bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing pulsed‐chemical exchange saturation transfer imaging sequences
Authors: Zu Zhongliang , Li Ke , Janve Vaibhav A. , Does Mark D. , Gochberg Daniel F.
Published: March 2011

Chemical exchange saturation transfer (CEST) provides a new imaging contrast mechanism sensitive to labile proton exchange. Pulsed‐CEST imaging is better suited to the hardware constraints on clinical imaging systems when compared with traditional continuous wave‐CEST imaging methods. However, designing optimum pulsed‐CEST imaging sequences entails complicated and time‐consuming numerical integrations. In this work, a simplified and computationally efficient technique is provided to optimize the pulsed‐CEST imaging sequence. An analysis was performed of the optimal average irradiation power and the optimal irradiation flip angle as a function of the acquisition parameters and sample properties in both a two‐pool model and a three‐pool model of endogenous amine exchange. Key simulated and experimental results based on a creatine/agar tissue phantom show that (1) the average irradiation power is a more meaningful sequence metric than is the average irradiation field amplitude, (2) the optimal average powers for continuous wave and pulsed‐CEST imaging are approximately equal to each other for a relevant range of solute frequency offsets, exchange rates, and concentrations, (3) an irradiation flip angle of 180° is optimal or near optimal, independent of the other acquisition parameters and the sample properties, and (4) higher duty cycles yield higher CEST contrast. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Generation of an atlas of the proximal femur and its application to trabecular bone analysis
Authors: Carballido‐Gamio Julio , Folkesson Jenny , Karampinos Dimitrios C. , Baum Thomas , Link Thomas M. , Majumdar Sharmila , Krug Roland
Published: March 2011

Automatic placement of anatomically corresponding volumes of interest and comparison of parameters against a standard of reference are essential components in studies of trabecular bone. Only recently, in vivo MR images of the proximal femur, an important fracture site, could be acquired with high‐spatial resolution. The purpose of this MRI trabecular bone study was two‐fold: (1) to generate an atlas of the proximal femur to automatically place anatomically corresponding volumes of interest in a population study and (2) to demonstrate how mean models of geodesic topological analysis parameters can be generated to be used as potential standard of reference. Ten females were used to generate the atlas and geodesic topological analysis models, and 10 females were used to demonstrate the atlas‐based trabecular bone analysis. All alignments were based on three‐dimensional (3D) multiresolution affine transformations followed by 3D multiresolution free‐form deformations. Mean distances less than 1 mm between aligned femora, and sharp edges in the atlas and in fused gray‐level images of registered femora indicated that the anatomical variability was well accommodated and explained by the free‐form deformations. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Humerus Varus in a Subadult Skeleton from the Medieval Graveyard of La Madeleine (Orléans, France)
Authors: Kacki S. , Duneufjardin P. , Blanchard P. , Castex D.
Published: March 2011

The skeleton of a subadult individual from the medieval graveyard of La Madeleine (Orléans, France) exhibits varus deformity of its right humerus. The affected bone is shortened, the diaphysis is angulated and the head is grossly deformed. The skeleton is otherwise normal. Several diagnoses are debated, including mucopolysaccharidoses, thalassemia, infection and trauma, the latter being preferred. The severity of the bone changes suggests that the growth disturbance occurred early in the life of the individual. We therefore suppose that the causative trauma occurred at the time of birth or during the early postnatal period. Copyright © 2011 John Wiley & Sons, Ltd.
A Viscoplastic‐Damage Model for the Lifetime Prediction of Regeneratively Cooled Noozle Structures
Authors: Tini Vivian , Reese Stefanie
Published: March 2011

The cooling channel wall within the combustion chamber of a Reusable Launch Vehicle (RLV) is subjected to severe operating conditions which eventually lead to the damage of the wall. The failure mode is well known as the “dog‐house” effect where the wall becomes thinner and bulges toward the interior of the chamber. Supported by the German Research Foundation, a viscoplastic‐damage model is being developed to enable a realistic description of the material behaviour under extreme cyclic thermomechanical loadings where creep and hardening phenomena might take place. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modelling of growth inhomogeneities in timber structures for realistic computations
Authors: Jenkel Christian , Lang Ronny , Kaliske Michael
Published: March 2011

This contribution discusses the numerical analysis of timber structures by means of the Finite Elements Method. As a naturally grown and fibrous material, wood shows distinctive material directions, which are captured by a cylindrically anisotropic model. Due to the growth conditions of a tree, the fiber course in wooden structural parts can differ. Especially branches, leading to knots, affect the mechanical properties. Therefore, an approach for the modelling of these growth inhomogeneities is presented. For the three‐dimensional determination of the fiber course in the area of the inhomogeneities, an optimization procedure, using the idea of minimization of shear stresses in tree growth, has been developed. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bifurcation of slow motions in a stiff spring pendulum
Authors: Steindl Alois
Published: March 2011

We consider free oscillations of a double pendulum, where one of the pendula is modelled as a very stiff spring. Contrary to a single spring pendulum numerical simulations show an unexpected large influence of the fast longitudinal oscillations on the slow pendulum oscillations even for extremely large values of the stiffness. The transition from the regular motion, which is governed by the dynamics of a rigid double pendulum close to a periodic orbit, to the irregular motion with large contributions from the longitudinal oscillations occurs due to a subcritical symmetry breaking bifurcation of the periodic solution. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Phase‐field modeling of the effect of interfacial energy on pyrolytic carbon morphology in chemical vapor deposition
Authors: Li Aijun , Deutschmann Olaf , Piat Romana , Böhlke Thomas , Tsukrov Igor , Gross Todd
Published: March 2011

A conserved phase‐field model is proposed to investigate the effect of interfacial energy on the morphological evolution of the pyrolytic carbon deposit in chemical vapor deposition. The equilibrium geometry of carbon deposit islands is analytically predicted, of which the contact angle was controlled through the boundary conditions of the phase‐field parameter at the substrate surface according to the Young‐Laplace equation. Simulations of deposit growth are carried out for single and multi island nucleation. It is clarified that the island morphology depends on the magnitude of the interface energy. It is also observed that high interface energy results in large island size fluctuation. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Numerical Studies of the Influence of the Porosity on Macroscopic Elastic Properties of Carbon/Carbon Composites
Authors: Piat R. , Böhlke T. , Deutschmann O. , Dietrich S. , Drach B. , Gebert J.‐M. , Gross T. , Li A. , Reznik B. , Stasiuk G. , Tsukrov I. , Wanner A.
Published: March 2011

Material parameter identification of the carbon/carbon composites was provided using numerical implementation of semi‐analytical methods and FE‐calculations. The distribution of the fibers and pores obtained from microstructural studies is used as input for homogenization schemes for the determination of the effective elastic constants. The predictions are compared to experimental results. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Application of the semy‐analytical micromechanical methods for optimization of the elastic response of metal‐ceramic composites
Authors: Piat Romana , Sinchuk Yuriy , Vasoya Manishkumar
Published: March 2011

Metal‐ceramic composites produced by melt infiltration of the ceramic preform were studied. The ceramic preform of these materials is manufactured through freeze‐casting process and the microstructure can be presented as distribution of the lamellar domains. Micromechanical models were used for the calculation of the effective elastic properties of the domains. The minimum compliance problem was solved for sample subjected to the four‐point bending test. The optimal orientation and volume fracture of the micro constituents were identified using different models. The difference between the initial and optimized design was analyzed. The convergence of the provided optimization procedure was very rapid. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Numerical estimation of the thermal expansion of lamellar single domains in metal/ceramic composites
Authors: Stasiuk Galyna , Ziegler Tobias , Piat Romana , Neubrand Achim
Published: March 2011

A porous ceramic preform, the pore structure of which is created via a freeze‐casting technique, is infiltrated with a metal melt via sqeeze‐casting. The microstructure of the obtained metal/ceramic composites has lamellar domains with geometrical characteristics which are dependent on the manufacturing parameters. The aim of our study is to predict the coefficients of thermal expansion of single domains of parallel Al2O3 platelets embedded in Al. For this purpose, a homogenization procedure was employed for microstructure based finite element and micromechanical modeling. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Parallel Code for LES of Compressible Swirling Jet Flow Undergoing Vortex Breakdown
Authors: Luginsland T. , Bühler S. , Obrist D. , Kleiser L.
Published: March 2011

Swirling jets undergoing vortex breakdown occur in many technical applications, e.g. vortex burners, turbines and jet engines. To simulate the highly nonlinear dynamics of the flow, it is necessary to use high‐order numerical methods, leading to increased computational cost. To be able to perform simulations in acceptable turn‐around time, an available LES code for solving the filtered compressible Navier‐Stokes equations in cylindrical coordinates using compact finite‐difference schemes was parallelized for massively‐parallel architectures. The parallelization was done following the ghost‐cell approach for filtering in the three spatial directions. The inter‐process communication is handled using the message passing interface (MPI). The weak and strong scaling properties of the code indicate that it can be used for massively parallel simulations using several thousand processors. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamical Friction Phenomena and Friction‐Induced Vibrations in Pneumatic Sealings
Authors: Wangenheim Matthias
Published: March 2011

Especially from dry sliding contacts between solids the description of the friction by the law of Coulomb is well‐known. This law describes the relation between normal force and tangential force via the proportional factor μ, the coefficient of friction. This coefficient has to be derived empirically by experiments and is considered as being dependent only on the solid bodies' materials and surfaces. On the contrary seals are usually lubricated contacts. A viscoelastic seal material interacts with a hard solid counterpart in the state of mixed friction, i.e. viscous friction, hysteresis friction, and adhesion take effect simultaneously. The result is a friction characteristic which shows strong dependence on the sliding velocity, described e.g. by Richard Stribeck with the ‘Stribeck‐curve’, which was initially describing the friction of a journal bearing. One particularity of this curve is a decreasing coefficient of friction for increasing sliding velocity in the range of small velocities. It can be shown, that this decrease can cause friction induced vibrations and other undesired dynamical effects for certain mechanical properties of a system with sliding contact.

In this contribution the identification of friction induced dynamics and the development of a minimal model is carried out at the example of pneumatic sealing contacts in an industrial application. Furthermore model‐based measures are shown that prevent the application from performing undesired dynamical effects. The results are validated experimentally. (© 2010 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Genotoxic halofuranones in water: isomerization and acidity of mucohalic acids
Authors: Gómez‐Bombarelli Rafael , González‐Pérez Marina , Pérez‐Prior María Teresa , Calle Emilio , Casado Julio
Published: March 2011

Among the genotoxic halofuranones formed by chlorination in water are mucochloric acid (MCA, 3,4‐dichloro‐5‐hydroxyfuran‐2(5H)‐one) and mucobromic acid (MBA, 3,4‐dibromo‐5‐hydroxyfuran‐2(5H)‐one). These acids are direct genotoxins and potential carcinogens, with the capacity to alkylate the DNA bases. In recent years, they have also attracted attention in the synthesis of furanone derivatives. Mucohalic acids (MXA) exist in solution as an equilibrium between three species; a cyclic lactone‐lactol , an open‐chain aldehyde‐acid , and the dissociated form of the latter . The distribution of the three species in the equilibrium has synthetic, toxicological, and environmental implications owing to their different functionalization. The case of the neutral open‐chain form is of special interest, since it is expected to be highly reactive. We have experimentally determined the apparent dissociation constant of the cyclic species . Their values suggest that at neutral pH MXA are mostly present as the dissociated carboxylate‐aldehyde. The dissociation constant of the open‐chain neutral species and the cyclization equilibrium constant were determined in water and organic solvents, using density functional theory and ab initio methods. The results suggest that the undissociated aldehyde is a minor species at any given pH. The structure of MXA in solution and the influence of the level of theory on the calculated geometry are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Promoting effects of urethane derivatives of phenols on the ring‐opening polymerization of 1,3‐benzoxazines
Authors: Sudo Atsushi , Mori Atsushi , Endo Takeshi
Published: March 2011

For the purpose of reducing the induction period of the ring‐opening polymerization ofN‐methyl‐1,3‐benzoxazines, several urethanes were examined as promoters. The examined promoters3a–dwere the adducts of resorcinol and phenyl isocyanate, that of bisphenol A and phenyl isocyanate, that of resorcinol and butyl isocyanate, and that of 1,3‐propanediol and phenyl isocyanate, respectively. The aromatic urethanes3aand3b, which were adducts of the phenolic compounds and phenyl isocyanate, exhibited significant promoting effects. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Screening for distress and supportive care needs during the initial phase of the care process: a qualitative description of a clinical pilot experiment in a French cancer center
Authors: Dolbeault Sylvie , Boistard Béatrice , Meuric Jocelyne , Copel Laure , Brédart Anne
Published: March 2011

Objective: To provide a qualitative description of a clinical pilot experiment in a French cancer center, conducted by a nurse after the treatment decision consultation attended by new cancer patients during the initial phase of the care process.

Methods: The Psychological Distress Thermometer (PDS) and a problem checklist were administered to 255 patients before nurse consultation, helping her to manage the clinical interview, explore patient's distress and supportive care needs, and finally refer the patients in need to the required Supportive Care units.

Results: Patients were primarily referred to the social service unit (35% patients), followed by the physiotherapy unit (23.9%) and the psycho‐oncology unit (19.6% of patients). In cases of significant distress (43% patients with PDS>3), the percentage of patients referred to the psychosocial units increased (44% referred to the Social Unit, 35% to the Psycho‐Oncology Unit). However, the main interest of our screening procedure resides in its qualitative and didactic dimension, based on clinical training and cooperation with healthcare professionals during the process of investigating patients' distress and their supportive care needs. Difficulties and limitations are also described.

Conclusions: This first clinical experiment conducted among dedicated nurses involved in a Therapeutic Decision Consultation in a French cancer center has provided evidence in support of the idea that non‐specialist professionals are able to identify patients' distress and their Supportive Care needs (particularly in the psychosocial field) provided that they have received appropriate training. Copyright © 2011 John Wiley & Sons, Ltd.
Perceived positive impact of cancer among long‐term survivors of childhood cancer: a report from the childhood cancer survivor study
Authors: Zebrack Brad J. , Stuber Margaret L. , Meeske Kathleen A. , Phipps Sean , Krull Kevin R. , Liu Qi , Yasui Yutaka , Parry Carla , Hamilton Rachel , Robison Leslie L. , Zeltzer Lonnie K.
Published: March 2011

Objective

Investigations examining psychosocial adjustment among childhood cancer survivors have focused primarily on negative effects and psychopathology. Emergent literature suggests the existence of positive impact or adjustment experienced after cancer, as well. The purpose of this study is to examine the distribution of Perceived Positive Impact (PPI) and its correlates in young adult survivors of childhood cancer.

Methods

6425 survivors and 360 siblings completed a comprehensive health survey, inclusive of a modified version of the Post‐traumatic Growth Inventory (PTGI) as a measure of PPI. Linear regression models were used to examine demographic, disease and treatment characteristics associated with PPI.

Results

Survivors were significantly more likely than siblings to report PPI. Endorsement of PPI was significantly greater among female and non‐white survivors, and among survivors exposed to at least one intense therapy, a second malignancy or cancer recurrence. Survivors diagnosed at older ages and fewer years since diagnosis were more likely to report PPI. Income, education and marital/relationship status appeared to have varied relationships to PPI depending upon the subscale being evaluated.

Conclusions

The existence and variability of PPI in survivors in this study suggest that individual characteristics, inclusive of race, gender, cancer type, intensity of treatment, age at diagnosis and time since diagnosis, have unique and specific associations with different aspects of perceived positive outcomes of childhood cancer.

Copyright © 2011 John Wiley & Sons, Ltd.
Physical and Microbiological Characterisation of Staphylococcus epidermidis Inactivation by Dielectric Barrier Discharge Plasma
Authors: Helmke Andreas , Hoffmeister Dennis , Berge Frank , Emmert Steffen , Laspe Petra , Mertens Nina , Vioel Wolfgang , Weltmann Klaus‐Dieter
Published: March 2011

The inactivation of the Gram‐positive bacteria Staphylococcus epidermidis (ATCC 12228) in its vegetative state was studied in vitro after exposure to cold atmospheric pressure plasma generated by direct dielectric barrier discharge (DBD). Compared to UV radiation at 254 nm, plasma UV emission yielded no significant contribution to bacterial inactivation. Analysis of bacterial growth inhibition revealed a pH dependency on growth media. Yet, measurements combined with numerical simulations excluded the pH shift induced by plasma generated reactive species as the main cause of bacterial inactivation. Scanning electron microscopy (SEM) images showed no alteration of cell walls, while fluorescence microscopy revealed lethal damage to cell membranes even after 1 s treatment. When the cell membrane was already severely damaged, also degradation of the bacterial DNA by plasma treatment was found. We conclude that membrane damage due to reactive oxygen species (ROS) and DNA degradation are the main mechanisms of plasma‐induced bacterial death that is aggregated by milieu acidification.

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Insulin‐like growth factor‐2 (IGF2) loss of imprinting marks a field defect within human prostates containing cancer
Authors: Bhusari Sachin , Yang Bing , Kueck Jessica , Huang Wei , Jarrard David F.
Published: March 2011

BACKGROUND

Loss of imprinting (LOI) is an epigenetic alteration involving loss of parental origin‐specific expression at normally imprinted genes. A LOI for IGF2, a paracrine growth factor, has been implicated in the development of prostate and other cancers. In the current study, we define IGF2 LOI in histologically normal prostate tissues in relationship to tumor foci and gene expression.

METHODS

Microdissected tumor associated (TA) adjacent (2 mm) and distant (10 mm) tissues surrounding tumor foci were generated. IGF2 imprinting in informative prostate tissue sets was quantitated using a fluorescent primer extension assay and expression analyzed utilizing quantitative PCR. DNA methylation analyses were performed using quantitative pyrosequencing.

RESULTS

A marked IGF2 LOI was found in adjacent TA tissues (39 ± 3.1%) and did not significantly decrease in tissues distant (38 ± 5.3%) from tumor foci (45 ± 2.9%; P = 0.21). IGF2 imprinting correlated with IGF2 expression in TA tissues, but not within the tumor foci. Hypomethylation of the IGF2 DMR0 region correlated with decreased IGF2 expression in tumors (P < 0.01). The expression of IGF2 and its adjacent imprinted gene H19 were increased in adjacent and distant tissues compared to tumors (P < 0.05) indicating the importance of factors other than LOI in driving IGF2 expression.

CONCLUSIONS

LOI of IGF2 occurs not only adjacent to prostate tumor foci, but is widely prevalent even in distant areas within the peripheral zone. These data provide evidence for a widespread epigenetic field defect in histologically normal tissues that might be employed to identify prostate cancer in patients. Prostate 71:1621–1630, 2011. © 2011 Wiley‐Liss, Inc.
The effect of demographic and clinical factors on the relationship between BMI and PSA levels
Authors: Wright Jonathan L. , Lin Daniel W. , Stanford Janet L.
Published: March 2011

INTRODUCTION

Studies have reported lower prostate specific antigen (PSA) levels in men with a higher body mass index (BMI). Additional factors such as diabetes mellitus, benign prostatic hyperplasia (BPH) and certain medications may also affect PSA levels and confound the PSA–BMI association. In this study we evaluated the potential confounding effect of these factors on the obesity–PSA relationship and evaluated the association between these factors and PSA level.

METHODS

The study cohort consisted of 770 population‐based controls without a history of prostate cancer (PCa) who participated in a prior PCa study. Demographic, anthropometric, and medical history data were obtained, and PSA level was determined from blood drawn at the time of interview. Linear regression was performed to evaluate the PSA–BMI relationship, adjusting for potential confounders. Finally, a forward stepwise algorithm was used to determine which factors were independently associated with PSA values.

RESULTS

With increase in BMI (<25, 25–29, ≥30), the geometric mean PSA level declined (1.18, 1.13, and 0.94, respectively); obese men had a 17% (95% CI 0.70–0.99) lower age‐adjusted PSA level compared to normal weight men. However, this relationship was non‐significant (P = 0.17) in the multivariate model. Independent predictors of PSA level included age (β = 1.03, 95% CI 1.02–1.04), history of BPH (β = 1.48, 95% CI 1.27–1.72), current statin (β = 0.85, 95% CI 0.74–0.98), and NSAID use (β = 0.84, 95% CI 0.72–0.98).

CONCLUSION

The relationship between obesity and PSA is confounded by a number of factors, which likely explain the observed inverse association previously reported. These results should help in interpreting PSA values in men screened for PCa. Prostate 71:1631–1637, 2011. © 2011 Wiley‐Liss, Inc.
Low AZGP1 expression predicts for recurrence in margin‐positive, localized prostate cancer
Authors: Yip Po Yee , Kench James G. , Rasiah Krishan K. , Benito Ruth Pe , Lee C.‐Soon , Stricker Phillip D. , Henshall Susan M. , Sutherland Robert L. , Horvath Lisa G.
Published: March 2011

BACKGROUND

Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40–50% biochemical relapse rate at 5 years. Adjuvant radiotherapy improves biochemical progression‐free and overall survival in men with positive margins, but is associated with increased toxicity. There is an urgent need to identify new prognostic markers to define the group of patients who would benefit from multimodality therapy.

METHODS

Nuclear β‐catenin, membranous secreted frizzled‐related protein 4 (sFRP4), zinc‐alpha 2‐glycoprotein (AZGP1), and macrophage inhibitory cytokine‐1 (MIC‐1) have previously been identified as molecular markers of outcome in localized PC. From these published studies, we identified a subset of patients with positive margins. The aim of this study was to assess the association between these four molecular markers and outcome in men with margin‐positive, localized PC.

RESULTS

We identified 186 men with positive margins from 330 men with localized PC; 53% had preoperative PSA >10 ng/ml, 72% extraprostatic extension (EPE), 24% seminal vesicles involvement (SVI), and 57% RP Gleason score ≥ 7. AZGP1 (P = 0.009), membranous sFRP4 (P = 0.03) and MIC‐1 (P = 0.04) expression predicted for biochemical relapse on univariate analysis. Only absent/low AZGP1 expression (P = 0.01) was an independent predictor of recurrence in margin‐positive, localized PC when modeled with preoperative PSA (P = 0.2), EPE (P = 0.2), SVI (P = 0.4), Gleason score ≥ 7 (P = 0.5) and adjuvant treatment (P = 0.4). Furthermore, there was an association between absent/low AZGP1 expression and clinical recurrence (P = 0.007).

CONCLUSIONS

AZGP1 is a potential molecular marker for biochemical relapse in men with margin‐positive, localized PC. Routine assessment of this biomarker may lead to better selection of patients who will benefit from post‐RP radiotherapy. Prostate 71:1638–1645, 2011. © 2011 Wiley‐Liss, Inc.
The calcium sensor STIM1 is regulated by androgens in prostate stromal cells
Authors: Berry Paul A. , Birnie Richard , Droop Alastair P. , Maitland Norman J. , Collins Anne T.
Published: March 2011

BACKGROUND

Prostate development and maintenance in the adult results from an interaction of stromal and glandular components. Androgens can drive this process by direct action on the stroma. We investigated whether there was a direct link between androgens and another key regulator of stromal cells, intracellular Ca2+ ([Ca2+]i).

METHODS

Prostate stromal cells were freshly obtained and cultures derived from patients with benign prostatic hyperplasia. Gene expression in dihydrotestosterone treated and untreated cells was compared using Affymetrix gene expression arrays and Ca2+ regulated features were identified by Gene Ontology (GO). Changes in [Ca2+]i were determined in Fluo‐4 loaded cells. Androgen regulation was confirmed by chromatin immunoprecipitaion.

RESULTS

Stromal cell cultures were sorted for expression of integrin α1β1, which enriched for cells expressing the androgen receptor (AR). We identified key functional categories, within the androgen‐induced gene expression signature, focusing on genes involved in calcium signaling. From this analysis, stromal interaction molecule‐1 (STIM1) was identified as a significantly differentially expressed gene with four relevant associated GO terms. DNA sequence analysis showed that the promoter region of STIM1 contained putative androgen response element sequences in which AR binding ability of STIM1 was confirmed. Androgens directly regulated STIM1 expression and STIM1 effects on store‐operated calcium entry were inhibited by STIM1 knock‐down. Reduced STIM1 expression in prostate stromal cells led to a reduction in basal Ca2+ levels, the amount of Ca2+ released by thapsigargin and a reduction in store filling following TG‐induced store depletion.

CONCLUSIONS

These results indicate that androgens modulate [Ca2+]i through the direct regulation of the STIM1 gene by AR binding to the STIM1 promoter. Prostate 71:1646–1655, 2011. © 2011 Wiley‐Liss, Inc.
Analysis of water patterns in protein kinase binding sites
Authors: Barillari Caterina , Duncan Anna L. , Westwood Isaac M. , Blagg Julian , van Montfort Rob L. M.
Published: March 2011

Deregulation of protein kinases is associated with numerous diseases, making them important targets for drug discovery. The majority of drugs target the catalytic site of these proteins, but due to the high level of similarity within the ATP binding sites of protein kinases, it is often difficult to achieve the required pharmacological selectivity. In this study, we describe the identification and subsequent analysis of water patterns in the ATP binding sites of 171 protein kinase structures, comprising 19 different kinases from various branches of the kinome, and demonstrate that structurally similar binding sites often have significantly different water patterns. We show that the observed variations in water patterns of different, but structurally similar kinases can be exploited in the structure‐based design of potent and selective kinase inhibitors. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Structural memory of natively unfolded tau protein detected by small‐angle X‐ray scattering
Authors: Shkumatov Alexander V. , Chinnathambi Subashchandrabose , Mandelkow Eckhard , Svergun Dmitri I.
Published: March 2011

Small‐angle X‐ray scattering (SAXS) is a universal low‐resolution method to study size and shape of globular proteins in solution but recent developments facilitate the quantitative characterization of the structure and structural transitions of metastable systems like partially or completely unfolded proteins. We present here a study of temperature induced transitions in tau, a natively unfolded protein involved in Alzheimer's disease. Previous studies on full length tau and several disease‐related mutants provided information about the residual structure in different domains revealing a specific role and extended conformations of the so‐called repeat domains, which are considered to be responsible for the formation of amyloid‐like fibrils (“paired helical filaments”). Here, we employ SAXS to investigate the temperature dependent properties of tau. Slow heating/cooling of the full length protein from 10°C to 50°C did not lead to detectable changes in the overall size. Surprisingly, quick heating/cooling caused tau to adopt a significantly more compact conformation, which was stable over up to 3 h and represents a structural “memory” effect. This compaction is not observed for the shorter tau constructs containing largely the repeat domains. The structural and functional implications of the observed unusual behavior of tau under nonequilibrium conditions are discussed. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Computer simulation study of amyloid fibril formation by palindromic sequences in prion peptides
Authors: Wagoner Victoria A. , Cheon Mookyung , Chang Iksoo , Hall Carol K.
Published: March 2011

We simulate the aggregation of large systems containing palindromic peptides from the Syrian hamster prion protein SHaPrP 113–120 (AGAAAAGA) and the mouse prion protein MoPrP 111–120 (VAGAAAAGAV) and eight sequence variations: GAAAAAAG, (AG)4, A8, GAAAGAAA, A10, V10, GAVAAAAVAG, and VAVAAAAVAV The first two peptides are thought to act as the Velcro that holds the parent prion proteins together in amyloid structures and can form fibrils themselves. Kinetic events along the fibrillization pathway influence the types of structures that occur and variations in the sequence affect aggregation kinetics and fibrillar structure. Discontinuous molecular dynamics simulations using the PRIME20 force field are performed on systems containing 48 peptides starting from a random coil configuration. Depending on the sequence, fibrillar structures form spontaneously over a range of temperatures, below which amorphous aggregates form and above which no aggregation occurs. AGAAAAGA forms well organized fibrillar structures whereas VAGAAAAGAV forms less well organized structures that are partially fibrillar and partially amorphous. The degree of order in the fibrillar structure stems in part from the types of kinetic events leading up to its formation, with AGAAAAGA forming less amorphous structures early in the simulation than VAGAAAAGAV. The ability to form fibrils increases as the chain length and the length of the stretch of hydrophobic residues increase. However as the hydrophobicity of the sequence increases, the ability to form well‐ordered structures decreases. Thus, longer hydrophobic sequences form slightly disordered aggregates that are partially fibrillar and partially amorphous. Subtle changes in sequence result in slightly different fibril structures. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Crystal structure of a metal‐dependent phosphoesterase (YP_910028.1) from Bifidobacterium adolescentis: Computational prediction and experimental validation of phosphoesterase activity
Authors: Han Gye Won , Ko Jaeju , Farr Carol L. , Deller Marc C. , Xu Qingping , Chiu Hsiu‐Ju , Miller Mitchell D. , Sefcikova Jana , Somarowthu Srinivas , Beuning Penny J. , Elsliger Marc‐André , Deacon Ashley M. , Godzik Adam , Lesley Scott A. , Wilson Ian A. , Ondrechen Mary Jo
Published: March 2011

The crystal structures of an unliganded and adenosine 5′‐monophosphate (AMP) bound, metal‐dependent phosphoesterase (YP_910028.1) from Bifidobacterium adolescentis are reported at 2.4 and 1.94 Å, respectively. Functional characterization of this enzyme was guided by computational analysis and then confirmed by experiment. The structure consists of a polymerase and histidinol phosphatase (PHP, Pfam: PF02811) domain with a second domain (residues 105‐178) inserted in the middle of the PHP sequence. The insert domain functions in binding AMP, but the precise function and substrate specificity of this domain are unknown. Initial bioinformatics analyses yielded multiple potential functional leads, with most of them suggesting DNA polymerase or DNA replication activity. Phylogenetic analysis indicated a potential DNA polymerase function that was somewhat supported by global structural comparisons identifying the closest structural match to the alpha subunit of DNA polymerase III. However, several other functional predictions, including phosphoesterase, could not be excluded. Theoretical microscopic anomalous titration curve shapes, a computational method for the prediction of active sites from protein 3D structures, identified potential reactive residues in YP_910028.1. Further analysis of the predicted active site and local comparison with its closest structure matches strongly suggested phosphoesterase activity, which was confirmed experimentally. Primer extension assays on both normal and mismatched DNA show neither extension nor degradation and provide evidence that YP_910028.1 has neither DNA polymerase activity nor DNA‐proofreading activity. These results suggest that many of the sequence neighbors previously annotated as having DNA polymerase activity may actually be misannotated. Proteins 2011. © 2011 Wiley‐Liss, Inc.
Early days of protein hydrogen exchange: 1954–1972
Authors: Baldwin Robert L.
Published: March 2011

Hydrogen exchange (HX) is recognized today as one of the most powerful and versatile tools available to protein scientists, especially for studying protein conformational change. This short history traces the beginnings of the HX method and the basic problems that faced the founders. Protein HX began as a simple idea with a straightforward goal, but the first experiments revealed both the unexpected complexity of the subject and the potential power of the method for probing deep into how proteins work. By 1972, the chemistry of the exchange reaction in peptides began to be well understood, but the challenge of getting and interpreting data on HX for individual peptide NH protons in proteins remained for decades longer. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Structural characterization of the mitomycin 7‐O‐methyltransferase
Authors: Singh Shanteri , Chang Aram , Goff Randal D. , Bingman Craig A. , Grüschow Sabine , Sherman David H. , Phillips George N. , Thorson Jon S.
Published: March 2011

Mitomycins are quinone‐containing antibiotics, widely used as antitumor drugs in chemotherapy. Mitomycin‐7‐O‐methyltransferase (MmcR), a key tailoring enzyme involved in the biosynthesis of mitomycin in Streptomyces lavendulae, catalyzes the 7‐O‐methylation of both C9β‐ and C9α‐configured 7‐hydroxymitomycins. We have determined the crystal structures of the MmcR–S‐adenosylhomocysteine (SAH) binary complex and MmcR–SAH–mitomycin A (MMA) ternary complex at resolutions of 1.9and 2.3 Å, respectively. The study revealed MmcR to adopt a common S‐adenosyl‐L‐methionine‐dependent O‐methyltransferase fold and the presence of a structurally conserved active site general acid–base pair is consistent with a proton‐assisted methyltransfer common to most methyltransferases. Given the importance of C7 alkylation to modulate mitomycin redox potential, this study may also present a template toward the future engineering of catalysts to generate uniquely bioactive mitomycins. Proteins 2011. © 2011 Wiley‐Liss, Inc.
Toward the quantum chemical calculation of nuclear magnetic resonance chemical shifts of proteins
Authors: Frank Andrea , Onila Ionut , Möller Heiko M. , Exner Thomas E.
Published: March 2011

Despite the many protein structures solved successfully by nuclear magnetic resonance (NMR) spectroscopy, quality control of NMR structures is still by far not as well established and standardized as in crystallography. Therefore, there is still the need for new, independent, and unbiased evaluation tools to identify problematic parts and in the best case also to give guidelines that how to fix them. We present here, quantum chemical calculations of NMR chemical shifts for many proteins based on our fragment‐based quantum chemical method: the adjustable density matrix assembler (ADMA). These results show that 13C chemical shifts of reasonable accuracy can be obtained that can already provide a powerful measure for the structure validation. 1H and even more 15N chemical shifts deviate more strongly from experiment due to the insufficient treatment of solvent effects and conformational averaging. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Cell selectivity and interaction with model membranes of Val/Arg‐rich peptides
Authors: Ma Qing‐Quan , Shan An‐Shan , Dong Na , Gu Yao , Sun Wen‐Yu , Hu Wan‐Ning , Feng Xing‐Jun
Published: March 2011

Antimicrobial peptides are major components of the innate self‐defence system and a large number of peptides have been designed to study the mechanism of action. In the present study, a small combinatorial library was designed to study whether the biological activity of Val/Arg‐rich peptides is associated with targeted cell membranes. The peptides were produced by segregating hydrophilic residues on the polar side and hydrophobic residues on the opposite side. The peptides displayed strong antimicrobial activity against Gram‐negative and Gram‐positive bacteria, but weak haemolysis even at a concentration of 256 µM. CD spectra showed that the peptides formed α‐helical‐rich structure in the presence of negatively charged membranes. The tryptophan fluorescence and quenching experiments indicated that the peptides bound preferentially to negatively charged phospholipids over zwitterionic phospholipids, which corresponds well with the biological activity data. In the in vivo experiment, the peptide G6 decreased the bacterial counts in the mouse peritoneum and increased survival after 7 days. Overall, a high binding affinity with negatively charged phospholipids correlated closely with the cell selectivity of the peptides and some peptides in this study may be likely candidates for the development of antibacterial agents. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
Signal readout for pyroelectric detector based on relaxor ferroelectric single crystals
Authors: Wang Jiang , Jing Yiou , Jing Weiping , Li Yan Jin
Published: March 2011

Relaxor‐based ferroelectric single crystals, such as (1 − x)Pb(Mg1/3Nb2/3)O3xPbTiO3 (PMNxPT, or PMNT) single crystals, exhibit large pyroelectric response, low thermal diffusivity, and high temperature stability. To fabricate high performance infrared detectors with relaxor‐based single crystals, the related readout circuit was investigated to increase signal‐to‐noise ratio, and 8 × 1 CMOS readout circuit is fabricated to gain very weak current, which provides a solution for uncooled large focal plane arrays devices based on relaxor‐based single crystals.
A compact quantum statistical model for the ballistic nanoscale MOSFETs
Authors: Varpula A. , Lebedeva N. , Kuivalainen P.
Published: March 2011

We develop an analytical quantum statistical model for nanoscale metal‐oxide‐semiconductor field‐effect transistors (MOSFETs). The model describes transport both in the scattering‐limited and ballistic regimes. The expression for the channel current is derived with the Keldysh nonequilibrium Green's function technique. The obtained quantum statistical current expression reduces to the semiclassical one in the absence of scattering. The model indicates that in nanoscale devices the scattering processes become dependent on the bias voltages. The calculated results for the I–V characteristics are in good agreement with the experimental results in the case of a 70 nm MOSFET. The model includes a minimal number of fitting parameters and it can be used in the design of ultra large‐scale integrated circuits.
Raman studies of hexagonal MoO3 at high pressure
Authors: Zhang C. C. , Zheng L. , Zhang Z. M. , Dai R. C. , Wang Z. P. , Zhang J. W. , Ding Z. J.
Published: March 2011

The transition‐metal oxide MoO3 is an important semiconductor and has various technological applications in catalysts, electrochromic and photochromic devices, gas sensors, and battery electrodes. In this study, the hexagonal MoO3 prepared by a hydrothermal method is in morphology of microrod with diameter of 0.8–1.2 µm and length of 2.0–4.3 µm. Its structural stability was investigated by an in situ Raman scattering method in a diamond anvil cell up to 28.7 GPa at room temperature. The new Raman peak around 1000 cm−1 implies that a phase transition from hexagonal to amorphous starts at 5.6 GPa, and the evolution of the Raman spectra indicates that the structural transition is completed at about 13.2 GPa. After releasing pressure to ambient condition, the Raman spectrum pattern of the high pressure phase was retained, revealing that the phase transition is irreversible.
Maternal meddling in neonatal sharks: implications for interpreting stable isotopes in young animals
Authors: Olin Jill A. , Hussey Nigel E. , Fritts Mark , Heupel Michelle R. , Simpfendorfer Colin A. , Poulakis Gregg R. , Fisk Aaron T.
Published: March 2011

Stable isotopes of neonatal vertebrates reflect those of their mother's diet and foraging location. Evaluating feeding strategies and habitat use of neonates is consequently complicated by the maternal isotopic signal and its subsequent elimination with growth. Thus, methods that measure the loss of the maternal signal, i.e. when the isotopic signal of a neonate reflects its own diet, are needed. Values of δ13C and δ15N were measured in liver and muscle tissues of <1 year old bull (Carcharhinus leucas) and Atlantic sharpnose (Rhizoprionodon terraenovae) sharks and related to age using, total length, date sampled and umbilical scar stage (USS). We observed a decline in δ13C and δ15N values with age that was different among species, similar among isotopes, and greater in liver than in muscle; highlighting that retention of the maternal signal is dependent on species‐specific life history and tissue characteristics. USS was most effective for assessing the loss of the maternal isotopic signal in the faster growing Atlantic sharpnose shark, but was less effective for the slower growing bull shark. Total length and date sampled were overall less effective and may be more informative for slower growing species when coupled with USS, as variable size at birth and misclassification of animals >1 year old, which remain in nursery habitats, increase the variability of the isotopic values. Consideration of the maternal signal and measuring its loss are thus necessary when analyzing the stable isotopes of young animals, as there is potential to misinterpret feeding strategies, over‐estimate trophic position and incorrectly assign carbon source. Copyright © 2011 John Wiley & Sons, Ltd.
Interfacial reactions of nickel ion containing multilayers and nickel ultra‐thin films with an interpenetrating polymer network substrate
Authors: Tang Dongyan , Han Shuai , Li Ji
Published: March 2011

An interpenetrating polymer network (IPN) substrate was prepared by dip‐pulling a silicon wafer or glass plate into polymer precursors, followed by solidification at room temperature. The nickel ion containing Langmuir–Blodgett (LB) multilayers was subsequently fabricated onto the IPN substrate by a LB technique, and then the nickel ultra‐thin films were deposited by chemical reduction. The interfacial reactions, the metal transformations and the non‐metal bond types during the film formation were detected by the X‐ray photoelectron spectroscopy, atomic force microscope and attenuated total reflection infrared spectroscopy. Copyright © 2011 John Wiley & Sons, Ltd.
Flexible modeling of the effects of continuous prognostic factors in relative survival
Authors: Mahboubi Amel , Abrahamowicz Michal , Giorgi Roch , Binquet Christine , Bonithon‐Kopp Claire , Quantin Catherine
Published: March 2011

Relative survival methods permit separating the effects of prognostic factors on disease‐related ‘excess mortality’ from their effects on other‐causes ‘natural mortality’, even when individual causes of death are unknown. As in conventional ‘crude’ survival, accurate assessment of prognostic factors requires testing and possibly modeling of non‐proportional effects and, for continuous covariates, of non‐linear relationships with the hazard. We propose a flexible extension of the additive‐hazards relative survival model, in which the observed all‐causes mortality hazard is represented by a sum of disease‐related ‘excess’ and natural mortality hazards. In our flexible model, the three functions representing (i) the baseline hazard for ‘excess’ mortality, (ii) the time‐dependent effects, and (iii) for continuous covariates, non‐linear effects, on the logarithm of this hazard, are all modeled by low‐dimension cubic regression splines. Non‐parametric likelihood ratio tests are proposed to test the time‐dependent and non‐linear effects. The accuracy of the estimated functions is evaluated in multivariable simulations. To illustrate the new insights offered by the proposed model, we apply it to re‐assess the effects of patient age and of secular trends on disease‐related mortality in colon cancer. Copyright © 2011 John Wiley & Sons, Ltd.