bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B
Authors: Morgan Ann W , Barrett Jennifer H , Griffiths Bridget , Subramanian Deepak , Robinson Jim I , Keyte Viki H , Ali Manir , Jones Elizabeth A , Old Robert W , Ponchel Frederique , Boylston Arthur W , Situnayake R Deva , Markham Alexander F , Emery Paul , Isaacs John D
Published: November 2005

The Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis.
Adalimumab clinical efficacy is associated with rheumatoid factor and anti-cyclic citrullinated peptide antibody titer reduction: a one-year prospective study
Authors: Atzeni Fabiola , Sarzi-Puttini Piercarlo , Dell' Acqua Donata , de Portu Simona , Cecchini Germana , Cruini Carola , Carrabba Mario , Meroni Pier Luigi
Published: November 2005

Studies on autoantibody production in patients treated with tumor necrosis factor-α (TNF-α) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-α antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-β2 glycoprotein I (anti-β2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-β2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-β2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.
HER-2 overexpression differentially alters transforming growth factor-β responses in luminal versus mesenchymal human breast cancer cells
Authors: Wilson Cindy A , Cajulis Elaina E , Green Jennifer L , Olsen Taylor M , Chung Young Ah , Damore Michael A , Dering Judy , Calzone Frank J , Slamon Dennis J
Published: November 2005

Introduction

Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-β) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland. Thus, to better understand the mechanisms by which HER-2 overexpression promotes the early stages of breast cancer, we directly assayed the cellular and molecular effects of TGF-β1 on breast cancer cells in the presence or absence of overexpressed HER-2.

Methods

Cell proliferation assays were used to determine the effect of TGF-β on the growth of breast cancer cells with normal or high level expression of HER-2. Affymetrix microarrays combined with Northern and western blot analysis were used to monitor the transcriptional responses to exogenous TGF-β1 in luminal and mesenchymal-like breast cancer cells. The activity of the core TGF-β signaling pathway was assessed using TGF-β1 binding assays, phospho-specific Smad antibodies, immunofluorescent staining of Smad and Smad DNA binding assays.

Results

We demonstrate that cells engineered to over-express HER-2 are resistant to the anti-proliferative effect of TGF-β1. HER-2 overexpression profoundly diminishes the transcriptional responses induced by TGF-β in the luminal MCF-7 breast cancer cell line and prevents target gene induction by a novel mechanism that does not involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c-myc repression. Conversely, HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-β induced pro-invasive and pro-metastatic gene signature.

Conclusion

HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-β. In contrast, HER-2 and TGF-β signaling pathways can cooperate to promote especially aggressive disease behavior in the context of a highly invasive breast tumor model.
Anti-L-selectin antibody therapy does not worsen the postseptic course in a baboon model
Authors: Redl Heinz R , Martin Ulrich , Khadem Anna , Pelinka Linda E , van Griensven Martijn
Published: November 2005

Introduction

Anti-adhesion molecule therapy prevents leukocytes from extravasating. During exaggerated inflammation, this effect is wanted; however, during infection, blocking diapedesis may be detrimental. In this study, therefore, the potential risks of anti-L-selectin antibody therapy were evaluated in a primate model of sepsis.

Methods

Sixteen baboons were anesthetized and randomized into two groups. The experimental group received 2 mg/kg of the anti-L-selectin antibody HuDREG-55 and the control group received Ringer's solution prior to the onset of a 2 h infusion of Escherichia coli (1–2 × 109 colony forming units (CFU)/kg body weight). Serial blood samples were drawn over a 72 h period for the measurement of tumour necrosis factor-α, IL-6 and polymorphonuclear elastase. In addition, blood gas analysis, hematology and routine clinical chemistry were determined to monitor cardiovascular status, tissue perfusion and organ function.

Results

The three-day mortality rate and the mean survival time after E. coli-induced sepsis were similar in the two groups. The bacterial blood CFU levels were significantly higher in the placebo group than in the anti-L-selectin group. Other parameters measured throughout the 72 h experimental period, including the cardiovascular, immunologic, and hematologic responses as well as indicators of organ function and tissue perfusion, were similar in the two groups, with the exception of serum creatinine and mean arterial pressure at 32 h after E. coli challenge.

Conclusion

Anti-L-selectin therapy did not adversely affect survival, promote organ dysfunction or result in major side effects in the baboon sepsis model. Additionally, as anti-L-selectin therapy improved the bacterial clearance rate, it appears that this therapy is not detrimental during sepsis. This is in contrast to previous studies using the baboon model, in which antibody therapy used to block CD18 increased mortality.
Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445]
Authors: Pearse Rupert , Dawson Deborah , Fawcett Jayne , Rhodes Andrew , Grounds R Michael , Bennett E David
Published: November 2005

Introduction

Goal-directed therapy (GDT) has been shown to improve outcome when commenced before surgery. This requires pre-operative admission to the intensive care unit (ICU). In cardiac surgery, GDT has proved effective when commenced after surgery. The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery.

Methods

This was a randomised controlled trial with concealed allocation. High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min-1 m-2 or to conventional management. Cardiac output was measured by lithium indicator dilution and pulse power analysis. Patients were followed up for 60 days.

Results

Sixty-two patients were randomised to GDT and 60 patients to control treatment. The GDT group received more intravenous colloid (1,907 SD ± 878 ml versus 1,204 SD ± 898 ml; p < 0.0001) and dopexamine (55 patients (89%) versus 1 patient (2%); p < 0.0001). Fewer GDT patients developed complications (27 patients (44%) versus 41 patients (68%); p = 0.003, relative risk 0.63; 95% confidence intervals 0.46 to 0.87). The number of complications per patient was also reduced (0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient; p = 0.002). The median duration of hospital stay in the GDT group was significantly reduced (11 days (IQR 7 to 15) versus 14 days (IQR 11 to 27); p = 0.001). There was no significant difference in mortality (seven patients (11.3%) versus nine patients (15%); p = 0.59).

Conclusion

Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay. The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission.
Changes in central venous saturation after major surgery, and association with outcome
Authors: Pearse Rupert , Dawson Deborah , Fawcett Jayne , Rhodes Andrew , Grounds R Michael , Bennett E David
Published: November 2005

Introduction

Despite recent interest in measurement of central venous oxygen saturation (ScvO2), there are no published data describing the pattern of ScvO2 changes after major general surgery or any relationship with outcome.

Methods

ScvO2 and other biochemical, physiological and demographic data were prospectively measured for 8 hours after major surgery. Complications and deaths occurring within 28 days of enrolment were included in the data analysis. Independent predictors of complications were identified with the use of logistic regression analysis. Optimum cutoffs for ScvO2 were identified by receiver operator characteristic analysis.

Results

Data from 118 patients was analysed; 123 morbidity episodes occurred in 64 these patients. There were 12 deaths (10.2%). The mean ± SD age was 66.8 ± 11.4 years. Twenty patients (17%) underwent emergency surgery and 77 patients (66%) were male. The mean ± SD P-POSSUM (Portsmouth Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity) score was 38.6 ± 7.7, with a predicted mortality of 16.7 ± 17.6%. After multivariate analysis, the lowest cardiac index value (odds ratio (OR) 0.58 (95% confidence intervals 0.37 to 0.9); p = 0.018), lowest ScvO2 value (OR 0.94 (0.89 to 0.98); p = 0.007) and P-POSSUM score (OR 1.09 (1.02 to 1.15); p = 0.008) were independently associated with post-operative complications. The optimal ScvO2 cutoff value for morbidity prediction was 64.4%. In the first hour after surgery, significant reductions in ScvO2 were observed, but there were no significant changes in CI or oxygen delivery index during the same period.

Conclusion

Significant fluctuations in ScvO2 occur in the immediate post-operative period. These fluctuations are not always associated with changes in oxygen delivery, suggesting that oxygen consumption is also an important determinant of ScvO2. Reductions in ScvO2 are independently associated with post-operative complications.
Tbx1expression in pharyngeal epithelia is necessary for pharyngeal arch artery development
Authors: Zhang Zhen , Cerrato Fabiana , Xu Huansheng , Vitelli Francesca , Morishima Masae , Vincentz Joshua , Furuta Yasuhide , Ma Lijiang , Martin James F. , Baldini Antonio , Lindsay Elizabeth
Published: November 2005

During embryonic life, the initially paired pharyngeal arch arteries (PAAs)follow a precisely orchestrated program of persistence and regression that leads to the formation of the mature aortic arch and great vessels. When this program fails, specific cardiovascular defects arise that may be life threatening or mild, according to the identity of the affected artery. Fourth PAA-derived cardiovascular defects occur commonly in DiGeorge syndrome and velocardiofacial syndrome (22q11DS), and in Tbx1+/–mice that model the 22q11DS cardiovascular phenotype. Tbx1 is expressed in pharyngeal mesoderm, endoderm and ectoderm, and, in addition, we show that it is expressed in precursors of the endothelial cells that line the PAAs, thus expanding the number of tissues in which Tbx1 is potentially required for fourth PAA development. In this study, we have used cell fate mapping and tissue-specific gene deletion, driven by six different Cre lines,to explore Tbx1 gene-dosage requirements in the embryonic pharynx for fourth PAA development. Through this approach, we have resolved the spatial requirements for Tbx1 in this process, and we show pharyngeal epithelia to be a critical tissue. We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous.
Evolutionarily conserved domains required for activation and repression functions of the Drosophila Hox protein Ultrabithorax
Authors: Tour Ella , Hittinger Chris Todd , McGinnis William
Published: November 2005

While testing the functions of deletion mutants in the Hox protein Ultrabithorax (Ubx), we found that the embryonic repression function of Ubx on Distal-less transcription in limb primordia is highly concentration dependent. The steep sigmoidal relationship between in vivo Ubx concentration and Distal-less repression is dependent on the Ubx YPWM motif. This suggests that Ubx cooperatively assembles a multi-protein repression complex on Distal-less regulatory DNA with the YPWM motif as a key protein-protein interface in this complex. Our deletion mutants also provide evidence for a transcriptional activation domain in the N-terminal 19 amino acids of Ubx. This proposed activation domain contains a variant of the SSYF motif that is found at the N termini of many Hox proteins, and is conserved in the activation domain of another Hox protein, Sex combs reduced. These results suggest that the N-terminal region containing the SSYF motif has been conserved in many Hox proteins for its role in transcriptional activation.
Zebrafishvps33b, an ortholog of the gene responsible for human arthrogryposis-renal dysfunction-cholestasis syndrome, regulates biliary development downstream of the onecut transcription factorhnf6
Authors: Matthews Randolph P. , Plumb-Rudewiez Nicolas , Lorent Kristin , Gissen Paul , Johnson Colin A. , Lemaigre Frederic , Pack Michael
Published: November 2005

Arthrogryposis-renal dysfunction-cholestasis syndrome (ARC) is a rare cause of cholestasis in infants. Causative mutations in VPS33B, a gene that encodes a Class C vacuolar sorting protein, have recently been reported in individuals with ARC. We have identified a zebrafish vps33b-ortholog that is expressed in developing liver and intestine. Knockdown of vps33b causes bile duct paucity and impairs intestinal lipid absorption, thus phenocopying digestive defects characteristic of ARC. By contrast, neither motor axon nor kidney epithelial defects typically seen in ARC could be identified in vps33b-deficient larvae. Biliary defects in vps33b-deficient zebrafish larvae closely resemble the bile duct paucity associated with knockdown of the onecut transcription factor hnf6. Consistent with this, reduced vps33b expression was evident in hnf6-deficient larvae and in larvae with mutation of vhnf1, a downstream target of hnf6. Zebrafish vhnf1, but not hnf6, increases vps33b expression in zebrafish embryos and in mammalian liver cells. Electrophoretic mobility shift assays suggest that this regulation occurs through direct binding of vHnf1 to the vps33b promoter. These findings identify vps33b as a novel downstream target gene of the hnf6/vhnf1 pathway that regulates bile duct development in zebrafish. Furthermore, they show that tissue-specific roles for genes that regulate trafficking of intracellular proteins have been modified during vertebrate evolution.
The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature
Authors: Wilm Bettina , Ipenberg Annemieke , Hastie Nicholas D. , Burch John B. E. , Bader David M.
Published: November 2005

Most internal organs are situated in a coelomic cavity and are covered by a mesothelium. During heart development, epicardial cells (a mesothelium) move to and over the heart, undergo epithelial-mesenchymal transition (EMT), and subsequently differentiate into endothelial and vascular smooth muscle cells. This is thought to be a unique process in blood vessel formation. Still,structural and developmental similarities between the heart and gut led us to test the hypothesis that a conserved or related mechanism may regulate blood vessel development to the gut, which, similar to the heart, is housed in a coelomic cavity. By using a combination of molecular genetics, vital dye fate mapping, organ culture and immunohistochemistry, we demonstrate that the serosal mesothelium is the major source of vasculogenic cells in developing mouse gut. Our studies show that the gut is initially devoid of a mesothelium but that serosal mesothelial cells expressing the Wilm's tumor protein (Wt1)move to and over the gut. Subsequently, a subset of these cells undergoes EMT and migrates throughout the gut. Using Wt1-Cre genetic lineage marking of serosal cells and their progeny, we demonstrate that these cells differentiate to smooth muscle of all major blood vessels in the mesenteries and gut. Our data reveal a conserved mechanism in blood vessel formation to coelomic organs, and have major implications for our understanding of vertebrate organogenesis and vascular deficiencies of the gut.
Normal myoblast fusion requires myoferlin
Authors: Doherty Katherine R. , Cave Andrew , Davis Dawn Belt , Delmonte Anthony J. , Posey Avery , Earley Judy U. , Hadhazy Michele , McNally Elizabeth M.
Published: November 2005

Muscle growth occurs during embryonic development and continues in adult life as regeneration. During embryonic muscle growth and regeneration in mature muscle, singly nucleated myoblasts fuse to each other to form myotubes. In muscle growth, singly nucleated myoblasts can also fuse to existing large,syncytial myofibers as a mechanism of increasing muscle mass without increasing myofiber number. Myoblast fusion requires the alignment and fusion of two apposed lipid bilayers. The repair of muscle plasma membrane disruptions also relies on the fusion of two apposed lipid bilayers. The protein dysferlin, the product of the Limb Girdle Muscular Dystrophy type 2 locus, has been shown to be necessary for efficient, calcium-sensitive,membrane resealing. We now show that the related protein myoferlin is highly expressed in myoblasts undergoing fusion, and is expressed at the site of myoblasts fusing to myotubes. Like dysferlin, we found that myoferlin binds phospholipids in a calcium-sensitive manner that requires the first C2A domain. We generated mice with a null allele of myoferlin. Myoferlin null myoblasts undergo initial fusion events, but they form large myotubes less efficiently in vitro, consistent with a defect in a later stage of myogenesis. In vivo, myoferlin null mice have smaller muscles than controls do, and myoferlin null muscle lacks large diameter myofibers. Additionally, myoferlin null muscle does not regenerate as well as wild-type muscle does, and instead displays a dystrophic phenotype. These data support a role for myoferlin in the maturation of myotubes and the formation of large myotubes that arise from the fusion of myoblasts to multinucleate myotubes.
Root cause identification and physics of impact-induced driveline noise in vehicular powertrain systems
Authors: Theodossiades S , Gnanakumarr M , Rahnejat H
Published: November 2005

Numerical and experimental investigations shed light on the root causes leading to the emergence and persistence of an acute metallic noise in rear wheel drive light truck drivelines. Sudden demands in engine output torque combined with the presence of lash zones give rise to a phenomenon that is onomatopoeically referred to as clonk. Its multi physics nature requires a comprehensive study, which includes rigid multi-body dynamics, flexible body oscillations, and noise radiation computation. The verification of numerical results is achieved through the design and implementation of a transient dynamic experimental rig, which comprises the complete drivetrain from the engine flywheel to the rear axle. Parametric studies reveal high-frequency contributions in the driveline vibration response of certain structural modes of the driveshaft pieces, which are induced by remote impact of meshing transmission teeth through backlash. The numerically predicted spectrum of vibration is in good qualitative agreement with the experimental measurements. Combined study of the aforementioned results reveals the components that amplify the clonk noise.
A study of the human ability to detect road surface type on the basis of steering wheel vibration feedback
Authors: Giacomin J , Woo Y J
Published: November 2005

A study was performed to investigate the human ability to detect road surface type on the basis of the associated steering wheel vibration feedback. Tangential direction acceleration time histories measured during road testing of a single mid-sized European automobile were used as the basis for the study. Scaled and frequency-filtered copies of two base stimuli were presented to test subjects in a laboratory setting during two experiments that each involved 25 participants. Theory of signal detection (TSD) was adopted as the analytical framework, and the results were summarized by means of the detectability index d' and as receiver operating curve (ROC) points. The results of the experiment to investigate the effect of scaling suggested monotonic relationships between stimulus level and detection for both road surfaces. Detection of the tarmac surface improved with reductions in acceleration level, while the opposite was true of the cobblestone surface. The ROC points for both surfaces were characterized by gradual increases in detectability as a function of acceleration level, obtaining hit rates of nearly 100 per cent at optimum. The results of the experiment to investigate the effect of frequency bandwidth suggested a monotonically increasing relationship between detectability and the bandwidth of the vibration stimuli. Detection of both road surfaces improved with increases in bandwidth. Average hit rates exceeded 80 per cent for stimuli covering the frequency range from 0 to 80 Hz. Human detection of road surface type appears to depend on the long-term memory model, or cognitive interpretation mechanism, associated with each surface. The complexity of the measured response suggests the need to categorize and classify incoming data before an optimal choice of feedback stimuli can be made in automotive steering systems.
Control of a variable-geometry turbocharged and wastegated diesel engine
Authors: Rajamani R
Published: November 2005

This paper addresses the problem of controlling a turbocharged diesel engine so as to minimize NOx and smoke emissions while ensuring that the driver's torque demands are met. A diesel engine equipped with a variable-geometry turbocharger (VGT) and an exhaust gas recirculation (EGR) valve is considered. The technical challenges in the control design task include the multivariable non-linear dynamics of the system and the unavailability of key states for feedback. A control strategy based on non-linear control synthesis is developed and shown accurately to control the air-fuel ratio (AFR) and the burned gas fraction in the intake manifold, F1, to desired values in the presence of changing operating conditions. The variables F1 and AFR are shown to be crucial for feedback. Since neither of these variables can be measured, an observer based on flow and pressure sensor measurements is developed for their real-time estimation. Lyapunov theory is used to show that the developed observer is asymptotically stable. Simulation results confirm the performance of the observer and the observer-based feedback controller. The importance of the developed observer extends beyond the application discussed in this paper. It could be useful for a wide variety of different control and diagnostic applications in diesel engines.
Hoop stresses in the con-rod small end
Authors: Strozzi A , De Bona F
Published: November 2005

Having in mind con-rods for motorbike and car engines, and spurred by the disagreements evidenced in the pertinent literature, the maximum circumferential stresses within the small end are investigated analytically, photoelastically, and numerically. The analytical models are based upon a plane assumption, and they adopt both beam and theory of elasticity idealizations. The plane photoelastic study concentrates on small ends with outer to inner radii ratios ranging from 1.2 to 1.5. A plane numerical model aimed at thoroughly mimicking the pin ovalization is developed, and a design chart of the peak hoop stress within the small end is provided for a wide spectrum of small end and pin geometries, for zero initial clearance. Such diagrams allow a prompt preliminary dimensioning of the small end to be carried out, which may be refined by effecting a three-dimensional finite element study of the specific con-rod geometry. The consequences of an initial clearance between small end bore and gudgeon pin are examined for selected geometries, and three-dimensional aspects are explored for specific con-rod shapes.
Simulated behaviour of a vehicle with V-belt geared neutral transmission with variator slip control
Authors: Veenhuizen P A , Bonsen B , Klaassen T W G L , van de Meerakker K G O , Nijmeijer H , Veldpaus F E
Published: November 2005

Combining both launch and reverse drive functions with the ratio change function in a geared neutral continuously variable transmission (GN-CVT), thus making a launch device like a torque converter and a drive-neutral-reverse (DNR) set obsolete, is attracting considerable attention. This paper covers the modelling and simulation of a V-belt geared neutral transmission in and around the geared neutral point. Owing to the specific nature of the geared neutral state, conventional driveline simulation models are shown to be inadequate. Experimental results are presented, allowing a more detailed description of the functional properties of the V-belt variator, especially those related to small amounts of slip between the belt and the pulleys. The measured data will be analysed to obtain grey model fitting parameters, which allow the data to be used in a simulation program based on a dynamic driveline model. It will be shown that, with a GN-CVT, stall and launch performance can be considerably better than that achieved with a driveline with a torque converter (TC).
Fuzzy logic controller applied to a variable geometry turbine turbocharger
Authors: Dambrosio L , Pascazio G , Fortunato B
Published: November 2005

This paper provides an adaptive technique for the control of a variable geometry turbine (VGT) in a turbocharged compression ignition engine. The adaptive control is based on a fuzzy logic control scheme and a least-squares parameter estimator algorithm. In order to test the performance of the proposed control technique, a numerical model of the engine has been used, which employs a thermodynamic (zero-dimensional) approach. The paper will show that the fuzzy logic control technique is able to take into account the non-linearity of the controlled system and to reject white noise affecting the measurement chain.
Functional approximation-based adaptive sliding control with fuzzy compensation for an active suspension system
Authors: Chen Hung-Yi , Huang Shiuh-Jer
Published: November 2005

Since it is difficult to establish an accurate dynamic model of a physical active suspension system for a model-based control design, various model-free approaches have been introduced in this field of application. This paper proposes a functional approximation-based adaptive sliding controller with fuzzy compensation for a quarter-car active suspension system. The functional approximation technique is employed to represent the unknown function and release the model-based requirement of a sliding mode control. In addition, a self-tuning fuzzy scheme is introduced to compensate the model approximation error for improving the control performance. The update laws for the coefficients of the Fourier series functions and the fuzzy tuning parameters can be derived from the Lyapunov function directly for guaranteeing the system stability. The simulation results show that the proposed control approach can suppress effectively the vibration amplitude of this suspension system under severe external uncertainties. The dynamic performance of this proposed controller is compared with that of the adaptive sliding controller without fuzzy compensation to show the performance improvement of the inducing of fuzzy control loop.
The cam profile switching state detection method
Authors: Stotsky A
Published: November 2005

A new method for the detection of the CPS (cam profile switching) state of spark ignition automotive engines is proposed and implemented. The method is based on the evaluation of the amplitude and the phase of the component of the intake manifold pressure signal with the period of 720 CA (crank angle) degrees. The method permits the detection of the CPS bank failure even at high rotational speeds.
Quality function deployment and its application to automotive door design
Authors: Miller K , Brand C , Heathcote N , Rutter B
Published: November 2005

In order to be competitive, automotive design is now focusing on optimizing perceived qualities in terms of sound and operational efforts. Phases 1 and 2 of the four-phase quality function deployment (QFD) process have been applied to family segment vehicle side doors. The objective was to optimize customer comfort when opening and closing the door. This paper documents the QFD and discusses the reasoning used, assumptions made, and conclusions drawn. A customer clinic was used to capture the voice of the customer. A ranking method, morphological chart, and controlled convergence matrix are used to organize data. The door design obtained incorporates simple observations and electrical technology that could significantly reduce the effort required in opening and closing the vehicle door.
Estimation of engine rotational dynamics using a closed-loop estimator with stroke identification for engine management systems
Authors: Chen B-C , Wu Y-Y , Hsieh F-C
Published: November 2005

In order to study the effect of the crank sensor noise on the engine management system (EMS), an algorithm using a closed-loop estimator with stroke identification is proposed to estimate the engine rotational dynamics. Estimated crank angle and engine speed are used for fuel injection and ignition control systems. The closed-loop estimator design is based on a linear model by assuming that the engine rotational inertia is constant. Since the effective inertia actually varies with different crank angles, the stability of the proposed algorithm is assessed using the Lyapunov stability theorem. Performances of the proposed and traditional algorithms are evaluated using a non-linear engine model with a four-plus-one-tooth crankshaft wheel in Matlab/Simulink. The estimated crank angle and engine speed of the traditional algorithm can be significantly affected by large sensor noises resulting from the poorly grounded ignition coil. It was found that the proposed algorithm can mitigate the noise impact and thus maintain the desired engine control performance.
Method for estimating tyre cornering stiffness from basic tyre information
Authors: Hewson P
Published: November 2005

This paper proposes a simple mathematical tyre model that estimates tyre cornering stiffness. The model is derived by considering the tyre to be a combination of two independent systems. The sidewalls are assumed to be negligibly stiff in the lateral direction, and hence their influence on the lateral dynamics of the tyre will be ignored. The belt and tread area of the tyre will be considered to be an homogeneous uniform band, and its stiffness will be estimated with reference to measured tyre data. The resulting model is estimated to yield cornering stiffness values within about 30 per cent of the actual measured values.
A new approach to the design of a speed-torque-controlled rubber V-belt variator
Authors: Cammalleri M
Published: November 2005

This paper presents a new model for a torque-speed-sensing rubber V-belt variator. The actuators are of the centrifugal roller kind on the driver side and a helical torque cam plus a compression-torsion spring on the driven side. The equations permit designing the actuator geometry in order to keep the transmissible torque as close as possible to the torque request in the whole operative field.

Moreover, a procedure is suggested for the most proper design of an automatic variator of this kind. It permits choosing the required variogram of the transmission, i.e. the matching between the engine and the transmission, and designing the actuators: roller mass, housing shape, contact plate angle for the centrifugal roller actuator, and helical guide slope for the torque cam actuator. Furthermore, the degree of engine transmission matching can be calculated at part load for fixed actuators.

Extensive experimental tests were carried out on a proper bench test to validate the procedure.
Energy requirement assessment on an electrically heated catalyst with heat-storing material of a small four-stroke engine during cold start
Authors: Horng R-F , Wu T-S
Published: November 2005

An electrically heated catalyst (EHC) with heat-storing material of a four-stroke motorcycle engine operating from cold-start conditions was studied to investigate the effect of input energy on the conversion characteristics of the catalyst from cold start. The parameters investigated were the length of the heat-storing material, the heating temperature, the CO setting level, and the heating position. The heating temperatures were 100, 140, 180, and 220 °C and the CO setting levels were 1.3 and 1.8 per cent. The heating positions were at the inlet and mid-section of the catalyst. The heat-storing material was made of stainless steel and was 15 mm wide and 0.3 mm thick. The two lengths tested were 30 and 60 cm. The experimental results showed that good conversion efficiency was attained, even with a low heating energy, using the shorter heat-storing material coupled with a high CO setting. In contrast, good conversion efficiency was not attained with a low heating energy using the longer heat-storing material. Furthermore, heating at the inlet of the catalyst resulted in better CO conversion efficiency with the combination of shorter heat-storing material and higher CO setting. A good CO conversion was also obtained when heating at the mid-section of the catalyst with the combination of longer heat-storing material and higher CO setting. Analysis of the CO converted mass per unit total input energy showed that a peak value generally occurred at a heating temperature of either 140 or 180 °C.
Recurrent bacterial vaginosis: the use of maintenance acidic vaginal gel following treatment
Authors: Wilson J D , Shann S M , Brady S K , Mammen-Tobin A G , Evans A L , Lee R A
Published: November 2005

Bacterial vaginosis (BV) frequently recurs after treatment. One option in the management of recurrences is to keep the vaginal pH at 4.5 or less, in order to prevent overgrowth of bacteria, until the normal lactobacilli are re-established. We report the outcome of using maintenance acetic acid vaginal gel, after treatment of BV, in a sample of 49 women with frequent recurrences. Half of the women had no further recurrences, and in those who did there was a significant increase in time to first recurrence (4.8 months) after commencing the gel compared with the previous recurrence (2.1 months). Prior to using acidic gel, the mean recurrence rate in 49 women was 4.4 per woman/year, and this was reduced to 0.6 recurrences per woman/year. As there are few effective therapies for women with recurrent BV, we feel this offers an option that can currently be used in clinical practice.
The feasibility of voluntary counselling and HIV testing for pregnant women using community volunteers in Zimbabwe
Authors: Shetty Avinash K , Mhazo Miriam , Moyo Sostain , von Lieven Andrea , Mateta Patrick , Katzenstein David A , Maldonado Yvonne , Hill David , Bassett Mary T
Published: November 2005

The purpose of this pilot project was to assess the feasibility and acceptability of voluntary counselling and HIV testing (VCT) by pregnant women using community volunteers in Zimbabwe to prevent mother to child transmission (MTCT) of HIV. From July 1999 to June 2001, a short-course zidovudine (ZDV)-based perinatal HIV prevention programme was initiated in two antenatal clinics. Community volunteers, recruited from local community organizations, underwent a two-week training course in VCT, which included HIV/AIDS facts, systematic counselling approach, and practical counselling techniques using scripts and role-play. Rapid HIV testing was performed after informed consent. Lay counsellors conducted individual pre- and post-test counselling for HIV. A total of 35 women community volunteers were trained in VCT; 34 graduated and committed to work four hours per week in the clinic. Of the 6051 pregnant women presenting for antenatal clinics (ANC), 1824 (30%) underwent pre-test counselling and 1547 (26%) were tested, and 429 (28%) were HIV infected. Overall, 1283 (83%) returned for their test results including 406 (95%) of HIV-infected women. Of the 406 HIV-infected women who collected their test results, only 203 (50%) opted for ZDV prophylaxis to prevent MTCT of HIV. Over the two-year study period, two counsellors died and three sought employment at other organizations. Adherence to duty roster was 97% and no breach of confidentiality was reported. Despite many challenges, VCT delivered by community volunteers is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their infants. This programme is being implemented at several urban and rural MTCT sites in Zimbabwe and can serve as a model for other resource-poor countries.
Hepatitis C virus infection, HIV co-infection, and associated risk among injecting drug users in Togliatti, Russia
Authors: Rhodes Tim , Platt Lucy , Judd Ali , Mikhailova Larissa Albertovna , Sarang Anya , Wallis Nigel , Alpatova Tatiana , Hickman Matthew , Parry John V
Published: November 2005

The objective of this study was to estimate the prevalence of hepatitis C virus (HCV) infection and co-infection with HIV among injecting drug users (IDUs) in Togliatti City, Russia. Unlinked anonymous cross-sectional survey of IDUs recruited from community settings, with oral fluid sample collection for HCV and HIV antibody (anti-HCV, anti-HIV) testing, was carried out. The anti-HCV prevalence was 87% (357/411), anti-HIV prevalence 56% (234/418), and 93% (214/230) of HIV-positive IDUs were co-infected with HCV. Only 23% (94/411) of those HCV positive self-reported as such. In an adjusted model, increased odds of HCV positivity were associated with needle and syringe, as well as injecting paraphernalia sharing in the last four weeks. IDUs injecting more than once with the same needle also had raised odds. There were no marked associations between HCV positivity and the duration of injecting or age group. Almost all IDUs were HCV positive, and almost all HIV-positive IDUs were HCV co-infected. There is an urgent need to maximize syringe distribution coverage, develop health promotion targeting HCV prevention for IDUs, and improve access among IDUs to treatments for HIV and HCV infection.
Management of recurrent genital herpes: a survey of UK genitourinary medicine clinics in 2003
Authors: Hamill M , Goldmeier D
Published: November 2005

We carried out a survey of all UK genitourinary (GU) medicine clinics, via postal questionnaire, in order to evaluate the current management of recurrent genital herpes (RGH) in the GU medicine setting. Respondents were invited to answer questions regarding various aspects of herpes simplex virus (HSV) management. There was a 62% response rate. Analysis of the returned surveys revealed that the vast majority of clinics (96%) provided drug treatment for RGH, with 81% having a clinic policy for the management of genital herpes (GH). A majority (64%) of clinics had access to some type of counselling or psychological therapy and 47% encouraged collaboration with primary care for follow-up prescribing. Of the clinics providing drug therapy for RGH, 80% used aciclovir alone with smaller numbers having access to aciclovir, famciclovir and valaciclovir. While many clinics are meeting the British Association of Sexual Health and HIV (BASHH) guidelines, improvements can be made to increase the availability of psychological support to patients with HSV and improve links with primary care.
Self-sampling versus physician-sampling for human papillomavirus testing
Authors: Agorastos T , Dinas K , Lloveras B , Font R , Kornegay JR , Bontis J , de Sanjose S
Published: November 2005

We evaluated the detection of human papillomavirus (HPV) infection using two sampling methods of cervical exfoliated cells, consisting of self-sampling of vaginal cells and cervical sampling performed by the physician. Women included were 379 patients of the general population attending outpatient clinics in Northern Greece for routine cytological cervical dysplasia screening. HPV DNA detection was similar with both sampling techniques. The HPV prevalences in self-collected samples were 4.7% and 3.7% in the physician-collected samples ( P>0.05). The Kappa statistic for HPV DNA agreement between the two methods was 0.54 (95% Confidence interval = 0.33–0.75). Self-sampling of cervico-vaginal exfoliated cells could be used as an alternative option to test for HPV infection.
A review on pelvic inflammatory disease
Authors: Barrett S , Taylor C
Published: November 2005

Pelvic inflammatory disease (PID) remains a significant cause of morbidity worldwide, with the potential to result in serious reproductive complications. Much of the definitive work regarding PID was completed in the 1960s and 1970s. More recently, however, there have been a range of studies published that have contributed to our understanding of PID. Aetiologically, the main pathogens are chlamydia and gonorrhoea, but may include Mycoplasma genitalium and anaerobic Gram-negative rods. Risk factors associated with the development of PID include inconsistent barrier contraception, possibly vaginal douching, and the oral contraceptive pill likely masking the clinical severity of the disease. The small risk associated with the intrauterine device is limited to the first few weeks after insertion. New diagnostic techniques being evaluated include Doppler ultrasound and magnetic resonance imaging. Management must be prompt to prevent complications, and there are no apparent differences in clinical outcomes, whether treated as an inpatient or outpatient. Effective disease prevention includes widespread chlamydia screening and improving education.
Chronic herpes simplex virus type-2 infection and HIV viral load
Authors: Duffus W A , Mermin J , Bunnell R , Byers R H , Odongo G , Ekwaru P , Downing R
Published: November 2005

By December 2003, the estimated adult HIV/AIDS prevalence rate in sub-Saharan Africa was 7.5–8.5%, and rates of herpes simplex virus type-2 (HSV-2) infection among adults aged >30 years ranged from 60% to 82%. However, little is known about the natural history of HIV/HSV-2 co-infection in this population. We evaluated HIV viral load and CD4+ cell counts among persons with and without chronic HSV-2 co-infection in a cross-sectional study of HIV-infected persons not receiving antiretroviral therapy. HSV-2 and HIV co-infection was associated with a 0.3 log copies/mL higher HIV viral load compared with persons without HSV-2 infection ( P=0.014). Chronic HSV-2 infection may have a negative effect on the clinical course of persons with HIV.
Research Commentary: The Next Wave of Nomadic Computing
Authors: Lyytinen Kalle , Yoo Youngjin
Published: November 2005

A nomadic information environment is a heterogeneous assemblage of interconnected technological, and social, and organizational elements that enable the physical and social mobility of computing and communication services between organizational actors both within and across organizational borders. We analyze such environments based on their prevalent features of mobility, digital convergence, and mass scale, along with their mutual interdependencies. By using a framework that organizes research topics in nomadic information environments at the individual, team, organizational, and inter organizational levels and is comprised of both service and infrastructure development, we assess the opportunities and challenges for IS research. These deal with the design, use, adoption, and impacts of nomadic information environments. We conclude by discussing research challenges posed by nomadic information environments for information systems research skills and methods. These deal with the need to invent novel research methods and shift our research focus, the necessity to question the divide between the technical and the social, and the need to better integrate developmental and behavioral (empirical) research modes.