bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Analysis of Piston-Ring Wear and Oil Consumption for an Internal Combustion Engine
Authors: Chui Boon-Keat , Schock Harold J.
Published: January 2009

This paper presents the computational analysis of piston ring wear and oil consumption for an internal combustion (IC) engine. Two computational models, piston-ring wear and oil consumption, are employed to simulate the results for this analysis. Both instantaneous and transient results are discussed. The piston-ring wear model, namely WEAR, is built on the fundamentals of mechanical and adhesive wear mechanism; while the oil consumption, namely OILCONSUME, is on the fundamentals of oil vaporization and upper-ring gap oil reverse flow mechanisms. The two models are integrated with two external engine simulators: the Ford Motor Company General Engine SIMulation (GESIM) of the Ford Motor Company, and the Cylinder kit Analysis System for Engines (CASE) of the Michigan State University Engine Research Laboratory. An objective of this analysis is to understand how the engine operation condition impacts the piston-ring wear and the oil consumption per engine cycle basis. Also, it is to understand how the piston-ring wear affects the oil consumption and other engine mechanisms on a long time basis. A virtual Ford 4.6L-V8 engine has been tested on various engine speeds and loads to produce the computational results. The results show that the engine load and the engine speed play significant roles, individually and collectively, on the engine performance. The results also show the dependence of the oil consumption and the blow-by on the piston-ring wear over long-time engine run. The instantaneous and transient simulations have provided useful insights on the relation between the piston-ring wear and the oil consumption mechanisms in an IC engine.
Effect of EGR on Heavy-Duty Diesel Engine Emissions Characterized With Laser-Induced Incandescence
Authors: Neill W. Stuart , Smallwood Gregory J. , Snelling David R. , Sawchuk Robert A. , Clavel Dan , Gareau Daniel , Chippior Wallace L.
Published: January 2009

The regulations governing diesel engine particulate matter (PM) and oxides of nitrogen (NOx) emissions are becoming increasingly stringent. New instrumentation is urgently needed to make accurate and precise measurements of PM emissions from low-emitting engines and emission control systems in a reasonable amount of time. Laser-induced incandescence (LII) is a technique for making temporally resolved measurements of soot volume fraction. LII offers real-time particulate concentration measurements over several orders of magnitude, and adds desirable information about particulate size and surface area. In this study, the exhaust gas recirculation (EGR) system of a heavy-duty diesel engine was tuned at eight speed/load conditions using quantitative LII. Soot concentrations measured by LII correlated strongly with measurements taken using the standard gravimetric technique and an AVL smoke meter.
Numerical Study to Achieve Stratified EGR in Engines
Authors: Ramadan Bassem H. , Gray Charles L. , Schock Harold J. , Hamady Fakhri J. , Hellman Karl H.
Published: January 2009

Exhaust Gas Re-circulation (EGR) has been used in intemal combustion engines to control automotive emissions. EGR is usually used to dilute the inlet charge, which consists of air, by redirecting part of the exhaust into the inlet manifold of the engine. This results in a reduction of the oxygen mass fraction in the inlet charge. However, dilution of the air-fuel mixture in an engine using stratified EGR could offer significant fuel economy saving comparable to lean burn or stratified charge direct-injection SI engines. The most critical challenge is to keep the EGR and air-fuel mixture separated, or to minimize the mixing between the two zones to an acceptable level for stable and complete combustion. Swirl-type stratified EGR and fuel-air flow structure is considered desirable for this purpose, because the circular shape of the cylinder tends to preserve the swirl motion. Moreover, the axial piston motion has minimal effect on the swirling motion of the fluid in the cylinder. In this study, we consider intake system design in order to generate a two-zone combustion system, where EGR is maintained in a layer on the periphery of the cylinder, and the fuel-air mixture is maintained in the center of the cylinder. KIVA-3V was used to perform numerical simulations on different EGR systems. The simulations were performed to determine if the two-zones can be generated in the cylinder, and to what extent mixing between the two zones occurs. For the engine geometries considered in this study, the results showed that it is possible to generate the two zones, but mixing is difficult to control.
On-Board Indicated Pressure and Torque Estimation in Engines With a High Number of Cylinders
Authors: Corti Enrico , Moro Davide
Published: January 2009

In recent years engine control development focused the attention on torque-based models, that allow improving driveability and implementing traction control strategies. The design of such a torque-based engine control strategy requires the knowledge of the torque produce by the engine, which depends on fuel injection time, spark advance, throttle opening, EGR command, … In the actual engine control strategies this is mainly done by means of static maps stored in the ECU memory. The real engine torque production under every operating condition can be evaluated by means of the in-cylinder pressure estimation, thus allowing a torque based closed loop control strategy. Many approaches are present in the literature showing the possibility of on-board estimating the actual torque produced by the engine not simply by using static maps, but estimating it through other measured signals. Most of the methodologies that do not require a specific sensor placed on the engine are based either on the engine speed fluctuations (measured by a pick-up facing the flywheel teeth) or on the engine block vibrations (measured by the knock sensor), performing better for engines with a low number of cylinders. The paper presents an original methodology based on the instantaneous engine speed fluctuations, that has been usefully applied to engines with higher number of cylinders. The methodology is based on the observation of the speed fluctuations in a crankshaft window inside the expansion stroke and on the hypothesis that there exists a strong correlation between these engine speed fluctuations and pressure inside the selected cylinder. This relationship has been characterized using Frequency Response Functions (FRF) for each steady-state engine operating condition. In the following the FRFs have been used to perform in-cylinder pressure and then indicated torque estimation under every operating condition, and a specific signal processing algorithm has been developed in order to apply the procedure during speed and load engine transients. The experimental tests have been conducted mounting a six-cylinder turbo-charged spark-ignited engine in a test cell. The application on-board a vehicle of the same methodology seems to be feasible due to the quickness of the algorithm employed and the presence on-board of all the sensors required for the implementation.
Measurement of Exhaust Gas Temperatures: Theoretical and Experimental Analysis
Authors: Cavina Nicolo`
Published: January 2009

The optimal management of the three-way catalytic converter is today widely recognized as one of the means to further reduce Spark Ignition (SI) engine polluting emissions, and therefore to respect future emission regulations. Its conversion efficiency is strictly dependent on the operating temperature, and most engine control strategies are today either based on mathematical models that determine such temperature as a function of the engine operating conditions, or on its direct measurement. It is therefore useful to investigate the errors that could arise when measuring exhaust gas temperatures, either during model identification tests or on board the vehicle. The paper presents a theoretical and experimental analysis on the phenomena that could lead to relevant measurement errors in such applications. A physical model of the heat transfer phenomena that take place in the exhaust manifold has been developed to estimate both the exhaust gas temperatures and the error that would arise while measuring them with typical sensors such as thermocouples. The exhaust manifold of a 1.2 liter SI engine was equipped with different types of sensors for the model identification and validation phases.
Investigation of Injection Pressure Effects on Medium Speed Diesel Engine Emissions
Authors: Glenn W. Doug , Gallagher Shawn M. , Primus Roy J. , Tamma Bhaskar
Published: January 2009

As with most internal combustion engines, the locomotive diesel is subjected to increasingly stringent regulatory emissions standards. Currently, diesel electric freight locomotives are regulated by the Tier 1 emission standards that went into effect January 1, 2002 as ruled by the United States Environmental Protection Agency (EPA). Beginning January 1, 2005 the US EPA Tier 2 diesel locomotive emissions standards will become effective. To achieve the new emissions standards an extensive engine development program was initiated. This paper will present a portion of the development conducted on a single cylinder engine (SCE) investigating the effects of injection pressure on emissions. The experimental results are presented with a discussion of the possible mechanisms leading to the results with supporting evidence from existing literature and analysis. This paper will focus on the effect of injection pressure as generated by pump capacity and nozzle cup hydraulic flow.
Modeling High-Pressure Spray Impingement
Authors: Rotondi Rossella , Arrighetti Cinzio
Published: January 2009

Numerical investigation of the spray-wall interaction was carried out. Wall interaction models that predict the post-impingement state of drops hitting a wall, under internal combustion engines conditions, are still missing. In this paper different existing models were implemented in a modified version of the KIVA3V code. Simulations concerning high pressure sprays in a chamber at different ambient pressures were made. Numerical radial penetrations and spray pattern were compared to experimental data.
Integration of System and Detailed CFD Models for IC Engine Applications
Authors: Gokhale Manoj , Tamma Bhaskar , Primus Roy J.
Published: January 2009

Stringent IC engine tailpipe emission regulations are being enforced worldwide. To meet the emission norms various emission reduction strategies are explored in conjunction with the fuel consumption improvements. To achieve these goals, modeling of engine system for combustion and emission plays a major role in minimizing the development cost and time. The successful application of combustion and emission modeling depends on the response, accuracy and run-time of the models being used. System level models are generally used to study and optimize the full IC engine system. These models have low runtime (2–10 mins) but are limited in their ability to describe and respond to the geometry and physics of complex fluid dynamics, combustion and emissions. Detailed CFD models are used for these areas but have long runtimes (8–40 hours). The procedure for developing and calibrating commercially available system and in-cylinder CFD software models are explained. Also the integration of these models to minimize the overall runtimes is described in detail.
Genetic Algorithms for the Vibroacoustic Optimization of the Thin Parts of I.C. Engine
Authors: Deng Xiaolong , Zhang Zongjie , Sun Chunpeng , Li Shaohe
Published: January 2009

The Noise Vibration Harshness (NVH) behavior of engines is one of the predominant factors for market acceptance of vehicles. To reach this goal it is necessary to reduce the absolute noise level and also the noise level in specific frequency ranges. The design of radiating structures for minimal sound radiation is a multidisciplinary problem that involves complex objective functions and expensive computations. In this paper, genetic algorithm is used as a promising tool for numerical optimization of such problems. The objective of the study is to determine effective, general design methods for determining the optimal design of thin parts of I.C. engine that minimizes the total radiated acoustic power. Variable attached discrete masses are considered. Acoustic response is minimized either at a single frequency or first five natural frequencies. Radiated sound power is calculated using a boundary element method, in conjunction with a finite element solver ANSYS for the solution of the structural acoustical problem.
Study of Fuel Temperature Effects on Fuel Injection, Combustion and Emissions of Direct-Injection Diesel Engines
Authors: Chen Gong
Published: January 2009

The influence of inlet liquid fuel temperature on direct-injection diesel engines can be noticeable and significant. The work in this paper investigates the effects of inlet fuel temperature on fuel injection, in-cylinder combustion, and performance and emissions of medium-speed diesel engines. An enhanced understanding and simplified modeling of the variations in main fuel injection parameters affected by inlet fuel temperature are developed. The study indicates that the main affected injection parameters include the injector injection timings, the fuel injection rate, the fuel injection duration, and the injection spray atomization. The primary fuel temperature effects on the injection parameters are from the fuel bulk modulus of elasticity and the density with the fuel viscosity less significant as the injector nozzle flow is in a turbulent region. The developed models can predict the changes in the injection parameters versus fuel temperature. As inlet fuel temperature increases, the nozzle fuel-injection-start timing is predicted to be retarded, the injection rate to be reduced, and the needle-lift duration to be prolonged from the baseline. The variation trends of the engine performance and emissions versus fuel temperature are analyzed by considering its consequent effect on in-cylinder combustion processes. It is predicted that raising fuel temperature would result in an increase in CO, HC, PM and smoke emissions, and in a decrease in NOx. The experimental results of the output performance and emissions from testing a medium-speed four-stroke diesel engine agreed with the trends analytically predicted. The understanding and models developed can apply to compression-ignition direct-injection liquid fuel engines in general.
A Comprehensive Thermodynamic Approach to Acoustic Cavitation Simulation in High-Pressure Injection Systems by a Conservative Homogeneous Barotropic-Flow Model
Authors: Catania Andrea E. , Ferrari Alessandro , Manno Michele , Spessa Ezio
Published: January 2009

A general conservative numerical model for simulation of transmission-line unsteady fluid-dynamics has been developed and applied to high-pressure injection systems. A comprehensive thermodynamic approach for modeling acoustic cavitation, i.e. cavitation induced by wave propagation, was proposed on the basis of a homogeneous barotropic mixture model of a pure liquid in equilibrium with its vapor and a gas, both dissolved and undissolved. For the pure liquid flow simulation outside the cavitation regions, or in the absence of these, temperature variations due to compressibility effects were taken into account, for the first time in injection system simulation, through a thermodynamic state equation which was derived from energy considerations. Nevertheless, in the cavitation regions, an isothermal flow was retained which is consistent with negligible thermal effects due to vaporization because of the tiny amounts of liquid involved. A novel implicit, conservative, one step, symmetrical and trapezoidal scheme of the second-order accuracy was applied to solve the hyperbolic partial differential equations governing the pipe flows. It can also be enhanced at a high-resolution level. The numerical model was applied to wave propagation and cavitation simulation in a high-pressure injection system of the pump-line-nozzle type for light and medium duty vehicles. The system was of relevance to the model assessment because it presented severely cavitating flow conditions. The predicted pressure time histories at two pipe locations and injector needle lift were compared to experimental results, substantiating the validity and robustness of the developed conservative model in simulating cavitation inception and desinence with great degree of accuracy. Cavitation transients and the flow discontinuities induced by them were numerically analyzed and discussed.
In Vitro Activities of Retigeric Acid B Alone and in Combination with Azole Antifungal Agents against
Candida albicans
Authors: Sun Lingmei , Sun Shujuan , Cheng Aixia , Wu Xiuzhen , Zhang Yu , Lou Hongxiang
Published: January 2009

The vitro antifungal activity of retigeric acid B (RAB), a pentacyclic triterpenoid from the lichen species
Lobaria kurokawae
, was evaluated alone and in combination with fluconazole, ketoconazole, and itraconazole against
Candida albicans
using checkerboard microdilution and time-killing tests. The MICs for RAB against 10 different
C. albicans
isolates ranged from 8 to 16 μg/ml. A synergistic action of RAB and azole was observed in azole-resistant strains, whereas synergistic or indifferent effects were observed in azole-sensitive strains when interpreted by a separate approach of the fractional inhibitory concentration index and Δ
E
model (the difference between the predicted and measured fungal growth percentages). In time-killing tests, we used both colony counts and a colorimetric assay to evaluate the combinational antifungal effects of RAB and azoles, which further confirmed their synergistic interactions. These findings suggest that the natural product RAB may play a certain role in increasing the susceptibilities of azole-resistant
C. albicans
strains.
Accelerated Metabolism of Voriconazole and Its Partial Reversal by Cimetidine
Authors: Moriyama Brad , Elinoff Jason , Danner Robert L. , Gea-Banacloche Juan , Pennick Gennethel , Rinaldi Michael G. , Walsh Thomas J.
Published: January 2009

We report a case of accelerated metabolism of voriconazole during therapy for invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target voriconazole levels were restored with high dosages of voriconazole (up to 40 mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450 enzyme inhibitor.
A Novel Gene,erm(41), Confers Inducible Macrolide Resistance to Clinical Isolates ofMycobacterium abscessusbut Is Absent fromMycobacterium chelonae
Authors: Nash Kevin A. , Brown-Elliott Barbara A. , Wallace Richard J.
Published: January 2009

Mycobacterium abscessusinfections tend to respond poorly to macrolide-based chemotherapy, even though the organisms appear to be susceptible to clarithromycin. Circumstantial evidence suggested that at least someM. abscessusisolates might be inducibly resistant to macrolides. Thus, the purpose of this study was to investigate the macrolide phenotype ofM. abscessusclinical isolates. Inducible resistance to clarithromycin (MIC > 32 μg/ml) was found for 7 of 10 clinical isolates ofM. abscessuspreviously considered susceptible; the remaining 3 isolates were deemed to be susceptible (MIC ≤ 0.5 μg/ml). Inducible resistance was conferred by a novelermgene,erm(41), which was present in all 10 isolates and in an isolate ofMycobacterium bolletii(M. abscessustype II). However, theerm(41) alleles were nonfunctional in the three susceptibleM. abscessusisolates. No evidence oferm(41) was found inMycobacterium chelonae, and an isolate ofMycobacterium massilienseappeared to be anerm(41) deletion mutant. Expression oferm(41) inM. abscessusconferred resistance to clarithromycin and erythromycin and the ketolide HMR3004. However, this species was found to be intrinsically resistant, independent oferm(41), to clindamycin, quinupristin (streptogramin B), and telithromycin. The ability to confer resistance to clindamycin and telithromycin, but not quinupristin, was demonstrated by expressingerm(41) inMaycobacterium smegmatis. Exposure ofM. abscessusto the macrolide-lincosamide-streptogramin B-ketolide agents increased the levels oferm(41) mRNA 23- to 250-fold within 24 h. The inducible macrolide resistance phenotype of someM. abscessusisolates may explain the lack of efficacy of macrolide-based chemotherapy against this organism.
Mutations in Three Distinct Loci Cause Resistance to Peptide Deformylase Inhibitors inBacillus subtilis
Authors: Duroc Yann , Giglione Carmela , Meinnel Thierry
Published: January 2009

Bacillus subtilismutants with resistance against peptide deformylase inhibitors were isolated. All showed a bypass of the pathway through mutations in three genes required for formylation of Met-tRNAfMet,fmt, folD, andglyA. glyAcorresponds to a yet uncharacterized locus inducing resistance. The bypass of formylation caused robust fitness reduction but was not accompanied by alterations of the transcription profile. A subtle adaptation of the enzymes of the intermediary metabolism was observed.
Comparison of the Roll Plate Method to the Sonication Method To Diagnose Catheter Colonization and Bacteremia in Patients with Long-Term Tunnelled Catheters: a Randomized Prospective Study
Authors: Slobbe Lennert , el Barzouhi Abdelilah , Boersma Eric , Rijnders Bart J. A.
Published: January 2009

Diagnosing catheter-related bloodstream infection (CRBSI) still often involves tip culture. The conventional method is the semiquantitative roll plate method. However, the use of a quantitative sonication technique could have additional value, as it may detect endoluminal microorganisms more easily. Because endoluminal infection tends to occur in long-term central venous catheters, we compared both techniques for patients with long-term tunnelled catheters. For 313 consecutive Hickman catheter tips from 279 hematological patients, colonization detection rates were compared by performing both techniques in a random order, using conventional detection cutoffs. Additionally, for the subgroup of patients with clinical suspicion of CRBSI (
n
= 89), the diagnostic values of both techniques were compared. The overall tip colonization rate was 25%. For each technique, the detection rate tended to be better if that technique was performed first. The diagnostic performance for the subgroup of patients with clinical suspicion of CRBSI was limited and not different for both methods. Sensitivity and specificity were 45% and 84%, respectively, for sonication versus 35% and 90%, respectively, for the roll plate technique. The fact that 35 of 40 patients with CRBSI received antimicrobial therapy before catheter removal and tip culture, in an attempt to salvage the catheter, may partly explain this poor performance. No differences were observed when catheters were stratified according to in situ time below or above the median of 4 weeks. The sonication culture technique was not better than the roll plate method to diagnose tip colonization or CRBSI in patients with long-term tunnelled catheters.
Quasi-elastic neutron scattering (QENS) studies on the 1:1 tetramethylpyrazine–1,2,4,5-tetracyanobenzene complex
Authors: Krawczyk Jan , Nowina Konopka Małgorzata , Janik Jerzy A. , Steinsvoll Olav , Bator Grażyna , Pawlukojć Andrzej , Grech Eugeniusz , Nowicka-Scheibe Joanna , Sobczyk Lucjan
Published: January 2009

The quasi-elastic neutron scattering (QENS) spectra over the temperature range 10–270 K were studied. The activation energies for the stochastic jumps of methyl groups in neat tetramethylpyrazine (TMP) and in the complex TMP·TCNB (tetracyanobenzene) were estimated to be equal to 5.0 ± 1.2 and 2.2 ± 1.1 kJ/mol, respectively, which means that the methyl groups behave in the complex more freely than in TMP. This conclusion is in good agreement with frequencies of the CH3 torsional modes recorded in the inelastic neutron scattering (INS) spectra. They are also confirmed by the DFT calculations for the crystalline state of TMP and TMP·TCNB, although the calculations overestimate the effect of the crystalline state on the CH3 torsional frequencies. The difference in the behavior of the methyl groups in neat TMP and TMP·TCNB is also reflected in the blue-shift of the ν(CH) stretching vibration modes.
An exploratory study of the safety, tolerability and bioactivity of a single intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic macular oedema
Authors: Do D V , Nguyen Q D , Shah S M , Browning D J , Haller J A , Chu K , Yang K , Cedarbaum J M , Vitti R L , Ingerman A , Campochiaro P A
Published: January 2009

Aim:

The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO).

Methods:

Five subjects with DMO, foveal thickness ⩾250 μm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT.

Results:

Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 μm. At 4 weeks after injection, the median excess FTH was 59 μm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 μm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters).

Conclusions:

A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.
Analysis of soluble vascular endothelial growth factor receptor-1 secreted from cultured corneal and oral mucosal epithelial cell sheets in vitro
Authors: Kanayama S , Nishida K , Yamato M , Hayashi R , Maeda N , Okano T , Tano Y
Published: January 2009

Background:

In clinical trials, eyes transplanted with cultured oral mucosal epithelial cell sheets have shown increased neovascularisation compared with eyes treated with cultured corneal epithelial cell sheets. As reported recently, soluble vascular endothelial growth factor receptor-1 (soluble VEGFr-1) is a main factor to maintain a corneal avascularity.

Aim:

To investigate soluble VEGFr-1 of cultured corneal epithelial cells (CCE) and cultured oral mucosal epithelial cells (COE) in vitro.

Methods:

Rabbit corneal and oral mucosal epithelial cells were co-cultured with mitomycin C-treated NIH/3T3 cells on culture plates. After CCE and COE were multilayered, culture medium was replaced by basal medium and incubated. Protein secretion of soluble VEGFr-1 was assessed in conditioned medium from CCE and COE by ELISA. Angiogenic potential was examined by invasion, migration assays with human umbilical vein endothelial cells (HUVECs) in addition to recombinant soluble VEGFr-1.

Results:

CCE secreted a significantly higher amount of soluble VEGFr-1 than did COE. Recombinant soluble VEGFr-1 significantly suppressed HUVEC migration induced by COE, without suppression in CCE. In conclusion, these findings suggest that low protein levels of soluble VEGFr-1 may lead to corneal neovascularisation after COE sheet transplantation.
Venous invasion detection in colorectal cancer: which approach, which technique?
Authors: Puppa G , Caneva A , Colombari R
Published: January 2009

Colorectal cancer is one of the most commonly diagnosed human malignancies and is a major cause of death worldwide. A high-quality macroscopic examination and histopathology report enables correct tumour staging, affects patient prognosis, and provides indications for further therapy. Although venous invasion is a stage-independent indicator of poor prognosis that identifies high-risk patients for visceral metastases, it is not a stage-influencing factor. Accordingly the use of special stains to facilitate the detection of venous invasion is not universally recommended and therefore not widely used in routine histopathological analysis. In this report based on a case presentation, the different approaches and techniques for detecting venous invasion are presented and discussed.
Ethical aspects of research into Alzheimer disease. A European Delphi Study focused on genetic and non-genetic research
Authors: van der Vorm A , Vernooij-Dassen M J F J , Kehoe P G , Rikkert M G M Olde , van Leeuwen E , Dekkers W J M
Published: January 2009

Background:

Although genetic research into Alzheimer disease (AD) is increasing, the ethical aspects of this kind of research and the differences between ethical issues related to genetic and non-genetic research into AD have not yet received much attention.

Objectives:

(1) To identify and compare the five ethical issues considered most important by surveyed expert panellists in non-genetic and genetic AD research and (2) to compare our empirical findings with ethical issues in genetic research in general as described in the literature.

Method:

A modified Delphi study in two rounds

Results:

Genetic and non-genetic research into AD generated an approximately equal number of topics with a considerable overlap. Different priorities in the ethics of both types of research were found. Genetic research raised new topics such as “confidentiality of genetic information” and “implications of research for relatives” which changes the impact and application of existing ethical topics such as “informed consent” and is judged to have more impact on both individuals and society. A difference with the results of more theoretical approaches on ethical aspects related to AD research was also found.

Conclusions:

Different priorities are given to ethical issues in genetic and non-genetic research. These arise partly because genetic research causes unique and new questions, mostly related to the position of family members and the status of and access to genetic information. Differences found between the results of our empirical study and the more theoretical literature, suggest an additional value for empirical research in medical ethics.
Stiffness constants and interaction factors for vertical response of pile groups
Authors: Sharnouby Bahaa El , Novak Milos
Published: January 2009

Stiffness constants and flexibility coefficients of single piles and interaction factors are presented to facilitate the analysis of pile groups subjected to static vertical loads. A continuous transition from friction to end-bearing piles is accounted for. A new type of interaction factor, established from subgroups of five piles, is introduced for end-bearing piles. This interaction factor allows for the stiffening effect of the piles occurring between the two reference piles. This feature improves the accuracy of group analysis for end-bearing piles. Numerical results for axially loaded single piles and pile groups are presented for a wide range of pile and soil parameters. The results are applicable toboth rigid and flexible caps. Key words: piles, pile group, settlement, interaction
Maternal obesity downregulates myogenesis and β-catenin signaling in fetal skeletal muscle
Authors: Tong Jun F. , Yan Xu , Zhu Mei J. , Ford Stephen P. , Nathanielsz Peter W. , Du Min
Published: January 2009

Skeletal muscle is one of the primary tissues responsible for insulin resistance and type 2 diabetes (T2D). The fetal stage is crucial for skeletal muscle development. Obesity induces inflammatory responses, which might regulate myogenesis through Wnt/β-catenin signaling. This study evaluated the effects of maternal obesity (>30% increase in body mass index) during pregnancy on myogenesis and the Wnt/β-catenin and IKK/NF-κB pathways in fetal skeletal muscle using an obese pregnant sheep model. Nonpregnant ewes were assigned to a control group (C; fed 100% of National Research Council recommendations; n = 5) or obesogenic (OB; fed 150% of National Research Council recommendations; n = 5) diet from 60 days before to 75 days after conception (term ∼148 days) when fetal semitendenosus skeletal muscle was sampled for analyses. Myogenic markers including MyoD, myogenin, and desmin contents were reduced in OB compared with C fetal semitendenosus, indicating the downregulation of myogenesis. The diameter of primary muscle fibers was smaller in OB fetal muscle. Phosphorylation of GSK3β was reduced in OB compared with C fetal semitendenosus. Although the β-catenin level was lower in OB than C fetal muscle, more β-catenin was associated with FOXO3a in the OB fetuses. Moreover, we found phosphorylation levels of IKKβ and RelA/p65 were both increased in OB fetal muscle. In conclusion, our data showed that myogenesis and the Wnt/β-catenin signaling pathway were downregulated, which might be due to the upregulation of inflammatory IKK/NF-κB signaling pathways in fetal muscle of obese mothers.
Regulation of the proprotein convertase subtilisin/kexin type 9 in intestinal epithelial cells
Authors: Leblond François , Seidah Nabil G. , Précourt Louis-Philippe , Delvin Edgard , Dominguez Michel , Levy Emile
Published: January 2009

Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLr) in hepatocytes and increases plasma LDL cholesterol. It is not clear, however, whether PCSK9 plays a role in the small intestine. Here, we characterized the patterns of variations of PCSK9 and LDLr in fully differentiated Caco-2/15 cells as a function of various potential effectors. Cholesterol (100 μM) solubilized in albumin or micelles significantly downregulated PCSK9 gene (30%, P < 0.05) and protein expression (50%, P < 0.05), surprisingly in concert with a decrease in LDLr protein levels (45%, P < 0.05). Cells treated with 25-hydroxycholesterol (50 μM) also displayed significant reduction in PCSK9 gene (37%, P < 0.01) and protein (75% P < 0.001) expression, whereas LDLr showed a decrease at the gene (30%, P < 0.05) and protein (57%, P < 0.01) levels, respectively. The amounts of PCSK9 mRNA and protein in Caco-2/15 cells were associated to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein-2 (SREBP-2) that can transcriptionally activate PCSK9 via sterol-regulatory elements located in its proximal promoter region. On the other hand, depletion of cholesterol content by hydroxypropyl-β-cyclodextrin upregulated PCSK9 transcripts (20%, P < 0.05) and protein mass (540%, P < 0.001), in parallel with SREBP-2 protein levels. The addition of bile acids (BA) taurocholate and deoxycholate to the apical culture medium lowered PCSK9 gene expression (25%, P < 0.01) and raised PCSK9 protein expression (30%, P < 0.01), respectively, probably via the modulation of farnesoid X receptor. Furthermore, unconjugated and conjugated BA exhibited different effects on PCSK9 and LDLr. Altogether, these data indicate that intestinal PCSK9 is highly modulated by sterols and emphasize the distinct effects of BA species.
Lysophosphatidyl choline modulates mechanosensitive L-type Ca2+ current in circular smooth muscle cells from human jejunum
Authors: Kraichely Robert E. , Strege Peter R. , Sarr Michael G. , Kendrick Michael L. , Farrugia Gianrico
Published: January 2009

The L-type Ca2+ channel expressed in gastrointestinal smooth muscle is mechanosensitive. Direct membrane stretch and shear stress result in increased Ca2+ entry into the cell. The mechanism for mechanosensitivity is not known, and mechanosensitivity is not dependent on an intact cytoskeleton. The aim of this study was to determine whether L-type Ca2+ channel mechanosensitivity is dependent on tension in the lipid bilayer in human jejunal circular layer myocytes. Whole cell currents were recorded in the amphotericin-perforated-patch configuration, and lysophosphatidyl choline (LPC), lysophosphatidic acid (LPA), and choline were used to alter differentially the tension in the lipid bilayer. Shear stress (perfusion at 10 ml/min) was used to mechanostimulate L-type Ca2+ channels. The increase in L-type Ca2+ current induced by shear stress was greater in the presence of LPC (large head-to-tail proportions), but not LPA or choline, than in the control perfusion. The increased peak Ca2+ current also did not return to baseline levels as in control conditions. Furthermore, steady-state inactivation kinetics were altered in the presence of LPC, leading to a change in window current. These findings suggest that changes in tension in the plasmalemmal membrane can be transmitted to the mechanosensitive L-type Ca2+ channel, leading to altered activity and Ca2+ entry in the human jejunal circular layer myocyte.
Hypoxia stimulates via separate pathways ERK phosphorylation and NF-κB activation in skeletal muscle cells in primary culture
Authors: Osorio-Fuentealba César , Valdés Juan Antonio , Riquelme Denise , Hidalgo Jorge , Hidalgo Cecilia , Carrasco María Angélica
Published: January 2009

Mammalian cells sense oxygen levels and respond to hypoxic conditions through the regulation of multiple signaling pathways and transcription factors. Here, we investigated the effects of hypoxia on the activity of two transcriptional regulators, ERK1/2 and NF-κB, in skeletal muscle cells in primary culture. We found that hypoxia significantly enhanced ERK1/2 phosphorylation and that it stimulated NF-κB-dependent gene transcription as well as nuclear translocation of a green fluorescent protein-labeled p65 NF-κB isoform. Phosphorylation of ERK1/2- and NF-κB-dependent transcription by hypoxia required calcium entry through L-type calcium channels. Calcium release from ryanodine-sensitive stores was also necessary for ERK1/2 activation but not for NF-κB-dependent-transcription. N-acetylcysteine, a general scavenger of reactive oxygen species, blocked hypoxia-induced ROS generation but did not affect the stimulation of ERK1/2 phosphorylation induced by hypoxia. In contrast, NF-κB activation was significantly inhibited by N-acetylcysteine and did not depend on ERK1/2 stimulation, as shown by the lack of effect of the upstream ERK inhibitor U-0126. These separate pathways of activation of ERK1/2 and NF-κB by hypoxia may contribute to muscle adaptation in response to hypoxic conditions.
Initial Investigation of Using Planar Interdigital Sensors for Assessment of Quality in Seafood
Authors: Syaifudin A. R. Mohd , Jayasundera K. P. , Mukhopadhyay S. C.
Published: January 2009

A planar interdigital sensor‐based sensing system has been fabricated for assessment of seafood quality. Our main objective is to sense the molecule of domoic acid presence in mussels. Three peptide derivatives namely sarcosine, proline, and hydroxylproline were used for the initial studies which are structurally closely related to our target molecule. The proline molecule is arguably the most important amino acid in peptide conformation, containing the basic structural similarity to the domoic acid. Three novel interdigital sensors have been designed and fabricated. The initial result shows that sensors respond very well to the chemicals and it is possible to discriminate the different chemicals from the output of the sensor. Results from the analysis have shown that Sensor_1 has better sensitivity compared to other sensors. Sensor_1 was chosen for further analysis with real mussels. The changes in sensor impedance were then analysed with real mussels before and after adding the proline. The presence of proline on the mussel samples was detected by the sensor. Results also showed a good correlation of R2 = 0.717 between sensitivity and sample thickness.
Upper and Lower Bound Limit Loads for Thin-Walled Pressure Vessels Used for Aerosol Cans
Authors: Hardy Stephen John , Abdusslam Ragba Mohamed
Published: January 2009

The elastic compensation method proposed by Mackenzie and Boyle is used to estimate the upper and lower bound limit (collapse) loads for one-piece aluminium aerosol cans, which are thin-walled pressure vessels subjected to internal pressure loading. Elastic-plastic finite element predictions for yield and collapse pressures are found using axisymmetric models. However, it is shown that predictions for the elastic-plastic buckling of the vessel base require the use of a full three-dimensional model with a small unsymmetrical imperfection introduced. The finite element predictions for the internal pressure to cause complete failure via collapse fall within the upper and lower bounds. Hence the method, which involves only elastic analyses, can be used in place of complex elastic-plastic finite element analyses when upper and lower bound estimates are adequate for design purposes. Similarly, the lower bound value underpredicts the pressure at which first yield occurs.
Strain-Encoded MRI for Evaluation of Left Ventricular Function and Transmurality in Acute Myocardial Infarction
Authors: Neizel Mirja , Lossnitzer Dirk , Korosoglou Grigorios , Schäufele Tim , Peykarjou Hooman , Steen Henning , Ocklenburg Christina , Giannitsis Evangelos , Katus Hugo A. , Osman Nael F.
Published: January 2009

Background—

Strain-encoded imaging (SENC) is a new technique for myocardial deformation analysis in cardiac MRI. The aim of the study was, therefore, to evaluate whether myocardial deformation imaging performed by SENC allows for quantification of regional left ventricular function and is related to transmurality states of infarcted tissue in patients with acute myocardial infarction.

Methods and Results—

Cardiac MRI was performed in 38 patients with acute myocardial infarction 3�1 days after successful reperfusion using a clinical 1.5-T MRI scanner. Ten healthy volunteers served as controls. SENC is a technique that directly measures peak circumferential strain from long-axis views and peak longitudinal strain from short-axis views. Measurements were obtained for each segment in a modified 17-segment model. Wall motion and infarcted tissue were evaluated semiquantitatively from steady-state free-precession cine sequences and contrast-enhanced MR images and were then related to myocardial strain. Comparison of peak circumferential strain assessed by SENC and MR tagging was performed. In total, 456 segments were analyzed. Peak circumferential and longitudinal strain calculated from SENC images was significantly different in regions defined as normokinetic, hypokinetic, or akinetic (
P
<0.001). A cutoff peak systolic circumferential strain value of −10% differentiated nontransmural from transmural infarcted myocardium, with a sensitivity of 97% and a specificity of 94%. Strain analysis of SENC and MR tagging correlated well (
r
=0.76) with narrow limits of agreement (−9.9% to 8.5%).

Conclusions—

SENC provides rapid and objective quantification of regional myocardial function and allows discrimination between different transmurality states in patients with acute myocardial infarction.
Strain-Encoded Cardiac MRI as an Adjunct for Dobutamine Stress Testing
Authors: Korosoglou Grigorios , Lossnitzer Dirk , Schellberg Dieter , Lewien Antje , Wochele Angela , Schaeufele Tim , Neizel Mirja , Steen Henning , Giannitsis Evangelos , Katus Hugo A. , Osman Nael F.
Published: January 2009

Background—

High-dose dobutamine stress MRI is safe and feasible for the diagnosis of coronary artery disease (CAD) in humans. However, the assessment of cine scans relies on the visual interpretation of regional wall motion, which is subjective. Recently, strain-encoded MRI (SENC) has been proposed for the direct color-coded visualization of myocardial strain. The purpose of our study was to compare the diagnostic value of SENC with that provided by conventional wall motion analysis for the detection of inducible ischemia during dobutamine stress MRI.

Methods and Results—

Stress-induced ischemia was assessed by wall motion analysis and by SENC in 101 patients with suspected or known CAD and in 17 healthy volunteers who underwent dobutamine stress MRI in a clinical 1.5-T scanner. Quantitative coronary angiography deemed as the standard reference for the presence or absence of significant CAD (≥50% diameter stenosis). On a coronary vessel level, SENC detected inducible ischemia in 86 of 101 versus 71 of 101 diseased coronary vessels (
P
<0.01 versus cine) and showed normal strain response in 189 of 202 versus 194 of 202 vessels with <50% stenosis (
P
=NS versus cine). On a patient level, SENC detected inducible ischemia in 63 of 64 versus 55 of 64 patients with CAD (
P
<0.05 versus cine) and showed normal strain response in 32 of 37 versus 34 of 37 patients without CAD (
P
=NS versus cine). Quantification analysis demonstrated a significant correlation between strain rate reserve and coronary artery stenosis severity (
r
2
=0.56,
P
<0.001), and a cutoff value of strain rate reserve of 1.64 was deemed as a highly accurate marker for the detection of ≥50% stenosis (area under the curve, 0.96; SE, 0.01; 95% CI, 0.94 to 0.98;
P
<0.001).

Conclusions—

The direct color-coded visualization of strain on MR images is a useful adjunct for dobutamine stress MRI, which provides incremental value for the detection of CAD compared with conventional wall motion readings on cine images.
Prevalence of Coronary Artery Disease Assessed by Multislice Computed Tomography Coronary Angiography in Patients With Paroxysmal or Persistent Atrial Fibrillation
Authors: Nucifora Gaetano , Schuijf Joanne D. , Tops Laurens F. , van Werkhoven Jacob M. , Kajander Sami , Jukema J. Wouter , Schreur Joop H.M. , Heijenbrok Mark W. , Trines Serge A. , Gaemperli Oliver , Turta Olli , Kaufmann Philipp A. , Knuuti Juhani , Schalij Martin J. , Bax Jeroen J.
Published: January 2009

Background—

Although atrial fibrillation (AF) has been linked to underlying coronary artery disease (CAD), data supporting this association have been based on ECG and clinical history for the definition of CAD rather than direct visualization of atherosclerosis.

Methods and Results—

The prevalence of CAD among patients with paroxysmal or persistent AF and without history of CAD was evaluated using multislice computed tomography. Multislice computed tomography was performed in 150 patients with AF (61�11 years, 67% males, 58% asymptomatic) with predominantly low (59%) or intermediate (25%) pretest likelihood of CAD. CAD was classified as obstructive (≥50% luminal narrowing) or not. A population of 148 patients without history of AF, similar to the AF group as to age, gender, symptomatic status, and pretest likelihood, served as a control group. Logistic regression analysis was applied to evaluate the relationship between demographic and clinical data and the presence of obstructive CAD. On the basis of multislice computed tomography, 18% of patients with AF were classified as having no CAD, whereas 41% showed nonobstructive CAD and the remaining 41% had obstructive CAD. Among patients without AF, 32% were classified as having no CAD, whereas 41% showed nonobstructive CAD and 27% had obstructive CAD (
P
=0.010 compared with patients with AF). At logistic regression analysis, age, male gender, and the presence of AF were significantly related to obstructive CAD.

Conclusion—

A higher prevalence of obstructive CAD was observed among patients with AF, confirming the hypothesis that AF could be a marker of advanced coronary atherosclerosis.