bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor
Authors: Pace Thaddeus W. W. , Spencer Robert L.
Published: January 2005

Glucocorticoid negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng·10 μl−1·2 h−1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.
Acute selective glycogen synthase kinase-3 inhibition enhances insulin signaling in prediabetic insulin-resistant rat skeletal muscle
Authors: Dokken Betsy B. , Sloniger Julie A. , Henriksen Erik J.
Published: January 2005

Glycogen synthase kinase-3 (GSK3) has been implicated in the multifactorial etiology of skeletal muscle insulin resistance in animal models and in human type 2 diabetic subjects. However, the potential molecular mechanisms involved are not yet fully understood. Therefore, we determined if selective GSK3 inhibition in vitro leads to an improvement in insulin action on glucose transport activity in isolated skeletal muscle of insulin-resistant, prediabetic obese Zucker rats and if these effects of GSK3 inhibition are associated with enhanced insulin signaling. Type I soleus and type IIb epitrochlearis muscles from female obese Zucker rats were incubated in the absence or presence of a selective, small organic GSK3 inhibitor (1 μM CT118637, Ki< 10 nM for GSK3α and GSK3β). Maximal insulin stimulation (5 mU/ml) of glucose transport activity, glycogen synthase activity, and selected insulin-signaling factors [tyrosine phosphorylation of insulin receptor (IR) and IRS-1, IRS-1 associated with p85 subunit of phosphatidylinositol 3-kinase, and serine phosphorylation of Akt and GSK3] were assessed. GSK3 inhibition enhanced ( P <0.05) basal glycogen synthase activity and insulin-stimulated glucose transport in obese epitrochlearis (81 and 24%) and soleus (108 and 20%) muscles. GSK3 inhibition did not modify insulin-stimulated tyrosine phosphorylation of IR β-subunit in either muscle type. However, in obese soleus, GSK3 inhibition enhanced (all P < 0.05) insulin-stimulated IRS-1 tyrosine phosphorylation (45%), IRS-1-associated p85 (72%), Akt1/2 serine phosphorylation (30%), and GSK3β serine phosphorylation (39%). Substantially smaller GSK3 inhibitor-mediated enhancements of insulin action on these insulin signaling factors were observed in obese epitrochlearis. These results indicate that selective GSK3 inhibition enhances insulin action in insulin-resistant skeletal muscle of the prediabetic obese Zucker rat, at least in part by relieving the deleterious effects of GSK3 action on post-IR insulin signaling. These effects of GSK3 inhibition on insulin action are greater in type I muscle than in type IIb muscle from these insulin-resistant animals.
Using2H2O to study the influence of feeding on protein synthesis: effect of isotope equilibration in vivo vs. in cell culture
Authors: Dufner Danielle A. , Bederman Ilya R. , Brunengraber Daniel Z. , Rachdaoui Nadia , Ismail-Beigi Faramarz , Siegfried Brett A. , Kimball Scot R. , Previs Stephen F.
Published: January 2005

We previously reported that2H2O can be used to measure rates of protein synthesis during prolonged steady-state conditions (Previs SF, Fatica R, Chandramouli V, Alexander JC, Brunengraber H, and Landau BR. Am J Physiol Endocrinol Metab 286: E665-E672, 2004). The underlying premise of our method is that following the administration of2H2O,2H atoms in body water rapidly equilibrate with free alanine before it is incorporated into newly synthesized proteins. We have now directly examined whether2H2O can be used to measure the influence of a single meal on protein synthesis. In addition, we have compared the use of2H2O for measuring rates of protein synthesis in vivo vs. in cell culture. Using a rat model, we observed rapid equilibration between2H in body water and free alanine; therefore we were able to study the response of protein synthesis to a single meal. We observed that ∼50% of the plasma albumin that is synthesized over the course of 24 h is made within ∼5 h after eating (in rats trained to eat a complete 24-h ration of food in a single meal). Contrary to what we observed in vivo, feeding (the replenishment of cell culture medium) does influence the use of2H2O for in vitro studies. In particular, since there can be slow equilibration of2H between water and alanine in the cell culture medium, special consideration must be made to avoid underestimating the rate of protein synthesis in vitro.
Teaching Internet skills to pupils with a severe visual impairment
Authors: Jones Rob
Published: January 2005

In Scotland, national guidelines were laid down for the content of, and the targets to be attained in, Information and Communication Technology, for all 5-14-year-old pupils. This article gives an account of the planning, design, implementation and evaluation within a specialist school for blind and partially-sighted pupils of a teaching programme to enable them to access and use the web as part of this curriculum. An analysis was made of the specific core skills required by visually impaired students for the Searching and Researching Strand of the Guidelines. The problems encountered by the teacher-designer and pupils with different degrees of residual vision are described, and an assessment is offered of the impact and success of the teaching programme. The importance is stressed of web-site designers to be sensitive to the needs of visually-impaired users when preparing their information sites.
Learning to read by touch: developing braille reading schemes
Authors: Arnold Alison
Published: January 2005

This article describes the work of a group of professionals in the United Kingdom known as the VIEW Braille Literacy Committee, committed to the development of teaching braille. Members meet each school term and have had the support of the Royal National Institute of the Blind (RNIB) in realizing numerous projects aimed at improving access to literacy for all those learning to read through touch. A description is given of some of the reading schemes designed by members of the group, of their underlying rationale, of the importance of pre-braille reading skills, of issues to do with motivation, and of the order of introducing braille short-forms and contractions.
Network 1000: the changing needs and circumstances of visually-impaired people: project overview
Authors: Corcoran C. , Douglas G. , Pavey S. , Fielding A. , McLinden M. , McCall S.
Published: January 2005

This article outlines the progress of a newly-commissioned three year study known as Network 1000. It is a three-year project funded through the Community Fund and is being carried out by the University of Birmingham on behalf of Vision 2020. The project’s aim is to create a panel survey of 1000 visually-impaired people to be interviewed regularly over the three-year period, and hopefully beyond, enabling their changing needs and circumstances to be monitored over time. The findings will be used to influence policy-makers and service-providers, and will also be disseminated to a wider audience of people with an interest in visual impairment. Building on the longitudinal nature of the project enables the project team to develop a methodology that is both democratic and inclusive. The underlying research philosophy is one of inclusion and participation and in this respect the people this research affects the most - those who are visually impaired - are involved in all stages of the research process. People with a visual impairment have played a key role in generating the data and the themes that will drive the construction of the main survey instrument. The article is divided into five sections that describe the progress of the project to date: first, it briefly outlines the background to the project; second, it describes the underlying philosophy behind the democratic approach to inclusion and participant involvement; third, it presents preliminary results from generative interviews; fourth, it discusses how the team will recruit participants to the project with particular reference to the two-stage sample design that has been adopted; and finally, it describes how this two-stage approach will be operationalized. The article concludes by outlining the next phase of the project and with a short reflection on the research process to date.
A trend analysis of the low-vision literature
Authors: Goodrich Gregory L. , Arditi Aries
Published: January 2005

An account is given of the design and compilation of a freely-available database, updated on a monthly schedule, listing journals, books, conference proceedings and online publications concerned with any and every aspect of low vision. Specific topic areas can be located by means of keywords and through other bibliographical details such as the author’s name, year of publication, etc. The authors present a summary historical analysis revealing that there has been an unprecedented rise over the last few decades in the number and diversity of journals and other literature sources addressing issues to do with low vision. Among the opportunities provided by the database are searches to ascertain not only what is currently being practiced and researched but also to identify the changes in the priorities being given to the multitude of topics of interest to optometrists, ophthalmologists, paediatricians, psychologists, educators, rehabilitation practitioners, epidemiologists, gerontologists and other professional workers.
Fuzzy Modal Active Control of Flexible Structures
Authors: Malhis M. , Gaudiller L. , Der Hagopian J.
Published: January 2005

In this paper we propose a new active control strategy to control the dynamic behavior of flexible structures: fuzzy modal control (FMC). This strategy, based on the modal state feedback of the structure, uses independent fuzzy controllers for each mode to be controlled. This method is applied to a flexible beam controlled by a transverse plane of action using piezoelectric actuators. First of all, a model of a piezoelectric actuator is proposed, followed by the formulation of a finite-element model of the mechanical structure/actuator. The model is then fitted using an identification of the characteristics. After modal reduction, the FMC is carried out in two steps: the control of the beam in only one transverse direction by a piezoelectric pusher, then in two transverse directions by two orthogonal piezoelectric pushers located on the same plane. A digital controller was built in the Matlab®-Simulink® environment, and implemented on specialized cards in order to perform the corresponding experiment. The method is validated by comparing the results between the simulation and the experiment.
On Saturation Control of a Non-Ideal Vibrating Portal Frame Foundation Type Shear-Building
Authors: Felix Jorge L. Palacios , Balthazar José M. , Brasil Reyolando M. L. R. F.
Published: January 2005

In this paper, we examine the nonlinear control method based on the saturation phenomenon and of systems coupled with quadratic nonlinear ties applied to a shear-building portal plane frame foundation that supports an unbalanced direct current with limited power supply (non-ideal system). We analyze the equations of motion by using the method of averaging and numerical simulation. The interaction of the non-ideal structure with the saturation controller may lead to the occurrence of interesting phenomena during the forward passage through the several resonance states of the systems. Special attention is focused on passage through resonance when the non-ideal excitation frequency is near the portal frame natural frequency and when the non-ideal system frequency is approximately twice the controller frequency (two-to-one internal resonance).
Design of Frequency-Dependent Weighting Functions for H2 Control of Seismic-Excited Structures
Authors: Min Kyung-Won , Chung Lan , Joo Seok-Jun , Kim Jinkoo
Published: January 2005

In this paper we investigate a systematic procedure for determining frequency-dependent weighting functions for an H2 controller in the frequency domain. Based on experimental results from the system identification of a model structure with an active mass driver, we choose frequency-dependent weighting functions, including filters on an earthquake input model, sensor noise, control output, and control force. These are incorporated into the plant to produce an optimal controller. Combining the weighting functions and filters and comparing the trade-off problem between response reduction and control force, an optimal combination of weighting functions and filters is determined. The performance of the designed H2 controller is evaluated by shaking-table tests of a three-story scaled model with an active mass driver.
Optimization Analysis of Impact Viscous Damper for Controlling Self-Excited Vibrations
Authors: Asfar K. R. , Akour S. N.
Published: January 2005

We present a numerical study for the suppression of self-excited vibrations represented by a Rayleigh oscillator using an impact viscous damper. A systematic approach based on a univariate search optimization method is used to determine the best design parameters for suppressing self-excited vibrations. The suggested system is found to be effective in suppressing this type of vibration. Optimum parameters for complete quenching of such vibrations are obtained. We investigate quasi-static as well as dynamic variations of the bifurcation parameter for both supercritical and subcritical Hopf bifurcation.
The actin cytoskeleton differentially regulates platelet α-granule and dense-granule secretion
Authors: Flaumenhaft Robert , Dilks James R. , Rozenvayn Nataliya , Monahan-Earley Rita A. , Feng Dian , Dvorak Ann M.
Published: January 2005

Stimulation of platelets with strong agonists results in centralization of cytoplasmic organelles and secretion of granules. These observations have led to the supposition that cytoskeletal contraction facilitates granule release by promoting the interaction of granules with one another and with membranes of the open canalicular system. Yet, the influence of the actin cytoskeleton in controlling the membrane fusion events that mediate granule secretion remains largely unknown. To evaluate the role of the actin cytoskeleton in platelet granule secretion, we have assessed the effects of latrunculin A and cytochalasin E on granule secretion. Exposure of platelets to low concentrations of these reagents resulted in acceleration and augmentation of agonist-induced α-granule secretion with comparatively modest effects on dense granule secretion. In contrast, exposure of platelets to high concentrations of latrunculin A inhibited agonist-induced α-granule secretion but stimulated dense granule secretion. Incubation of permeabilized platelets with low concentrations of latrunculin A primed platelets for Ca2+- or guanosine triphosphate (GTP)-γ-S-induced α-granule secretion. Latrunculin A-dependent α-granule secretion was inhibited by antibodies directed at vesicle-associated membrane protein (VAMP), demonstrating that latrunculin A supports soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein-dependent membrane fusion. These results indicate that the actin cytoskeleton interferes with platelet exocytosis and differentially regulates α-granule and dense granule secretion.
Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia
Authors: Rondelli Damiano , Barosi Giovanni , Bacigalupo Andrea , Prchal Josef T. , Popat Uday , Alessandrino Emilio P. , Spivak Jerry L. , Smith B. Douglas , Klingemann Hans G. , Fruchtman Steven , Hoffman Ronald
Published: January 2005

A total of 21 patients with myelofibrosis with myeloid metaplasia (MMM), with a median age of 54 years (range, 27-68 years), were prepared with a reduced-intensity conditioning (RIC) regimen. The patients received an allogeneic marrow (n = 3) or peripheral blood stem-cell (n = 18) transplant from HLA-matched related (n = 18) or unrelated (n = 2), or 1 Ag-mismatched related (n = 1), donors. RIC regimens included fludarabine/total body irradiation 200 cGy (n = 5) or 450 cGy (n = 1), fludarabine/melphalan (n = 7), thiotepa/cyclophosphamide (n = 7), and thiotepa/fludarabine (n = 1). At the time of transplantation, all of the patients were at intermediate (n = 13) or high (n = 8) risk, according to the Dupriez classification. Of the patients, 19 had grade III or IV marrow fibrosis. All of the patients achieved full engraftment but one. Posttransplantation chimerism analysis showed more than 95% donor cells in 18 patients, while 2 patients achieved complete donor chimerism after donor leukocyte infusion (DLI). Acute graft-versus-host disease (GVHD) grades II to IV was observed in 7 patients, grades III to IV in 2, and extensive chronic GVHD in 8 of 18 evaluable patients. There were 3 patients who died from acute GVHD, infection, and relapse. There are 18 patients alive 12 to 122 months (median, 31 months) after transplantation, and 17 are in remission (1 after a second transplantation). The use of RIC regimens in allogeneic stem cell transplantation results in prolonged survival in intermediate/high-risk MMM patients.
Hepcidin in iron overload disorders
Authors: Papanikolaou George , Tzilianos Michalis , Christakis John I. , Bogdanos Dionisios , Tsimirika Konstantina , MacFarlane Julie , Goldberg Y. Paul , Sakellaropoulos Nikos , Ganz Tomas , Nemeth Elizabeta
Published: January 2005

Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. We measured urinary hepcidin in patients with other genetic causes of iron overload. Hepcidin was found to be suppressed in patients with thalassemia syndromes and congenital dyserythropoietic anemia type 1 and was undetectable in patients with juvenile hemochromatosis with HAMP mutations. Of interest, urine hepcidin levels were significantly elevated in 2 patients with hemochromatosis type 4. These findings extend the spectrum of iron disorders with hepcidin deficiency and underscore the critical importance of the hepcidin–ferroportin interaction in iron homeostasis.
Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammation
Authors: Nabbe Karin CAM , van Lent Peter LEM , Holthuysen Astrid EM , Sloëtjes Annet W , Koch Alisa E , Radstake Timothy RDJ , van den Berg Wim B
Published: January 2005

During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcγ receptors (FcγRs) (mainly FcγRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) cytokine abundantly found in synovial fluid of patients with rheumatoid arthritis, has been shown to reduce joint inflammation and bone destruction during experimental arthritis. However, the effect on severe cartilage destruction has not been studied in detail. We have now investigated the role of IL-13 in chondrocyte death and MMP-mediated cartilage damage during ICA. IL-13 was locally overexpressed in knee joints after injection of an adenovirus encoding IL-13 (AxCAhIL-13), 1 day before the onset of arthritis; injection of AxCANI (an empty adenoviral construct) was used as a control. IL-13 significantly increased the amount of inflammatory cells in the synovial lining and the joint cavity, by 30% to 60% at day 3 after the onset of ICA. Despite the enhanced inflammatory response, chondrocyte death was diminished by two-thirds at days 3 and 7. The mRNA level of FcγRI, a receptor shown to be crucial in the induction of chondrocyte death, was significantly down-regulated in synovium. Furthermore, MMP-mediated cartilage damage, measured as neoepitope (VDIPEN) expression using immunolocalization, was halved. In contrast, mRNA levels of MMP-3, -9, -12, and -13 were significantly higher and IL-1 protein, which induces production of latent MMPs, was increased fivefold by IL-13. This study demonstrates that IL-13 overexpression during ICA diminished both chondrocyte death and MMP-mediated VDIPEN expression, even though joint inflammation was enhanced.
Coronary artery bypass surgery and longitudinal evaluation of the autonomic cardiovascular function
Authors: Soares Pedro PauloS , Moreno Adalgiza M , Cravo Sérgio LD , Nóbrega Antonio ClaudioL
Published: January 2005

Introduction

Imbalance in autonomic cardiovascular function increases the risk for sudden death in patients with coronary artery disease (CAD), but the time course of the impact of coronary artery bypass grafting (CABG) on autonomic function has been little studied. Thus, the purpose of the present study was to determine the effects of the CABG on the cardiovascular autonomic function.

Methods

Patients undergoing CABG (n = 13) and two matched control groups (patients with CAD who refused surgical treatment [n = 9], and healthy volunteers [n = 9]) underwent a prospective longitudinal study consisting of autonomic evaluation before and after (3, 6, 15, 30, 60, and 90 days) surgery, including measurement of heart rate variability (HRV), respiratory sinus arrhythmia (RSA), and Valsalva maneuver.

Results

After CABG there was a decrease in, and a later recovery of, (1) the HRV in the time domain and in the frequency domain, (2) RSA, and (3) Valsalva maneuver.

Conclusions

CABG caused an impairment, reversible after 60 days, of cardiovascular autonomic function, with a maximal decrease on about the sixth day after surgery.
A role for Mer tyrosine kinase in αvβ5 integrin-mediated phagocytosis of apoptotic cells
Authors: Wu Yi , Singh Sukhwinder , Georgescu Maria-Magdalena , Birge Raymond B.
Published: January 2005

Efficient phagocytosis of apoptotic cells is crucial for many cellular processes. One of earliest signals to the phagocyte is the expression of phosphatidylserine (PS) on the outer surface of the apoptotic cell that provides a potent `eat-me' signal. Recognition of PS occurs either directly, via PS receptor (PS-R), or indirectly via αvβ5(3) integrin or Mer-family tyrosine kinases through the opsonizing proteins milk fat globule-EGF factor 8 protein (MFG-E8), or growth arrest specific factor-6 (Gas6), respectively. Because Mer and αvβ5 integrin share PS-dependent recognition signals, we investigated their post-receptor signaling cascades following receptor activation. Using a constitutively active form for Mer (CDMer) or Gas6 as a ligand to stimulate Mer, we found that Mer activation induced a post-receptor signaling cascade involving Src-mediated tyrosine phosphorylation of FAK on Tyr861, the recruitment of FAKTyr861 to the αvβ5 integrin, and increased formation of p130CAS/CrkII/Dock180 complex to activate Rac1. Coexpression of Mer with αvβ5 integrin had a synergistic effect on Rac1 activation, lamellipodial formation and the phagocytosis of apoptotic cells. Interestingly, Gas6 or CDMer failed to stimulate p130CAS tyrosine phosphorylation or phagocytosis in β5-deficient CS-1 cells or in mutant β5ΔC-expressing cells, suggesting that Mer is directionally and functionally linked to the integrin pathway. The present data indicate that receptors that recognize apoptotic cells in the context of PS functionally crosstalk to amplify intracellular signals to internalize apoptotic cells. Moreover, our data link another PS-dependent signal to the CrkII/Dock180/Rac1 module.
Cortical capture of microtubules and spindle polarity in budding yeast - where's the catch?
Authors: Huisman Stephen M. , Segal Marisa
Published: January 2005

In asymmetric divisions, the mitotic spindle must align according to the cell polarity axis. This is achieved through targeting astral microtubules emanating from each spindle pole to opposite cell cortex compartments. Saccharomyces cerevisiae is a powerful genetic model for dissection of this complex process. Intense research in this yeast has rendered detailed models for a program linking actin organization and spindle orientation along the mother-bud axis. This program requires the separate contributions of Kar9p, a protein guiding microtubules along polarized actin cables, and the polarity determinant Bud6p/Aip3 that marks sites for cortical capture at the bud tip and bud neck. In an added layer of complexity, cyclin-dependent kinase (Cdk) differentially regulates spindle pole function to dictate asymmetric spindle pole fate. Asymmetric contacts established by the spindle poles impart a further layer of extrinsic asymmetry restricting recruitment of Kar9p to the pole destined for the daughter cell. As a result, astral microtubules from a single pole are guided to the bud compartment after spindle assembly. Finally, Cdk might also translocate along astral microtubules in association with Kar9p to modulate microtubule-cortex interactions following spindle alignment. Insertion of the mitotic spindle into the bud neck is driven by the microtubule motor dynein. This process relies on the combined action of microtubule-plus-end-tracking proteins and kinesins that control the cell-cycle-dependent abundance of dynein at microtubule plus ends. Thus, this actin-independent pathway for spindle orientation might also be influenced by Cdk.
Frictionally excited thermoelastic instability in the presence of contact resistance
Authors: Afferrante L , Ciavarella M
Published: January 2005

In sliding systems, frictional heating generates a well-known instability above a certain critical speed Vcr, which is a function of geometrical and material properties only. Similar instabilities are known to occur in the static problem, driven by temperature differences, in the presence of thermal contact resistance. Thermal contact resistance at the interface has seldom been considered and gives rise to full coupling of the problem. Generally, the resistance decreases non-linearly when pressure is increased. Here, the critical condition (in terms of heat flux and sliding speed) for the stability of the uniform pressure solution for a half-plane in frictional contact with a rigid wall at fixed temperature is studied for a general resistance function R(p). It is found that the heat flux direction increases the instability as in the case of zero speed, i.e. when directed into the half-plane (which is the only distortive material), whereas frictional heating can have also a stabilizing effect, for a given heat flux, specifically when R(p) + pR'(p) < 0. Also, an isothermal critical speed has been defined, and the actual critical speed is found to be smaller or larger depending on the temperature difference sign. Longer wavelengths are always more unstable so that the critical wavelength is still dictated by the real size of the system.
Computer simulation of strain accumulation and hardening for pearlitic rail steel undergoing repeated contact
Authors: Kapoor A , Beynon J. H , Fletcher D I , Loo-Morrey M
Published: January 2005

This paper presents a validated model of plastic strain accumulation in railway rail steel under repeated wheel-rail contact. Such contacts subject the rails to severe stresses, taking the material local to the contact beyond yield, and leading to the incremental accumulation of plastic deformation (ratheting) as wheels pass. This process is at the root of several rail wear and rolling contact fatigue crack growth mechanisms. Existing plasticity models are inadequate for modelling the strain accumulation taking place in this material, which is under high hydrostatic compression (of the order of 1 GPa) and is severely anisotropic. The model described here is based on a ratcheting law derived from small-scale twin-disc rolling-sliding contact experiments and simulates tens of thousands of ratcheting cycles and the corresponding strain hardening in a few minutes on a personal computer. Results indicate that, to model these processes successfully, and to represent correctly the high levels of ductility seen in rail steels under compressive load, stress-strain data generated under high hydrostatic compression are required.
Boundary element analysis of contact problems using inverse techniques—linear and quadratic elements
Authors: Wang P , Becker A. A , Jones I. A , Hyde T. H
Published: January 2005

This paper presents an inverse boundary element (BE) technique to reconstruct the boundary conditions in contact regions using photoelastic measurement data consisting of the differences of the principal stresses and their orientations at interior points. The separate individual Cartesian stress components are then obtained using the conventional ‘forward’ boundary element method (BEM). Numerical experiments show that using linear elements instead of quadratic elements can reduce the sensitivity of the inverse BEM to the errors of photoelastic measurements and gives better results. A smoothing displacement scheme is further introduced to improve the accuracy of the reconstructed tractions. When up to 5, 10 and 20 per cent random ‘noise’ was added to the simulated measurement data, the results of the inverse BE analysis still show good agreement with reference solutions. An example using real photoelastic measurements on a simple specimen is also presented and the results are found to be encouraging.
Some analytical results for plane contact problems
Authors: Sackfield A , Truman C. E
Published: January 2005

Traditionally, two-dimensional elasticity problems have been solved using an Airy stress function or a Muskhelishvili complex potential approach. The principal advantage of the Muskhelishvili approach is that the interior stress field may be found directly from the boundary tractions, unlike the Airy approach where a degree of guesswork is necessary to obtain a suitable potential function. This paper demonstrates the equivalence of these two approaches to contact problems. The paper then extends the Muskhelishvili method to out-of-plane contact problems. To demonstrate the usefulness of this method, it is applied to two important problems motivated by fretting fatigue studies. The stick/slip behaviour of a Hertzian indenter, when the substrate is subjected to a bulk tensile stress field, is determined and the complete stress fields for both a flat-ended punch and a parabolic punch, when the punch is sliding in an out-of-plane direction, are found.
A consideration of the effects of the slip displacement on fretting fatigue behaviour
Authors: Dini D , Hills D. A
Published: January 2005

In this paper the possibility is explored that the slip displacement has an influence on the range of stresses experienced by a fretting contact. It is shown that this can have a first-order effect only for a sliding contact.
Surface-enhanced Raman scattering and SERRS imaging of phthalocyanine mixed films
Authors: AROCA R. , PIECZONKA N. , KAM A. P.
Published: January 2005

The objective of the present work is the study of the surface-enhanced spectroscopy of mixed thin solid films of metallophthalocyanine ( MPc ; M ≡ Cu , Co ) and bis(n-propylimido)perylene ( Bis - PTCDPr ) materials fabricated by vacuum co-evaporation onto silver island films. The surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) of neat Bis - PTCDPr , CuPc and CoPc were also recorded using visible 514.5 and 633 nm laser lines and near-infrared excitation at 780 nm. During the investigation it was found that the Raman scattering (RS) and resonance Raman scattering (RRS) spectra of CuPc and CoPc films were sensitive to the irradiance at the sample. To further explore the effect of local heating on the vibrational spectrum, a temperature dependence (between −180 and 200 °C) study was carried out using the 514.5 nm laser line with constant laser power. The overtones and combinations of the CuPc and CoPc molecules were also clearly observed in the RRS and SERRS spectra. The study of the SER(R)S spectra allowed us to conclude that the dyes of the mixed films were physically adsorbed onto the silver islands. It is also shown that, in mixed films, differences in the absorption properties can be used to tune into the spectrum of any one of the components of the mixture with the appropriate laser line. For the first time, SERRS mapping and global imaging of mixed films obtained with the 514.5 nm laser line are reported. Complementary information about the quality of the films, homogeneity and phase separation may be obtained using SERRS imaging.
Photochemical and photophysical behaviour of porphyrins and phthalocyanines irradiated with violet or ultraviolet light
Authors: TOKUMARU KATSUMI
Published: January 2005

Photochemical irradiation of porphyrins or phthalocyanines with violet or ultraviolet light absorbed by their second or higher absorption bands populates their higher excited states. These higher excited states generally dissipate very rapidly, but, competing with such rapid deactivation, often show unique behaviour different from the lowest excited states populated under visible light irradiation of the first absorption band, namely wavelength-dependent reactions or emission. The higher excited states often exhibit characteristic emission and enhanced reactivity in electron transfer, energy transfer and so on, competing with rapid deactivation. This paper attempts to summarize our work, perfomed particularly by means of femtosecond spectroscopy, and recent progress in this area.
Behavioral profiles and symptoms of autism in CHARGE syndrome: Preliminary Canadian epidemiological data
Authors: Smith Isabel M. , Nichols Shana L. , Issekutz Karina , Blake Kim
Published: February 2005

Individuals with CHARGE syndrome were identified through the Canadian Pediatric Surveillance Program (CPSP). From this population‐based cohort (n = 78), we present data on developmental and behavioral characteristics for the first 13 individuals (eight males, five females) for whom assessments are complete. Standardized parent questionnaires on development and behavior were followed by a structured telephone interview, with a specific emphasis on symptoms of autistic spectrum disorder (ASD). Preliminary results confirm that individuals with CHARGE syndrome have relatively low adaptive behavior skills, motor impairments being particularly significant. Most individuals did not present with significant behavior problems; however, evidence of ASD symptoms was judged to be moderate to strong in six of the ten children who were above the age of 4–5 years. Results are discussed with reference to the challenges inherent in the diagnosis of autism in individuals with sensory impairments, and to the implications for understanding the etiology of CHARGE syndrome and of ASD. © 2005 Wiley‐Liss, Inc.
Dual substrate biodegradation of a nonionic surfactant and pentachlorophenol by Sphingomonas chlorophenolica RA2
Authors: Bielefeldt Angela R. , Cort Todd
Published: February 2005

The simultaneous biodegradation of the nonionic surfactant Tween 20 (Tw20) and pentachlorophenol (PCP) by Sphingomonas chlorophenolica sp. Strain RA2 (RA2) was measured. As a sole substrate, Tw20 biodegradation was best described by the Contois kinetic model. During concurrent biodegradation of Tw20 and PCP, the biodegradation rates of Tw20 were not significantly affected by 50 or 100 mg/L PCP, but were significantly inhibited by 500 mg/L PCP. Decreases in cell yield in the presence of PCP suggest that PCP was acting as an uncoupler. Cultures were pre‐grown on PCP or Tw20 before degradation of PCP to evaluate enzyme induction effects, and long lags before PCP biodegradation after growth on Tw20 occurred. Although biokinetic models could accurately describe some of the data sets of RA2 growth and Tw20 and PCP degradation, finding a single set of kinetic parameters that predicted all dual substrate tests was not achieved. The complicating factors to modeling PCP and Tw20 interactions are described and may be more widely applicable to the biodegradation of toxic organic compounds in the presence of a biodegradable surfactant. ©2005 Wiley Periodicals, Inc.
Production of Desmodus rotundus salivary plasminogen activator α1 (DSPAα1) in tobacco is hampered by proteolysis
Authors: Schiermeyer Andreas , Schinkel Helga , Apel Stefanie , Fischer Rainer , Schillberg Stefan
Published: February 2005

The high fibrin specificity of Desmodus rotundus salivary plasminogen activator α1 (DSPAα1 or desmoteplase (INN)) makes it a promising candidate for the treatment of acute ischemic stroke. In the current study we explored the use of transgenic tobacco plants and BY‐2 suspension cells as alternative production platforms for this drug. Four different N‐terminal signal peptides, from plants and animals, were used to translocate the recombinant DSPAα1 protein to the endomembrane system. Intact recombinant DSPAα1 was produced in transgenic plants and BY‐2 cells, although a certain degree of degradation was observed in immunoblotted extracts. The choice of signal peptide had no major influence on the degradation pattern or recombinant protein accumulation, which reached a maximum level of 38 μg/g leaf material. N‐terminal sequencing of purified, His6‐tagged DSPAα1 revealed only minor changes in the position of signal peptide cleavage compared to the same protein expressed in Chinese hamster ovary cells. However, correctly processed recombinant DSPAα1 was also detected. The enzymatic activity of the recombinant protein was confirmed using an in vitro assay with unpurified and purified samples, demonstrating that plants are suitable for the production of functional DSPAα1. In contrast to whole plant cell extracts, no recombinant DSPAα1 was detected in the culture supernatant of transgenic BY‐2 cells. Further analysis showed that recombinant DSPAα1 is subject to proteolysis and that endogenous secreted BY‐2 proteases are responsible for DSPAα1 degradation in the culture medium. The addition of a highly concentrated protease inhibitor mixture or 5 mM EDTA reduced DSPAα1 proteolysis, improving the accumulation of intact product in the culture medium. Strategies to improve the plant cell suspension system for the production of secreted recombinant proteins are discussed. © 2005 Wiley Periodicals, Inc.
Unifying concept of DNA repair: The polymerase scanning hypothesis
Authors: Heddle John A. , Bielas Jason H.
Published: January 2005

According to a series of experiments on untransformed mouse embryonic fibroblasts, quiescent mouse cells lack global genomic repair (GGR) of premutagenic DNA damage. The gene used to assess mutation and premutagenic DNA damage was the lacI transgene incorporated permanently in the DNA in a λ shuttle vector. The transgene lacks mammalian transcription signals and thus is unexpressed in the cells. Although the cells conducted transcription‐coupled repair (TCR) of UV damage, the transgene was not repaired over a 4‐day interval. These cells are not terminally differentiated and can readily be induced to resume cellular division. In this article, we discuss the interpretation of these results and suggest a new hypothesis for DNA scanning, the mechanism by which cells discover DNA damage and initiate DNA repair. Our hypothesis, which we call the polymerase scanning hypothesis, is that GGR is initiated in very much the same way as TCR, by a polymerase complex encountering the damage. We call the two together polymersase‐coupled repair (PC repair). In the case of GGR, it would be the DNA replication complex during the S‐phase. This is, we suggest, the dominant mechanism of repair of DNA at low doses for untranscribed genes. Evidence contrary to this hypothesis exists, which we discuss, but it should be noted that existing hypotheses about DNA scanning and DNA repair cannot account for the results that we have obtained. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
A high resolution scheme for flows in open channels with arbitrary cross‐section
Authors: Aldrighetti E. , Zanolli P.
Published: February 2005

The aim of this paper is to present a numerical scheme to simulate unsteady, one‐dimensional flows in open channels with arbitrary cross‐section. This scheme is fully conservative of volume and momentum and preserves the non‐negativity of the water depth. The finite difference method derived is semi‐implicit in time and based on a space staggered grid. A high‐resolution technique, the flux limiter method, is implemented to control the accuracy of the proposed scheme. Our purpose is to achieve the precision and the stability of the method with respect to the regularity of the data. A few computational examples on classical test cases are given to illustrate the properties of the present method in terms of stability, accuracy and efficiency. Copyright © 2005 John Wiley & Sons, Ltd.
Energy balance, insulin‐related genes and risk of colon and rectal cancer
Authors: Slattery Martha L. , Murtaugh Maureen , Caan Bette , Ma Khe Ni , Neuhausen Susan , Samowitz Wade
Published: February 2005

Energy balance, or the ability to maintain body weight by balancing energy intake with energy expenditure, appears to be important in the etiology of colon cancer. One possible mechanism whereby energy balance may be associated with colorectal cancer is through its association with insulin. In our study, we evaluate the interaction between polymorphisms in 4 genes thought to be involved in insulin‐related functions and components of energy balance with risk of colorectal cancer. Data from 2 population‐based case‐control studies of colon and rectal cancer conducted in Utah and Northern California were used to evaluate associations between body mass index (BMI), physical activity, energy intake and sucrose‐to‐fiber ratio and a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide ‐202 of the IGFBP3, the G972R polymorphism of the IRS1 gene and the G1057D polymorphism of the IRS2 gene. A total of 1,346 incident colon cancer cases and 1,544 population‐based controls and 952 incident rectal cancer cases and 1,205 controls were available for analysis. Inconsistent associations were identified between BMI, physical activity, energy intake and insulin‐related genes. The 192/192 IGF1 genotype was associated with significant reduction in colon cancer risk among those with high physical activity (odds ratio [OR] 0.57; 95% confidence interval [CI] 0.39–0.83; p interaction 0.01). Although there was no significant pattern of interaction between either BMI or energy intake and polymorphisms assessed, specific sources of energy did appear to be more related to colon cancer risk in the presence of specific IRS2 and IGF1 genotypes. A high sucrose‐to‐fiber ratio increased risk of colon cancer in men who had the IRS2 DD genotype and among men who did not have the 192/192 IGF1 genotype. In summary, these data support the importance of components of energy balance in risk of colorectal cancer. Obesity, physical activity and energy intake appear to alter risk of colorectal cancer; however, the risk appears to be minimally influenced by genetic variants evaluated. © 2005 Wiley‐Liss, Inc.
Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB
Authors: Pozo‐Guisado Eulalia , Merino Jaime M. , Mulero‐Navarro Sonia , Lorenzo‐Benayas M. Jesús , Centeno Francisco , Alvarez‐Barrientos Alberto , Salguero Pedro M. Fernandez
Published: February 2005

Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF‐7 breast tumor cells by interfering with the estrogen receptor (ERaα)–dependent phosphoinositide 3‐kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES‐induced apoptosis. Apoptotic death by RES in MCF‐7 was mediated by Bcl‐2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl‐2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP‐ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF‐κB, a regulator of Bcl‐2 expression, and calpain protease activity, a regulator of NF‐κB, were both inhibited by RES. The patterns for NF‐κB and calpain activities followed that of PI3K and were inhibited by LY294002. NF‐κB inhibition coincided with diminished MMP‐9 activity and cell migration. These data suggest that RES‐induced apoptosis in MCF‐7 could involve an oxidative, caspase‐independent mechanism, whereby inhibition of PI3K signaling converges to Bcl‐2 through NF‐κB and calpain protease activity. Therefore, Bcl‐2 and NF‐κB could be considered potential targets for the chemopreventive activity of RES in estrogen‐responsive tumor cells. © 2005 Wiley‐Liss, Inc.