bluuebunny/crossref_metadata_2025 huggingface dataset:
Review: PCOS, insulin resistance and long-term risks for diabetes and vascular disease
Authors: Sattar Naveed
Published: March 2009

Insulin resistance is an important `upstream' driver for the reproductive and metabolic abnormalities in many women with polycystic ovarian syndrome (PCOS), in particular those who are overweight or obese. They frequently exhibit visceral adiposity, glucose intolerance, a dyslipidaemia which mirrors the pattern in type 2 diabetes, low-grade inflammation, and endothelial dysfunction. They are at elevated risk for type 2 diabetes (about two to four-fold relative to weight matched controls) and cardiovascular events (current best estimates at 50% higher compared with age, body mass index matched women without PCOS). Due to higher diabetes risk, women with PCOS who have other risk factors (e.g. obesity, family history of diabetes) would benefit from screening for diabetes, although the most efficient methods to do so require further investigation. Furthermore, despite the higher relative risk for coronary heart disease (CHD), absolute CHD risk is generally low in young women and thus routine lipid measurements or blood pressure in all women with PCOS would be redundant as such measurements will probably not alter clinical management. Rather, traditional risk measures should be restricted to those with significant other risk factors e.g. family history of premature vascular disease, diabetes. Finally, although recent trial evidence does not support a significant benefit of metformin in fertility treatments for PCOS, metformin does improve metabolic profile in the short term. However, longer-term formal trials of metformin are required to better understand its metabolic and vascular benefit in PCOS. Br J Diabetes Vasc Dis 2009;9:15—18
Drug use in gestational diabetes
Authors: Fraser Robert
Published: March 2009

There has been a traditional reluctance to recommend oral antidiabetic drugs for the management of hyperglycaemia in gestational diabetes mellitus. Recent publications suggest that both sulphonylureas and metformin may have a contribution to therapy in this condition and in particular the Metformin in Gestational Diabetes (MiG) trial provides good quality evidence that this drug might be particularly suitable when obesity is a factor in gestational diabetes. This article gives an overview of the rationale for use of oral antidiabetic agents in the treatment of gestational diabetes. Br J Diabetes Vasc Dis 2009;9:33—35
Immune Reconstitution Inflammatory Syndrome in a Resource-Poor Setting
Authors: Klotz Stephen A. , Aziz Mohammed Abdul , Girmai Woldemichael Mulugeta , Worku Mitku Mongistu , Handrich Mitchell
Published: March 2009

The immune reconstitution inflammatory syndrome (IRIS) associated with highly active antiretroviral therapy (HAART) was studied in rural Ethiopian HIV-infected patients. Review of 1002 charts in an outpatient clinic was conducted. The median CD4 count was 89 cells/mm3. Ninety-eight patients were hospitalized after initiation of HAART, of whom 74 were hospitalized for manifestations of IRIS (ie, 7% of patients on HAART). Of the 74 patients hospitalized with IRIS, 27 patients had tuberculosis; 12 patients, cryptococcal meningitis; 7 patients, toxoplasmosis; 6 patients, pneumonia and/or effusion; and 5 patients, Pneumocystis jiroveci pneumonia (PCP). Ten adult patients were admitted with gastroenteritis, heretofore not recognized as a manifestation of IRIS. Eighty-one percent of IRIS patients were hospitalized within 3 months of beginning HAART and 99% by 6 months. Of those hospitalized with IRIS, 4 patients (5%) died while in the hospital (3 with cryptococcal meningitis). Thirty-seven or 50% of those hospitalized with IRIS were lost to medical follow up, thus the mortality rate is likely a gross underestimate of the severity of IRIS. In resource-poor settings where the primary goal is to initiate HAART, IRIS may go unrecognized and have fatal consequences.
Review: Primary CNS lymphoma
Authors: Schlegel Uwe
Published: March 2009

Primary CNS lymphoma (PCNSL) accounts for 3% of all primary brain tumors with a median age at onset of about 62 years. In the vast majority of cases, PCNSL presents as unifocal or multifocal enhancing lesions on MRI, frequently adjacent to the ventricles. Stereotactic biopsy is the diagnostic procedure of choice revealing high-grade malignant non-Hodgkin's B-cell lymphoma in more than 90% of cases. Therapy is not evidence based. When eligible, patients should be included in clinical trials. In patients younger than 60 years cure is the aim. Polychemotherapy based on high-dose methotrexate (MTX) or alternatively high-dose chemotherapy with autologous stem cell rescue should be offered to patients eligible for this regimens. For patients over 60 years of age no curative regimen with acceptable toxicity has yet been established. An MTX-based chemotherapy, for example, in combination with temozolomide, is recommended. The role of radiotherapy as part of the initial treatment is not established; however, the combination of radiotherapy with MTX-based chemotherapy potentially leads to severe long-term neurotoxic sequelae. Therefore, radiotherapy as part of the initial therapy is not recommended by the author outside clinical trials. At relapse or in cases of refractory disease, patients will frequently benefit of salvage therapy, which depends on the initial treatment.
Review: Natalizumab in the treatment of multiple sclerosis
Authors: Yaldizli Özgür , Putzki Norman
Published: March 2009

Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk of sustained progression of disability by 42—54% over 2 years in its pivotal phase III trial (AFFIRM) in relapsing—remitting multiple sclerosis (RRMS). Natalizumab is generally well tolerated, but due to rare and potentially fatal side-effects, it was approved with a restricted-distribution format in 2006. Expert statements and the European Medical Agency recommend the use of natalizumab after failure of first-line disease-modifying therapies in patients with relapsing forms of MS. As part of the risk management plan, worldwide extensive safety programmes aim to provide more data on natalizumab safety in clinical practice. At the end of September 2008, 48 000 patients have received natalizumab and 18 000 patients are on treatment for at least 1 year. The assessment of risk and benefit is still ongoing.
Laser melting of HVOF coating: Effect of base material on residual stress formation
Authors: Arif A. F. M. , Yilbas B. S.
Published: March 2009

Laser heating of HVOF Diamalloy 1005 sprayed on to the base materials of steel and Ti–6Al–4V alloy is considered and the laser melting of the resulting coating is investigated. Thermal stress fields developed at different layers of the coating after the laser treatment are simulated using the finite element method (FEM) and the residual stress developed in the coating is measured using the curvature method. It is found that the thermal displacement predicted at the coating/base material interface is significantly higher for Ti–6Al–4V alloy than that for the steel base. The residual stress predicted for the coating corresponding to the steel base is higher than that of Ti–6Al–4V alloy base.
Genealogical Evidence and the Americanization of European Family Names
Authors: Picard Marc
Published: March 2009

AbstractThe purpose of this study is to compare the data on the Americanization of European family names presented in Hanks (2003) with the information that can currently be garnered from the plethora of genealogical websites that have sprung up in the recent past. The results show (1) that many of the origins he proposes fail to conform to the evidence found on those websites, and (2) that most of the surnames which he qualifies as "puzzling" or unexplained can be readily accounted for on the basis of this same type of evidence.
Regulated release and functional modulation of junctional adhesion molecule A by disintegrin metalloproteinases
Authors: Koenen Rory R. , Pruessmeyer Jessica , Soehnlein Oliver , Fraemohs Line , Zernecke Alma , Schwarz Nicole , Reiss Karina , Sarabi Alisina , Lindbom Lennart , Hackeng Tilman M. , Weber Christian , Ludwig Andreas
Published: March 2009

Junctional adhesion molecule A (JAM-A) is a transmembrane adhesive glycoprotein that participates in the organization of endothelial tight junctions and contributes to leukocyte transendothelial migration. We demonstrate here that cultured endothelial cells not only express a cellular 43-kDa variant of JAM-A but also release considerable amounts of a 33-kDa soluble JAM-A variant. This release is enhanced by treatment with proinflammatory cytokines and is associated with the down-regulation of surface JAM-A. Inhibition experiments, loss/gain-of-function experiments, and cleavage experiments with recombinant proteases indicated that cleavage of JAM-A is mediated predominantly by the disintegrin and metalloproteinase (ADAM) 17 and, to a lesser extent, by ADAM10. Cytokine treatment of mice increased JAM-A serum level and in excised murine aortas increased ADAM10/17 activity correlated with enhanced JAM-A release. Functionally, soluble JAM-A blocked migration of cultured endothelial cells, reduced transendothelial migration of isolated neutrophils in vitro, and decreased neutrophil infiltration in a murine air pouch model by LFA-1– and JAM-A–dependent mechanisms. Therefore, shedding of JAM-A by inflamed vascular endothelium via ADAM17 and ADAM10 may not only generate a biomarker for vascular inflammation but could also be instrumental in controlling JAM-A functions in the molecular zipper guiding transendothelial diapedesis of leukocytes.
Preclinical transfusion-dependent humanized mouse model of β thalassemia major
Authors: Huo Yongliang , McConnell Sean C. , Ryan Thomas M.
Published: March 2009

A preclinical humanized mouse model of β thalassemia major or Cooley anemia (CA) was generated by targeted gene replacement of the mouse adult globin genes in embryonic stem cells. The mouse adult α and β globin genes were replaced with adult human α globin genes (α2α1) and a human fetal to adult hemoglobin (Hb)–switching cassette (γHPFHδβ0), respectively. Similar to human infants with CA, fully humanized mice survived postnatally by synthesizing predominantly human fetal Hb, HbF (α2γ2), with a small amount of human minor adult Hb, HbA2 (α2δ2). Completion of the human fetal to adult Hb switch after birth resulted in severe anemia marked by erythroid hyperplasia, ineffective erythropoiesis, hemolysis, and death. Similar to human patients, CA mice were rescued from lethal anemia by regular blood transfusion. Transfusion corrected the anemia and effectively suppressed the ineffective erythropoiesis, but led to iron overload. This preclinical humanized animal model of CA will be useful for the development of new transfusion and iron chelation regimens, the study of iron homeostasis in disease, and testing of cellular and genetic therapies for the correction of thalassemia.
A proteomic approach for studying insect phylogeny: CAPA peptides of ancient insect taxa (Dictyoptera, Blattoptera) as a test case
Authors: Roth Steffen , Fromm Bastian , Gäde Gerd , Predel Reinhard
Published: March 2009

Background

Neuropeptide ligands have to fit exactly into their respective receptors and thus the evolution of the coding regions of their genes is constrained and may be strongly conserved. As such, they may be suitable for the reconstruction of phylogenetic relationships within higher taxa. CAPA peptides of major lineages of cockroaches (Blaberidae, Blattellidae, Blattidae, Polyphagidae, Cryptocercidae) and of the termiteMastotermes darwiniensiswere chosen to test the above hypothesis. The phylogenetic relationships within various groups of the taxon Dictyoptera (praying mantids, termites and cockroaches) are still highly disputed.

Results

Tandem mass spectrometry of neuropeptides from perisympathetic organs was used to obtain sequence data of CAPA peptides from single specimens; the data were analysed by Maximum Parsimony and Bayesian Interference. The resulting cladograms, taking 61 species into account, show a topology which is in general agreement with recent molecular and morphological phylogenetic analyses, including the recent phylogenetic arrangement placing termites within the cockroaches. When sequence data sets from other neuropeptides, viz. adipokinetic hormones and sulfakinins, were included, the general topology of the cladogram did not change but bootstrap values increased considerably.

Conclusion

This study represents the first comprehensive survey of neuropeptides of insects for solely phylogenetic purposes and concludes that sequences of short neuropeptides are suitable to complement molecular biological and morphological data for the reconstruction of phylogenetic relationships.
Building blocks for meta-synthesis: data integration tables for summarising, mapping, and synthesising evidence on interventions for communicating with health consumers
Authors: Ryan Rebecca E , Kaufman Caroline A , Hill Sophie J
Published: March 2009

Background

Systematic reviews have developed into a powerful method for summarising and synthesising evidence. The rise in systematic reviews creates a methodological opportunity and associated challenges and this is seen in the development of overviews, or reviews of systematic reviews. One of these challenges is how to summarise evidence from systematic reviews of complex interventions for inclusion in an overview. Interventions for communicating with and involving consumers in their care are frequently complex. In this article we outline a method for preparing data integration tables to enable review-level synthesis of the evidence on interventions for communication and participation in health.

Methods and Results

Systematic reviews published by the Cochrane Consumers and Communication Review Group were utilised as the basis from which to develop linked steps for data extraction, evidence assessment and synthesis. The resulting output is called a data integration table. Four steps were undertaken in designing the data integration tables: first, relevant information for a comprehensive picture of the characteristics of the review was identified from each review, extracted and summarised. Second, results for the outcomes of the review were assessed and translated to standardised evidence statements. Third, outcomes and evidence statements were mapped into an outcome taxonomy that we developed, using language specific to the field of interventions for communication and participation. Fourth, the implications of the review were assessed after the mapping step clarified the level of evidence available for each intervention.

Conclusion

The data integration tables represent building blocks for constructing overviews of review-level evidence and for the conduct of meta-synthesis. Individually, each table aims to improve the consistency of reporting on the features and effects of interventions for communication and participation; provides a broad assessment of the strength of evidence derived from different methods of analysis; indicates a degree of certainty with results; and reports outcomes and gaps in the evidence in a consistent and coherent way. In addition, individual tables can serve as a valuable tool for accurate dissemination of large amounts of complex information on communication and participation to professionals as well as to members of the public.
An exploratory study to evaluate the utility of an adapted Mother Generated Index (MGI) in assessment of postpartum quality of life in India
Authors: Nagpal Jitender , Dhar Rinku Sen Gupta , Sinha Swati , Bhargava Vijaylakshmi , Sachdeva Aarti , Bhartia Abhishek
Published: March 2009

Background

Given the postulated advantages of mother generated index (MGI) in incorporating the patients' viewpoint and in the absence of a validated India specific postpartum quality of life assessment tool we proposed to evaluate the utility of an adapted Mother-Generated-Index in assessing postpartum quality of life (PQOL) in India.

Methods

The study was integrated into a community survey conducted in one district of Delhi by two-stage cluster randomized sampling to recruit women who delivered in the last 6 months. PQOL was assessed using MGI. Physical morbidity and Edinburgh- postnatal-depression-scale (EPDS) were also recorded for validation purposes.

Results

All subjects (249 of 282 eligible) participating in the survey were approached for the MGI evaluation which could be administered to 195 subjects due to inadequate comprehension or refusal of consent. A trend towards lower scores in lower socioeconomic stratum was observed (Primary index score-2.9, 3.7 and 4.0 in lower, middle and higher strata; Secondary Index Score-2.6, 3.2 and 3.0 in lower, middle and higher strata). 59.4% mothers had scores suggestive of possible depression (EPDS; n = 172). Primary index score had a good correlation with validator scores like EPDS (p = 0.024) and number of physical problems (p = 0.022) while the secondary index score was only associated with EPDS score (p = 0.020).

Conclusion

The study documents that the MGI, with its inherent advantages, is a potentially useful tool for postpartum quality of life evaluation in India especially in the absence of an alternative pre-validated tool.
The feasibility of reservoir monitoring using time-lapse marine CSEM
Authors: Orange Arnold , Key Kerry , Constable Steven
Published: March 2009

Monitoring changes in hydrocarbon reservoir geometry and pore-fluid properties that occur during production is a critical part of estimating extraction efficiency and quantifying remaining reserves. We examine the applicability of the marine controlled-source electromagnetic (CSEM) method to the reservoir-monitoring problem by analyzing representative 2D models. These studies show that CSEM responses exhibit small but measureable changes that are characteristic of reservoir-depletion geometry, with lateral flooding producing a concave-up depletion-anomaly curve and bottom flooding producing a concave-down depletion-anomaly curve. Lateral flooding is also revealed by the spatial-temporal variation of the CSEM anomaly, where the edge of the response anomaly closely tracks the retreating edge of the flooding reservoir. Measureable changes in CSEM responses are observed when 10% of the resistive reservoir is replaced by conductive pore fluids. However, to avoid corrupting the relatively small signal changes associated with depletion, the acquisition geometry must be maintained to a fraction of a percent accuracy. Additional factors, such as unknown nearby seafloor inhomogeneities and variable seawater conductivity, can mask depletion anomalies if not accounted for during repeat monitoring measurements. Although addressing these factors may be challenging using current exploration CSEM practices, straightforward solutions such as permanent monuments for seafloor receivers and transmitters are available and suggest the method could be utilized with present-day technology.
Automatic nonhyperbolic velocity analysis
Authors: Abbad Brahim , Ursin Bjørn , Rappin Didier
Published: March 2009

The stacking of long-offset seismic data requires a nonhyperbolic traveltime function that depends on two-way traveltime, normal moveout (NMO) velocity and effective anellipticity. Based on a standard fractional approximation, a new parameterization in slowness-squared parameters provides optimal sampling of the NMO velocity and anellipticity. The automatic nonhyperbolic velocity analysis is performed with a normalized bootstrapped differential semblance (BDS) coherency estimator that leads to enhanced resolution in velocity spectra compared to differential semblance. Reflection wavelet centering inside time gates results in improved estimates of the two-way time and reduced bias in estimates of the NMO velocity and anellipticity. Generalized Dix equations give estimates of apparent interval thickness, velocity and anellipticity. The interval parameters will fit a homogeneous transversely isotropic medium with a vertical symmetry axis (a VTI medium) or an isotropic layer with a linear velocity gradient. The algorithm is implemented in a two-step strategy. A coarse hyperbolic velocity analysis that identifies events in the gather and estimates a velocity law for applying thetruncation is followed by a dense nonhyperbolic search to infer the physical parameters required for time processing of PP-wave data. The algorithm outputs an automatic stack and later-ally varying moveout velocity and anellipticity maps that can be used for subsequent time processing. Two attribute maps, the BDS map and its derivative, are also computed. These contain the fingerprints of the key reflectors and can be used in structural interpretation. Automatic nonhyperbolic velocity analysis is tested on a synthetic gather and a real data set from the North Sea. Nonhyperbolic parameter search shows an en-hanced estimate of the processing parameters, velocity and anellipticity, and improved quality of the stacked section com-pared with the result from hyperbolic search. The interval moveout velocity maps demonstrate a good match with the reflector positions in the obtained sections and show a great correlation when compared with the results of more advanced processing. The interval anellipticity map is also important for enhanced time processing and resolving the time-depth conversion problem, but the parameter is meaningless when the anisotropy is important or when the aperture is small, mainly for deep reflectors.
Designing stable extrapolators for explicit depth extrapolation of 2D and 3D wavefields using projections onto convex sets
Authors: Mousa Wail A. , van der Baan Mirko , Boussakta Said , McLernon Desmond C.
Published: March 2009

We have developed a robust algorithm for designing explicit depth extrapolation operators using the projections-onto-convex-sets (POCS) method. The operators are optimal in the sense that they satisfy all required extrapolation design characteristics. In addition, we propose a simple modification of the POCS algorithm (modified POCS, or MPOCS) that further enhances the stability of extrapolated wavefields and reduces the number of iterations required to design such operators to approximately 2% of that required for the basic POCS design algorithm. Various synthetic tests show that 25-coefficient 1D extrapolation operators, which have 13 unique coefficients, can accommodate dip angles up to 70°. We migrated the SEG/EAGE salt model data with the operators and compare our results with images obtained via extrapolators based on modified Taylor series and with wavefield extrapolation techniques such as phase shift plus interpolation (PSPI) and split-step Fourier. The MPOCS algorithm provides practically stable depth extrapolators. The resulting migrated section is comparable in quality to an expensive PSPI result and visibly outperforms the other two techniques. Strong dips and subsalt structures are imaged clearly. Finally, we extended the 1D extrapolator design algorithm, using MPOCS for 2D extrapolation, to the 2D case to perform 3D extrapolation; the result is a perfect circularly symmetric migration impulse response.
Age Dependence of Early Symptomatic Vertebral Fracture with High-Dose Glucocorticoid Treatment for Collagen Vascular Diseases
Authors: Tatsuno Ichiro , Sugiyama Takao , Suzuki Sawako , Yoshida Tomohiko , Tanaka Tomoaki , Sueishi Makoto , Saito Yasushi
Published: March 2009

Objectives: Collagen vascular diseases requiring treatment with high-dose glucocorticoids are frequently complicated by vertebral fracture. We investigated the incidence of symptomatic vertebral fractures for 20 yr among patients who were treated with high-dose glucocorticoids in the Chiba-Shimoshizu Rheumatic Cohort.

Methods: A total of 2631 patients with collagen vascular diseases (aged ≥18 yr) was registered between 1986 and 2006. The prevalence of symptomatic vertebral fracture was compared between the high-dose glucocorticoid group newly treated with high-dose glucocorticoids (≥20 mg/d prednisolone equivalent) (n = 700), and the non-glucocorticoid controls not treated with glucocorticoids (n = 194).

Results: During the 20-yr study period, symptomatic vertebral fractures occurred more frequently in the high-dose glucocorticoid group (23.9%) than in the non-glucocorticoid controls (2.6%). According to a Kaplan-Meier analysis, the cumulative incidence of symptomatic vertebral fracture was significantly higher in the high-dose glucocorticoid group than in the non-glucocorticoid controls (P < 0.001). Stratified into age quartiles of the high-dose glucocorticoid group (age 18–31, 32–47, 48–59, and 60–88 yr), the patients had a markedly increased incidence of symptomatic vertebral fracture with aging. The hazard ratios were also significantly higher in the older age quartile of 60–68 than in the younger age quartile of 32–47 (P < 0.001 for trend). The hazard ratio was 26-fold higher in patients aged 60–88 than in patients aged 18–31 (P < 0.01). In the group with fractures, the treatment duration before fracture was negatively associated with the initial age (r = −0.6587; P < 0.001).

Conclusions: The prevalence of symptomatic vertebral fractures was higher in the patients treated with high-dose glucocorticoids than the untreated controls. Vertebral fractures were age dependent in patients treated with high-dose glucocorticoids. Treatment duration before fracture incidence was significantly shorter in the older patients.
KRAB zinc-finger proteins localise to novel KAP1-containing foci that are adjacent to PML nuclear bodies
Authors: Briers Stephanie , Crawford Catherine , Bickmore Wendy A. , Sutherland Heidi G.
Published: March 2009

The KRAB-zinc finger proteins (KRAB-ZFPs) represent a very large, but poorly understood, family of transcriptional regulators in mammals. They are thought to repress transcription via their interaction with KRAB-associated protein 1 (KAP1), which then assembles a complex of chromatin modifiers to lay down histone marks that are associated with inactive chromatin. Studies of KRAB-ZFP/KAP1-mediated gene silencing, using reporter constructs and ectopically expressed proteins, have shown colocalisation of both KAP1 and repressed reporter target genes to domains of constitutive heterochromatin in the nucleus. However, we show here that although KAP1 does indeed become recruited to pericentric heterochromatin during differentiation of mouse embryonic stem (ES) cells, endogenous KRAB-ZFPs do not. Rather, KRAB-ZFPs and KAP1 relocalise to novel nucleoplasmic foci that we have termed KRAB- and KAP1-associated (KAKA) foci. HP1s can also concentrate in these foci and there is a close spatial relationship between KAKA nuclear foci and PML nuclear bodies. Finally, we reveal differential requirements for the recruitment of KAP1 to pericentric heterochromatin and KAKA foci, and suggest that KAKA foci may contain sumoylated KAP1 – the form of the protein that is active in transcriptional repression.
βPIX-activated Rac1 stimulates the activation of phospholipase D, which is associated with exocytosis in neuroendocrine cells
Authors: Momboisse Fanny , Lonchamp Etienne , Calco Valerie , Ceridono Mara , Vitale Nicolas , Bader Marie-France , Gasman Stéphane
Published: March 2009

Rho GTPases are crucial regulators of actin cytoskeletal rearrangements and play important roles in many cell functions linked to membrane trafficking processes. In neuroendocrine cells, we have previously demonstrated that RhoA and Cdc42 mediate part of the actin remodelling and vesicular trafficking events that are required for the release of hormones by exocytosis. Here, we investigate the functional importance of Rac1 for the exocytotic reaction and dissect the downstream and upstream molecular events that might integrate it to the exocytotic machinery. Using PC12 cells, we found that Rac1 is associated with the plasma membrane and is activated during exocytosis. Silencing of Rac1 by siRNA inhibits hormone release, prevents secretagogue (high K+)-evoked phospholipase D1 (PLD1) activation and blocks the formation of phosphatidic acid at the plasma membrane. We identify βPix as the guanine nucleotide-exchange factor integrating Rac1 activation to PLD1 and the exocytotic process. Finally, we show that the presence of the scaffolding protein Scrib at the plasma membrane is essential for βPix/Rac1-mediated PLD1 activation and exocytosis. As PLD1 has recently emerged as a promoter of membrane fusion in various exocytotic events, our results define a novel molecular pathway linking a Rho GTPase, Rac1, to the final stages of Ca2+-regulated exocytosis in neuroendocrine cells.
Endocytosis of flotillin-1 and flotillin-2 is regulated by Fyn kinase
Authors: Riento Kirsi , Frick Manfred , Schafer Ingmar , Nichols Benjamin J.
Published: March 2009

Flotillin-1 and flotillin-2 co-assemble into plasma membrane microdomains that are involved in the endocytosis of molecules such as glycosyl phosphatidylinositol (GPI)-linked proteins. Previous studies suggest that budding of flotillin microdomains from the plasma membrane is a tightly regulated process. Here, we demonstrate that endocytosis of flotillins is regulated by the Src family kinase Fyn. The Src kinase inhibitor PP2 prevents EGF-induced flotillin internalisation, and EGF-induced internalisation does not occur in SYF cells lacking Src, Yes and Fyn. Expression of Fyn, but not Src or Yes, restores EGF-induced internalisation in SYF cells. Expression of an active form of Fyn but not other Src kinases is sufficient to induce redistribution of flotillins from the plasma membrane to late endosomes and lysosomes. Using two partial Fyn constructs that form a functional kinase upon addition of rapamycin to cells, we show that flotillin internalisation from the plasma membrane occurs shortly after Fyn activation. Tyr160 in flotillin-1 and Tyr163 in flotillin-2 are directly phosphorylated by Fyn, and mutation of these residues to phenylalanine prevents Fyn-induced flotillin internalisation. Uptake of the GPI-linked protein CD59 is reduced by expression of the phenylalanine-mutated flotillins. These data establish uptake of flotillin microdomains as a tyrosine-kinase-regulated endocytic process.
TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin
Authors: Coisy-Quivy Marjorie , Touzet Olivia , Bourret Annick , Hipskind Robert A. , Mercier Jacques , Fort Philippe , Philips Alexandre
Published: March 2009

The contractile activity of striated muscle depends on myofibrils that are highly ordered macromolecular complexes. The protein components of myofibrils are well characterized, but it remains largely unclear how signaling at the molecular level within the sarcomere and the control of assembly are coordinated. We show that the Rho GTPase TC10 appears during differentiation of human primary skeletal myoblasts and it is active in differentiated myotubes. We identify obscurin, a sarcomere-associated protein, as a specific activator of TC10. Indeed, TC10 binds directly to obscurin via its predicted RhoGEF motif. Importantly, we demonstrate that obscurin is a specific activator of TC10 but not the Rho GTPases Rac and Cdc42. Finally, we show that inhibition of TC10 activity by expression of a dominant-negative mutant or its knockdown by expression of specific shRNA block myofibril assembly. Our findings reveal a novel signaling pathway in human skeletal muscle that involves obscurin and the Rho GTPase TC10 and implicate this pathway in new sarcomere formation.
Uncertainty due to experimental conditions in co-ordinate measuring machines
Authors: Lobato H , Ferri C , Faraway J , Orchard N
Published: March 2009

Any measurement method of a physical quantity cannot provide an exact unequivocal result owing to the infinite amount of information necessary to characterize fully both the physical quantity to be measured and the measuring process. Therefore, a quantitative indication of the quality of a measurement result needs to be given to enable its reliable use. Uncertainty is one such indication. Provision of incorrect uncertainty statements for measurements performed by a co-ordinate measuring machine (CMM) may lead to very serious economic implications. In this study, the uncertainty of CMM measurements is estimated by a single parameter accounting for both systematic and random errors. The effects that environmental conditions (temperature), discretionary set-up parameters (probe extension, stylus length), and measuring plan decisions (number of points) have on uncertainty of measurements are then investigated. Interactions between such factors are also shown to be significant.
Innovative virtual prototyping environment for reconfigurable manufacturing system engineering
Authors: Vera D A , West A , Harrison R
Published: March 2009

A new approach to the design and implementation of virtual prototyping environments (VPEs), aimed at providing support for the engineering of flexible machine technologies (referred to as reconfigurable manufacturing systems (RMSs)) is presented. The research is focused on two aspects of VPE tool development, namely on ensuring the consistency between real- and virtual-system architectures, design tools, and design processes and on maximizing the potential of three-dimensional computer-based virtual models as a basis for distributed engineering collaboration. A component-based (CB) approach to VPE tool design and implementation is proposed, which radically contrasts with approaches commonly adopted by both the commercial and academic VPE developers. The VPE developed in the context of this research should ultimately enable more effective management of RMS complex engineering life cycles by engineering partners who are globally distributed.
State-of-art-review of electrochemical honing of internal cylinders and gears
Authors: Jain N K , Ramlal Naik L , Dubey A K , Shan H S
Published: March 2009

This paper is an attempt to present a state-of-the-art review of two major applications of electrochemical honing (ECH) for internal cylinders and gears, which are the most commonly used parts in numerous engineering applications. ECH is a hybrid process of electrochemical machining (ECM) and mechanical honing, combining the fast material removal capabilities of ECM and controlled functional surface generating capabilities of mechanical honing in a single operation. ECH is a precision micro-finishing process capable of producing excellent surface quality having a cross-hatch lay pattern required for lubricating oil retention, compressive residual stresses required for the components subjected to cyclic loading, and completely stress-free surfaces. Furthermore, it provides these benefits productively. It makes ECH an ideal choice for superfinishing, improving the surface integrity, and increasing the service life of the critical components such as internal cylinders, transmission gears, carbide bushings and sleeves, rollers, petrochemical reactors, moulds and dies, gun barrels, etc., most of which are made of very hard and/or tough, wear-resistant materials generally susceptible to heat distortions. Consequently, ECH finds widespread use in the automobile, avionics, petrochemical, power generation, and fluid power industries. This paper presents a detailed description of the process principle, parameters, capabilities, equipment details, applications, and comprehensive literature review of past research work on the ECH of internal cylinders and gears along with some directions for future research with an objective to revive the interest of the global research community to mature this process further.
Study of the autoignition combustion operating region of a small two-stroke engine
Authors: Wijesinghe J , Hong G
Published: March 2009

A limited load region is one of the main problems of homogeneous charge compression ignition. In the work reported in this paper the autoignition (AI) load region specific to a small two-stroke engine has been investigated. The objective was to gain a better understanding regarding the characteristics of the AI operating regime by studying the combustion stability and exhaust emissions. AI combustion was achieved by trapping hot exhaust gases inside the cylinder with an exhaust throttle valve. The intake throttle, exhaust throttle, and fuelling rate were manually adjusted to obtain the required engine operating points. The nature of combustion and implications of exhaust emissions have been discussed in relation to the load regions of AI operation. The operation of AI in the medium- to high-load ranges demonstrated a higher degree of cyclic stability. In contrast with this, AI operation at lower-loads demonstrated a higher degree of cyclic instability.
Determining the deterioration cost for railway tracks
Authors: Öberg J , Andersson E
Published: March 2009

The cost of maintaining and renewing railway tracks affected by traffic-dependent deterioration is considerable. It is important not only to have proper maintenance regimes, but also to have knowledge of the interaction between vehicles and track in order to reduce the deterioration of both.

In a joint project between Banverket (Swedish Rail Administration) and KTH (Royal Institute of Technology, Stockholm), a model for track deterioration is developed, considering track settlement, component fatigue, abrasive wear, and rolling contact fatigue of rails. The basis of the model is taken from what is considered as state-of-the-art knowledge. The model is used as a basis for a proposed new track access charging regime for Banverket, able to differ between vehicle types based on their characteristics and tendency to deteriorate the tracks.

The model is implemented in an Excel® environment and applied to Swedish mainline traffic and vehicles. Using representative vehicle characteristics in determining track deterioration, it is predicted that there are large differences between different vehicles regarding their deterioration of the tracks. The model predicts axle load, unsprung mass, and wheelset steering capability as decisive for track deterioration. The model is believed to predict realistic results also for heavy-haul rail operations.
Wear and energy-saving freight bogie designs with rubber primary springs: principles and experiences
Authors: Hecht M
Published: March 2009

The traditional radial steering bogie with swing hanger links is known to be track-friendly but heavy, and expensive in investment and maintenance costs. Whereas the actual bogies with longitudinal stiff axle guidance such as Y25 cause severe wear on wheels and rails in curves, and also develop high running resistance in curves.

Bogies with rubbers springs like double rubber ring spring (DRRS), Leicht und LaermArm (LEILA) low weight and low noise, and Gigabox are a new feature with good behaviour in curves and on straight tracks. Good experience over many years with DRRS and 35 t axle load on the German Rheinisch Westfaelische Elektrizitaetswerke (RWE) coal line prove its benefits. For the new designs, LEILA and Gigabox, which are being introduced into the market now, even higher benefits can be demonstrated. The principle design features and the benefits regarding lateral track forces, wear, and traction resistance are evident. Also noise behaviour is an increasing demand for freight operation.
A low-power wireless sensing device for remote inspection of bolted joints
Authors: Mascarenas D L , Park G , Farinholt K M , Todd M D , Farrar C R
Published: March 2009

A new bolted-joint monitoring system is presented. This system consists of structural joint members equipped with piezoelectric (PZT) sensing elements and a wireless impedance device for data acquisition and communication. PZT enhanced washers are used to continuously monitor the condition of the joint by monitoring its dynamic characteristics. The mechanical impedance matching between the PZT enhanced devices and the joint connections is used as a key feature to monitor the preload changes and to prevent further failure. The dynamic response is readily measured using the electromechanical coupling property of the PZT patch, in which its electrical impedance is directly coupled with the mechanical impedance of the structure. A new miniaturized and portable impedance measuring device is implemented for the practical implementation of the proposed method. The proposed system can be used for the remote and rapid inspection of bolt tension and connection damage. Both theoretical modelling and experimental verification are presented to demonstrate the effectiveness of the proposed concept.
Application of the modified reduced-order aerodynamics modelling approach to aeroelastic analysis
Authors: Shahverdi H , Nobari A S , Haddadpour H , Behbahani-Nejad M
Published: March 2009

This study presents the application of the Proposed Modified Reduced-Order Aerodynamics Modelling approach for aeroelastic analysis based on the boundary element method (BEM) as a novel approach. The used BEM has the capability to capture the thickness effect and geometric complexity of a general three-dimensional model. In this approach the reduced-order aerodynamic model is defined through the eigenvalue problem of unsteady flow based on the unknown wake singularities. Based on the used aerodynamic model an explicit algebraic form of the aeroelastic equations is derived that reduces computational efforts and complexity. This special feature enables us to determine the aeroelastic instability directly via eigenanalysis of the aeroelastic problem. The eigenanalysis and reduced-order modelling of unsteady flow over a NACA 0012 airfoil are performed as an example and the results are compared with those obtained from conventional reduced-order modelling (CROM) method. The obtained results demonstrate the accuracy and superior efficiency of the present method over the CROM method. The method was then applied to the aeroelastic analyses of a typical section, in order to show the procedure of driving the explicit algebraic form. Furthermore, to illustrate the capability of the method in the handling of the three-dimensional problems, aeroelastic results for a wing are presented and compared with the results of the Theodorsen's aerodynamic theory.
Approximate closed-form solutions of realistic true proportional navigation guidance using the Adomian decomposition method
Authors: Garai T , Mukhopadhyay S , Ghose D
Published: March 2009

Approximate closed-form solutions of the non-linear relative equations of motion of an interceptor pursuing a target under the realistic true proportional navigation (RTPN) guidance law are derived using the Adomian decomposition method in this article. In the literature, no study has been reported on derivation of explicit time-series solutions in closed form of the non-linear dynamic engagement equations under the RTPN guidance. The Adomian method provides an analytical approximation, requiring no linearization or direct integration of the non-linear terms. The complete derivation of the Adomian polynomials for the analysis of the dynamics of engagement under RTPN guidance is presented for deterministic ideal case, and non-ideal dynamics in the loop that comprises autopilot and actuator dynamics and target manoeuvre, as well as, for a stochastic case. Numerical results illustrate the applicability of the method.
A numerical study of failure mechanisms in the cemented resurfaced femur: Effects of interface characteristics and bone remodelling
Authors: Pal B , Gupta S , New A M
Published: March 2009

Failure mechanisms of the resurfaced femoral head include femoral neck fracture in the short term and stress shielding and implant loosening in the long term. In this study, finite element simulations of the resurfaced femur considering a debonded implant—cement interface, variable stem—bone interface conditions, and bone remodelling were used to study load transfer within the resurfaced femur and to investigate its relationship with known failure mechanisms. Realistic three-dimensional finite element models of an intact and resurfaced femur were used. Various conditions at the interface between the stem of the prosthesis and the bone were considered. Loading conditions included normal walking and stair climbing. For all stem—bone contact conditions, the tensile stresses in the cement mantle varied between 1 MPa and 5.4 MPa, except near the distal rim of the resurfacing component where they reached 5.4—7 MPa. In the case of full stem—bone contact, high von Mises stresses (114—121 MPa) were generated in the implant at the stem—cup junction. These stresses were considerably reduced (maximum von Mises stress, 76 MPa) where a gap was present at the stem—bone interface. Resurfacing led to strain shielding of the bone of the femoral head (20—75 per cent strain reductions) and periprosthetic bone resorption (50—80 per cent bone density reductions) for all interface stem—bone contact conditions. In the lateral femoral head and the proximal femoral shaft around the trochantric region, bone density reductions varied between 10 per cent and 50 per cent. Bone apposition was observed in the inferior—medial part of the femoral head and proximal femoral neck region. For full stem—bone contact, more load was transferred through the stem to the surrounding bone, exacerbating strain shielding. Although femoral hip resurfacing conserves bone stock at the primary operation, strain shielding and periprosthetic bone resorption might lead to eventual loosening over time. Post-operatively, the resurfacing procedure generated elevated strains (0.50—0.75 per cent strain) in the proximal femoral neck—component junction irrespective of the variation in interface conditions, indicating an initial risk of femoral neck fracture. Subsequent to bone remodelling, this strain concentration was considerably reduced (0.35—0.50 per cent strain), lowering the risk of neck fracture. In order to reduce the potential risk of neck fracture, patients should avoid activities which might induce high loading of the hip during the early post-operative period to allow the bone around the proximal femoral neck to remodel and heal.
Magnetic resonance elastography hardware design: A survey
Authors: Tse Z T H , Janssen H , Hamed A , Ristic M , Young I , Lamperth M
Published: March 2009

Magnetic resonance elastography (MRE) is an emerging technique capable of measuring the shear modulus of tissue. A suspected tumour can be identified by comparing its properties with those of tissues surrounding it; this can be achieved even in deep-lying areas as long as mechanical excitation is possible. This would allow non-invasive methods for cancer-related diagnosis in areas not accessible with conventional palpation. An actuating mechanism is required to generate the necessary tissue displacements directly on the patient in the scanner and three different approaches, in terms of actuator action and position, exist to derive stiffness measurements. However, the magnetic resonance (MR) environment places considerable constraints on the design of such devices, such as the possibility of mutual interference between electrical components, the scanner field, and radio frequency pulses, and the physical space restrictions of the scanner bore. This paper presents a review of the current solutions that have been developed for MRE devices giving particular consideration to the design criteria including the required vibration frequency and amplitude in different applications, the issue of MR compatibility, actuation principles, design complexity, and scanner synchronization issues. The future challenges in this field are also described.