI was 5734 (±3204) whereas cumulative DSA MFI (CI + CII) was 9264 (±4233). No difference was observed in the patient and donor demographics among patients with and without DSA. One patient in non‐DSA group developed acute cellular rejection of pancreas. From our data it appears that post‐transplant DSA in pancreas allograft recipients may not impact the early‐pancreatic allograft outcomes. The utility of prospective DSA monitoring in pancreatic transplant patients needs further evaluation and long‐term follow‐up.
Use of the ThinPrep Imaging System for internal quality control of cervical cytology
Authors: Heard T. , Chandra A. , Culora G. , Gupta S. S. , Herbert A. , Morgan M.
Published: September 2012

T. Heard, A. Chandra, G. Culora, S.S. Gupta, A. Herbert and M. Morgan  Use of the ThinPrep Imaging System for internal quality control of cervical cytology

Objective:  To audit the use of the ThinPrep Imaging System (TIS) for internal quality control (IQC) in the place of rapid review (RR), and to compare its performance with routine primary screening.

Method:  During 9 months, 16 462 ThinPrep slides were processed by TIS. Slides were initially reviewed using the TIS review scope, as recommended by the manufacturer: 22 fields of view were observed and, if considered abnormal, a full microscopic review was conducted using the review scope. Different biomedical scientists (BMSs), working on each procedure in rotation, performed batches of TIS‐assisted quality control and routine primary screening independently on unmarked slides. Any slides with abnormalities detected by either method were referred to a consultant pathologist or advanced BMS practitioner for a final report. TIS results were compared with both previous records of RR and routine primary screening carried out on the same slides. We used the UK terminology in which ‘dyskaryosis’ is equivalent to squamous intraepithelial lesion (SIL) and borderline to atypical (including squamous and glandular cells).

Results:  TIS preview detected significantly more high‐grade dyskaryosis compared with RR during the previous 4 years: 2.0–4.2 compared with 0.1–1.8 detected per 1000 slides (P = 0.0001). TIS and routine screening were equivalent in sensitivity and specificity for the final cytology result, but BMSs were significantly more likely to classify slides as dyskaryotic rather than borderline when using TIS compared with routine screening. Referrals for potentially high‐grade abnormalities detected by TIS‐assisted IQC alone found 28 biopsies of at least cervical intraepithelial neoplasia grade 2 (CIN2+), whereas 15 CIN2+ biopsies were found on routine screening but missed using TIS. There was no significant change in the rates of inadequate tests, high‐ or low‐grade cytological abnormalities, or positive predictive value for CIN2+ when TIS was in use.

Conclusions:  Screening with TIS was more sensitive than RR for IQC, providing a rescreening method equivalent to routine primary screening in overall accuracy.
Role of DNA methylation in growth and differentiation in Physcomitrella patens and characterization of cytosine DNA methyltransferases
Authors: Malik Garima , Dangwal Meenakshi , Kapoor Sanjay , Kapoor Meenu
Published: September 2012

Epigenetic mechanisms such as DNA methylation are known to regulate important developmental processes in higher eukaryotes. However, little is known about the necessity and role of this process in early land plants. Using the methyltransferase (MTase) inhibitor zebularine (1‐(β‐d‐ribofuranosyl)‐1,2‐dihydropyrimidine‐2‐one), the impact of loss of genome‐wide methylation on the overall development in Physcomitrella patens was analyzed. It is observed that various aspects of growth and differentiation during gametophyte development become aberrant. A search for the core molecular components of methylation machinery, cytosine DNA MTases, revealed the presence of seven loci in the P. patens genome. Five of the loci code for MTases that are similar to corresponding proteins in higher plants, while two MTases appear specific to P. patens and are closely related to human DNMT3a and DNMT3b, respectively. These proteins possess all the conserved catalytic motifs characteristic of MTases and a domain of unknown function, DUF3444. Association of these highly conserved motifs with a DUF has not been reported in any of the MTases known so far. All the seven genes are differentially but ubiquitously expressed in gametophytes at low levels. Subcellular localization of GFP‐fused proteins shows patterns of distribution that can be correlated with their putative cellular functions. This work bridges the knowledge of MTases in P. patens and makes this simple model plant accessible for studies on epigenetic aspects that remain intractable in higher plants.