bluuebunny/crossref_metadata_2025 huggingface dataset:
AMPHIDINIUM REVISITED. I. REDEFINITION OF AMPHIDINIUM (DINOPHYCEAE) BASED ON CLADISTIC AND MOLECULAR PHYLOGENETIC ANALYSES1
Authors: Jørgensen Mårten Flø , Murray Shauna , Daugbjerg Niels
Published: November 2005

Members of Amphidinium Claparède and Lachmann constitute a major part of sand‐dwelling benthic dinoflagellates worldwide. The genus is traditionally defined by its small epicone size, not exceeding one third of the total cell length. It has long been suspected that this functional definition does not reflect phylogeny, yet the problem of identifying the type species A. operculatum and closely related species has until now hindered attempts to redefine the genus. In this study 12 Amphidinium species were examined using phylogenetic analyses based on nuclear‐encoded, partial, large subunit (LSU) rDNA, with a further six Amphidinium species being included in a morphological cladistic analysis. The species selected represented taxa with a range of morphological dissimilar epicone forms. Both cladistic analysis and analyses based on partial LSU rDNA revealed that Amphidinium species with minute left‐deflected epicones formed a monophyletic clade that included the type species. Amphidinium species with other epicone types were found to be unrelated to this clade. The type species A. operculatum was identified based on general cell shape and size, position of a dark organelle previously defined as a stigma, and origin of the sulcus. The description of A. elegans by Grell and Wohlfarth‐Bottermann was found to be identical to it. A species fitting the original description of A. operculatum was cultured and included in the analyses. Based on cladistic and molecular analyses, it grouped together with all other species with minute left‐deflected epicones, and this group constitutes the true genus Amphidinium sensu stricto. An emendation of the genus definition is presented.
PHYLOGENETIC ANALYSIS OF A FREE‐LIVING STRAIN OF SYMBIODINIUM ISOLATED FROM JIAOZHOU BAY, P.R. CHINA1
Authors: Santos Scott R.
Published: November 2005

Recently, the isolation of a free‐living strain of symbiotic dinoflagellate belonging to the genus Symbiodinium was reported. Although the specimen procured and characterization from Jiaozhou Bay, P.R. China is a Symbiodinium spp., the manner in which this isolate was classified is inconsistent with the currently used and accepted Symbiodinium cladal nomenclature. To avert unnecessary confusion in the field, I place this important scientific contribution into the proper context and state of Symbiodinium research.
Comparison of bacterial plaque samples from titanium implant and tooth surfaces by different methods
Authors: Gerber Jeanne , Wenaweser Doris , Heitz‐Mayfield Lisa , Lang Niklaus P. , Rutger Persson G.
Published: November 2005

Abstract: Studies have shown similarities in the microflora between titanium implants or tooth sites when samples are taken by gingival crevicular fluid (GCF) sampling methods. The purpose of the present study was to study the microflora from curette and GCF samples using the checkerboard DNA–DNA hybridization method to assess the microflora of patients who had at least one oral osseo‐integrated implant and who were otherwise dentate. Plaque samples were taken from tooth/implant surfaces and from sulcular gingival surfaces with curettes, and from gingival fluid using filter papers. A total of 28 subjects (11 females) were enrolled in the study. The mean age of the subjects was 64.1 years (SD±4.7). On average, the implants studied had been in function for 3.7 years (SD±2.9). The proportion of Streptococcus oralis (P<0.02) and Fusobacterium periodonticum (P<0.02) was significantly higher at tooth sites (curette samples). The GCF samples yielded higher proportions for 28/40 species studies (P‐values varying between 0.05 and 0.001). The proportions of Tannerella forsythia (T. forsythensis), and Treponema denticola were both higher in GCF samples (P<0.02 and P<0.05, respectively) than in curette samples (implant sites). The microbial composition in gingival fluid from samples taken at implant sites differed partly from that of curette samples taken from implant surfaces or from sulcular soft tissues, providing higher counts for most bacteria studied at implant surfaces, but with the exception of Porphyromonas gingivalis. A combination of GCF and curette sampling methods might be the most representative sample method.
Prostaglandin D2 pathway and peroxisome proliferator‐activated receptor γ‐1 expression are induced by mechanical loading in an osteoblastic cell line
Authors: Siddhivarn Chitpol , Banes Albert , Champagne Catherine , Riché Estelle L. , Weerapradist Woranut , Offenbacher Steven
Published: November 2005

Objective:  The hypothesis underlying the current study was that the arachidonic acid cascade, specifically activation of the prostaglandin (PG) D2 pathway in osteoblasts, is an anabolic signal induced by mechanical loading.

Background:  Previous studies have shown that mechanical loading of osteoblasts triggers cyclooxygenase (COX)‐2, PGE2 and prostacyclin (PGI2) synthesis. Since modest mechanical loading of osteoblasts promotes bone formation, we sought to determine whether mechanical stress activates the osteoblastic PGD2 pathway resulting in the synthesis of osteogenic cyclopentenones, including Δ12PGJ2.

Methods:  Osteoblast monolayers were stretched using a Bioflex apparatus at a frequency of 1 Hz with 1% elongation. Cells and cell media were collected at various time points: 5, 10, 15, 30 min; and 1, 4, 16, 24 h. RNA was extracted for quantitative reverse transcriptase–polymerase chain reaction (RT–PCR). In certain experiments, cells were pre‐labeled with 14C arachidonic acid prior to stretching. Radiolabeled metabolites in cell media were identified by reverse‐phase high performance liquid chromatography (RP‐HPLC). Osteoblasts were evaluated for an induction in bone nodule formation by stretching.

Results:  Mechanical strain significantly increased mRNA expression of COX‐1, COX‐2, PGD2 synthase and peroxisome proliferator‐activated receptor (PPAR) γ‐1, but not of PPARγ‐2 as compared to control unstretched cells (p < 0.05). Mechanical loading stimulated the release of PGE2, PGD2 and the PGD2 metabolite Δ12PGJ2. Mechanical strain resulted in the induction of bone nodules.

Conclusions:  This report indicates that mechanical loading of osteoblasts results in activation of PGD2 and the concomitant expression of transcription factor PPARγ‐1 mRNA. The coordinated synthesis of Δ12PGJ2, a natural ligand for PPARγ‐1, with the increased expression of PPARγ‐1, suggests that biomechanical transduction pathways that initially involve the activation of cyclooxygenases may also involve the activation of the Δ12PGJ2–PPAR pathway.
Increased infiltration of CD1d+ and natural killer T cells in periodontal disease tissues
Authors: Amanuma R. , Nakajima T. , Yoshie H. , Yamazaki K.
Published: November 2005

Background:  Natural killer T (NKT) cells are a unique T lymphocyte subset that has been implicated in the regulation of immune responses associated with a broad range of diseases including autoimmunity, infectious diseases, and cancer. In contrast to conventional T cells, NKT cells are reactive to major histocompatibility complex (MHC) class I‐like molecule CD1d. Considering the periodontitis having both aspects of infection and autoimmunity in nature, CD1d and reactive NKT cells are of particular importance.

Objective:  The aim of the present study was to examine whether the expression of CD1 isoforms and Vα24+ invariant NKT cells is associated with different disease entities, namely gingivitis and periodontitis.

Material and Methods:  Immunohistochemical analysis was performed on cryostat sections of gingival tissues from 19 patients with periodontitis and eight patients with gingivitis using antibodies to CD1a, b, c, d, Vα24+ invariant NKT cells, CD83, CD3 and CD19.

Results:  Although all four subsets of CD1 molecules were expressed in periodontal lesions, CD1d was most abundant. CD1d expression was more frequent in periodontitis than gingivitis and increased together with increase of invariant NKT cell infiltration. Double immunohistochemical staining showed co‐expression of CD1d and CD19 on identical cells and proximate infiltration of CD1d+ and invariant NKT cells.

Conclusion:  These findings suggest that CD1d‐expressing B cells could activate NKT cells by CD1d‐restricted manner and this NKT cell activation may play roles in pathogenesis of periodontal diseases.
Maturation‐state dependent response of human periodontal ligament cells to an intermittent parathyroid hormone exposure in vitro
Authors: Lossdörfer S , Stier S , Götz W , Jäger A
Published: November 2005

Background and objectives:  Parathyroid hormone (parathyroid hormone) has been shown to be capable of exerting anabolic effects on bone when administered intermittently. We hypothesized that parathyroid hormone will modulate the response of periodontal ligament cells in terms of anabolic effects with respect to proliferation, differentiation and the production of key regulatory factors of bone remodeling such as osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) in a maturation‐state dependent manner.

Methods:  Periodontal ligament cells were cultured from human bicuspids obtained from six patients. Following characterization, confluent and preconfluent periodontal ligament cells were challenged with parathyroid hormone (1–34) for 0, 1, 3, 6 or 24 h within three incubation cycles of 48 h each. At harvest, the cell number, alkaline phosphatase specific activity and osteocalcin, osteoprotegerin and RANKL production were determined by means of semiquantitative polymerase chain reaction (PCR) and immunoassays. Dermal fibroblasts and MG63 osteoblast‐like cells served as a reference.

Results:  Intermittent parathyroid hormone treatment of confluent periodontal ligament cells caused a significant increase in proliferation (+32% maximum) whereas alkaline phosphatase activity, osteocalcin and osteoprotegerin decreased at the transcriptional and translational level (−59.7% maximum). In preconfluent periodontal ligament cells, parathyroid hormone induced a decrease in proliferation (−66.3% maximum) but an increase in differentiation and osteoprotegerin production (+49.2% maximum). RANKL was hardly detectable and unaffected by parathyroid hormone treatment. Similar results were obtained in MG63 cells, whereas parathyroid hormone stimulation did not alter any of the parameters examined in dermal fibroblasts.

Conclusion:  These results indicate that human periodontal ligament cells respond to an intermittent parathyroid hormone exposure with changes in proliferation, differentiation and osteoprotegerin production in a maturation‐state dependent manner and therefore might be regulatorily involved in periodontal regeneration.
Moderate and Severe Erectile Dysfunction Equally Affects Life Satisfaction
Authors: Mallis Dimitrios , Moisidis Kyriakos , Kirana Paraskevi-Sofia , Papaharitou Stamatis , Simos Gregorios , Hatzichristou Dimitrios
Published: November 2005

Purpose

To explore the life satisfaction of patients with erectile dysfunction (ED) and to examine the relation between severity of ED and life satisfaction.

Materials and Methods

The study sample was recruited from patients who presented in an andrologic outpatient clinic complaining of ED. All patients underwent the basic clinical evaluation and were assessed by the International Index of Erectile Dysfunction (IIEF) and the Life Satisfaction Inventory (LSI).

Results

The study included 69 patients with ED (age range 22–71 years, mean 49.5, SD 13.7). The LSI appeared to have satisfactory internal consistency (Cronbach's alpha = 0.82). Men with ED had significantly lower satisfaction with their sexual life (t = −13.756, d.f. = 68, P = 0.000), but also significantly lower total score of satisfaction with their life (t = −2.793, d.f. = 68, P = 0.007) compared with available normative data from healthy population. However, when compared with controls, men with ED showed significantly higher satisfaction scores on their financial status (t = 5.075, d.f. = 68, P = 0.000) and on their leisure time activities (t = 4.029, d.f. = 68, P = 0.000). Regarding ED severity, mild ED affects patients’ satisfaction with sexual life less than do moderate and severe ED. Interestingly, no difference was identified between moderate and severe ED groups.

Conclusions

Men who seek help for ED have lower satisfaction with sexual life and lower satisfaction with their overall life compared with healthy people. Severity of ED seems to be an important factor, as men with moderate ED perceive the impact of ED on their life satisfaction equally with those with severe ED. ED patients gain more satisfaction from other domains of their life, provided they adopt coping behaviors that help compensate for their low overall life satisfaction. Furthermore, as ED patients do not differ from healthy people in their expressed subjective rating of quality of life (QoL), life satisfaction may be more sensitive than QoL assessment in the evaluation of the impact of ED on our patients’ life.
Comparative Seed Dispersal Effectiveness of Sympatric Alouatta guariba and Brachyteles arachnoides in Southeastern Brazil1
Authors: Martins Milene Moura
Published: November 2005

I compared the effectiveness of sympatric brown howlers (Alouatta guariba) and muriquis (Brachyteles arachnoides) as seed dispersers in terms of quantitative and qualitative attributes. I hypothesized that differences in feeding and behavioral patterns between these large‐bodied folivorous/frugivorous primates would lead to dissimilarities in their effectiveness as endozoochoric seed dispersal agents. The study was carried out in a semideciduous forest fragment of Fazenda Barreiro Rico, southeastern Brazil. Through behavioral sampling of frugivory and defecation events as well as analyses of fecal samples, I determined that A. guariba dispersed fewer species and produced a lower proportion of dung with intact seeds than B. arachnoides. There was no difference between the number of seeds in fecal samples of A. guariba and B. arachnoides. These primates affected to a similar degree both germination percentage and latency to germination of seeds they ingested or removed the pulp from. Howlers and muriquis were also similar in carrying seeds away from the parent trees. Contrary to muriquis, howlers defecated seeds under the canopy of conspecific lianas, where seeds are expected to suffer high mortality rates, and voided seeds predominantly in a clumped pattern. B. arachnoides was a more effective seed disperser when compared to A. guariba in some attributes evaluated, but not in others. Given the interspecific variation in recruitment patterns of tropical plants and the loss of frugivorous bird species at the study site, the differences between howlers and muriquis in their abilities as seed dispersers may crucially influence the composition and maintenance of seedling diversity.
A multiwavelength investigation of the temperature of the cold neutral medium
Authors: Roy Nirupam , Chengalur Jayaram N. , Srianand Raghunathan
Published: November 2005

We present measurements of the H i spin temperatures (Ts) of the cold neutral medium (CNM) towards radio sources that are closely aligned with stars for which published H2 ortho-para temperatures (T01) are available from ultraviolet (UV) observations. Our sample consists of 18 radio sources close to 16 nearby stars. The transverse separation of the lines of sight of the corresponding UV and radio observations varies from 0.1 to 12.0 pc at the distance of the star. The UV measurements do not have velocity information, so we use the velocities of low ionization species (e.g. Na i/K i/Ci) observed towards these same stars to make a plausible identification of the CNM corresponding to the H2 absorption. We then find that T01 and Ts match within observational uncertainties for lines of sight with H2 column density above 1015.8 cm−2, but deviate from each other below this threshold. This is consistent with the expectation that in the CNM Ts tracks the kinetic temperature due to collisions and that T01 is driven towards the kinetic temperature by proton exchange reactions.
Diffusive synchrotron radiation from extragalactic jets
Authors: Fleishman G. D.
Published: November 2005

Flattenings of non-thermal radiation spectra observed from knots and interknot locations of the jets of 3C 273 and M87 in the ultraviolet and X-ray bands are discussed within modern models of magnetic field generation in relativistic jets. Specifically, we explicitly take into account the effect of the small-scale random magnetic field, probably present in such jets, which gives rise to emission of diffusive synchrotron radiation, the spectrum of which deviates substantially from the standard synchrotron spectrum, especially at high frequencies. The calculated spectra agree well with the observed ones if the energy densities contained in small-scale and large-scale magnetic fields are comparable. The implications of this finding for magnetic field generation, particle acceleration and jet composition are discussed.
The Development of a Dual-Injection Hydrogen-Fueled Engine With High Power and High Efficiency
Authors: Kim Y. Y. , Lee Jong T. , Caton J. A.
Published: November 2005

To achieve high power and high efficiency in a hydrogen-fueled engine for all load conditions, the dual-injection hydrogen-fueled engine, which can derive the advantages of both high efficiency from external mixture hydrogen engine and high power from direct cylinder injection was developed. For verifying the feasibility of the above engine, a high-pressure hydrogen injector of ball-valve type and actuated by a solenoid was developed. A systematic experimental study was conducted by using a modified single-cylinder dual-injection hydrogen-fueled engine, which was equipped with both an intake injector and high-pressure in-cylinder injector. The results showed that (i) the developed high pressure hydrogen injector with a solenoid actuator had good gas tightness and fine control performance, (ii) the transient injection region, in which injection methods are changed from external fuel injection to direct-cylinder injection, ranged from 59 to 74% of the load, and (iii) the dual-injection hydrogen-fueled engine had the maximum torque of direct-cylinder fuel injection and the maximum efficiency of external fuel mixture hydrogen engines.
Influence of Operating Condition and Geometry on the Oil Film Thickness in Aeroengine Bearing Chambers
Authors: Gorse P. , Busam S. , Dullenkopf K.
Published: November 2005

Increasing the efficiency of modern jet engines does not only imply to the mainstream but also to the secondary air and oil system. Within the oil system the bearing chamber is one of the most challenging components. Oil films on the chamber walls are generated from oil droplets, ligaments, or film fragments, which emerge from bearings, seal plates and shafts, and enter the bearing chamber with an angular momentum. Furthermore, shear forces at its surface, gravity forces, and the design of scavenge and vent ports strongly impact the behavior of the liquid film. The present paper focuses on the experimental determination of the film thickness in various geometries of bearing chambers for a wide range of engine relevant conditions. Therefore, each configuration was equipped with five capacitive probes positioned at different circumferential locations. Two analytical approaches are used for a comprehensive discussion of the complex film flow.
Bayesian Network Approach for Gas Path Fault Diagnosis
Authors: Romessis C. , Mathioudakis K.
Published: November 2005

A method for solving the gas path analysis problem of jet engine diagnostics based on a probabilistic approach is presented. The method is materialized through the use of a Bayesian Belief Network (BBN). Building a BBN for gas turbine performance fault diagnosis requires information of a stochastic nature expressing the probability of whether a series of events occurred or not. This information can be extracted by a deterministic model and does not depend on hard to find flight data of different faulty operations of the engine. The diagnostic problem and the overall diagnostic procedure are first described. A detailed description of the way the diagnostic procedure is set-up, with focus on building the BBN from an engine performance model, follows. The case of a turbofan engine is used to evaluate the effectiveness of the method. Several simulated and benchmark fault case scenarios have been considered for this reason. The examined cases demonstrate that the proposed BBN-based diagnostic method composes a powerful tool. This work also shows that building a diagnostic tool, based on information provided by an engine performance model, is feasible and can be efficient as well.
Unsteady Aerodynamics of an Aeroengine Double Swirler Lean Premixing Prevaporizing Burner
Authors: Canepa Edward , Di Martino Pasquale , Formosa Piergiorgio , Ubaldi Marina , Zunino Pietro
Published: November 2005

Lean premixing prevaporizing (LPP) burners represent a promising solution for low-emission combustion in aeroengines. Since lean premixed combustion suffers from pressure and heat release fluctuations that can be triggered by unsteady large-scale flow structures, a deep knowledge of flow structures formation mechanisms in complex swirling flows is a necessary step in suppressing combustion instabilities. The present paper describes a detailed investigation of the unsteady aerodynamics of a large-scale model of a double swirler aeroengine LPP burner at isothermal conditions. A three-dimensional (3D) laser Doppler velocimeter and an ensemble-averaging technique have been employed to obtain a detailed time-resolved description of the periodically perturbed flow field at the mixing duct exit and associated Reynolds stress and vorticity distributions. Results show a swirling annular jet with an extended region of reverse flow near to the axis. The flow is dominated by a strong periodic perturbation, which occurs in all the three components of velocity. Radial velocity fluctuations cause important periodic displacement of the jet and the inner separated region in the meridional plane. The flow, as expected, is highly turbulent. The periodic stress components have the same order of magnitude of the Reynolds stress components. As a consequence the flow-mixing process is highly enhanced. Turbulence acts on a large spectrum of fluctuation frequencies, whereas the large-scale motion influences the whole flow field in an ordered way that can be dangerous for stability in reactive conditions.
Flow Characteristics and Stability Analysis of Variable-Density Rotating Flows in Compressor-Disk Cavities
Authors: Johnson Bruce V. , Lin J. D. , Daniels William A. , Paolillo Roger
Published: November 2005

Previous heat transfer experiments showed that significant differences in the flow and heat transfer characteristics can occur in models of aircraft gas-turbine, high-compressor drums. Experiments with heated disks and colder flow show large-scale instabilities that cause mixing between the cooling flow and the flow in the trapped cavities. The general result of this mixing is relatively high heat flux on the disks. Other heat transfer experiments, simulating the aircraft take-off condition with cold disks and hotter coolant, show decreased heat transfer due to the stabilizing effects of positive radial density gradients. A stability analysis for inviscid, variable-density flow was developed to quantify the effects of axial velocity, tangential velocity, and density profiles in the bore region of the disk cavities on the stabilizing or destabilizing characteristics of the flow. The criteria from the stability analysis were used to evaluate the axial velocity and density profile conditions required to stabilize three tangential-velocity profiles, obtained from previous experiments and analyses. The results from the parametric study showed that for Rossby numbers, the ratio of axial velocity to disk bore velocity, less than 0.1, the flow can be stabilized with ratios of cavity density to coolant density of less than 1.1. However, for Rossby numbers greater than 1, the flow in the bore region is unlikely to be stabilized with a positive radial density gradient. For Rossby numbers between 0.1 and 1.0, the flow stability is a more complex relationship between the velocity and density profiles. Results from the analysis can be used to guide the correlation of experimental heat transfer data for design systems.
Reduction of Power Losses in Bearing Chambers Using Porous Screens Surrounding a Ball Bearing
Authors: Flouros Michael
Published: November 2005

Trends in aircraft engine design have caused an increase in mechanical stress requirements for rolling bearings. Consequently, a high amount of heat is rejected, which results in high oil scavenge temperatures. An RB199 turbofan bearing and its associated chamber were modified to carry out a survey aiming to reduce power losses in bearing chambers. The test bearing was a 124 mm PCD ball bearing with a split inner ring employing under-race lubrication by two individual jets. The survey was carried out in two parts. In the first part, the investigations were focused on the impact on the power losses in the bearing chamber of the operating parameters, such as oil flow, oil temperature, sealing air flow, bearing chamber pressure, and shaft speed. In the second part, the investigations focused on the reduction of the dwell time of the air and oil mixture in the bearing compartment and its impact on the power losses. In this part, porous screens were introduced around the bearing. These screens would aid the oil to flow out of the compartment and reduce droplet-droplet interactions as well as droplet-bearing chamber wall interactions. The performance of the screens was evaluated by torque measurements. A high-speed camera was used to visualize the flow in the chamber. Considerable reduction in power loss was achieved. This work is part of the European Research programme GROWTH ATOS (Advanced Transmission and Oil Systems).
An Integrated Fault Diagnostics Model Using Genetic Algorithm and Neural Networks
Authors: Sampath Suresh , Singh Riti
Published: November 2005

This paper presents the development of an integrated fault diagnostics model for identifying shifts in component performance and sensor faults using the Genetic Algorithm and Artificial Neural Network. The diagnostics model operates in two distinct stages. The first stage uses response surfaces for computing objective functions to increase the exploration potential of the search space while easing the computational burden. The second stage uses the concept of a hybrid diagnostics model in which a nested neural network is used with genetic algorithm to form a hybrid diagnostics model. The nested neural network functions as a pre-processor or filter to reduce the number of fault classes to be explored by the genetic algorithm based diagnostics model. The hybrid model improves the accuracy, reliability, and consistency of the results obtained. In addition significant improvements in the total run time have also been observed. The advanced cycle Intercooled Recuperated WR21 engine has been used as the test engine for implementing the diagnostics model.
Adjoint Harmonic Sensitivities for Forced Response Minimization
Authors: Duta Mihai C. , Campobasso Michelle S. , Giles Michael B. , Lapworth Leigh B.
Published: November 2005

This paper presents an adjoint analysis for three-dimensional unsteady viscous flows aimed at the calculation of linear worksum sensitivities involved in turbomachinery forced response predictions. The worksum values are normally obtained from linear harmonic flow calculations but can also be computed using the solution to the adjoint of the linear harmonic flow equations. The adjoint method has a clear advantage over the linear approach if used within a rotor forced vibration minimization procedure which requires the structural response to a large number of different flow excitation sources characterized by a unique frequency and interblade phase angle. Whereas the linear approach requires a number of linear flow calculations at least equal to the number of excitation sources, the adjoint method reduces this cost to a single adjoint solution for each structural mode of rotor response. A practical example is given to illustrate the dramatic computational saving associated with the adjoint approach.
Towards Modeling Lean Blow Out in Gas Turbine Flameholder Applications
Authors: Kim Won-Wook , Lienau Jeffrey J. , Van Slooten Paul R. , Colket Meredith B. , Malecki Robert E. , Syed Saadat
Published: November 2005

The objective of this study was to assess the accuracy of the large-eddy simulation (LES) methodology, with a simple combustion closure based on equilibrium chemistry, for simulating turbulent reacting flows behind a bluff body flameholder. Specifically, the variation in recirculation zone length with change in equivalence ratio was calculated and compared to experimental measurements. It was found that the present LES modeling approach can reproduce this variation accurately. However, it understated the recirculation zone length at the stoichiometric condition. The approach was assessed at the lean blow out condition to evaluate its behavior at the lean limit and to analyze the physics of combustion instability.
Validation of CESI Blade Life Management System by Case Histories and in situ NDT
Authors: Rinaldi Claudia , Bicego Valerio , Colombo Pier Paolo
Published: November 2005

A life management system was developed for hot components of large industrial gas turbines, in the form of a software tool for predicting component lives under typical operational transients (normal and also abnormal) and steady-state periods. The method utilizes results of previous thermo-mechanical finite element and finite volume fluid mechanics analyses. The basic idea of this method is using data from structural and aero-thermal analyses (pressures and temperatures), blade life theory, and material properties as an input to algorithms, and using operational and historical data to validate the predicted damage amounts. The software developed in this project, of general applicability to all GT models, has been implemented with reference to the geometries, materials, and service conditions of a Fiat-Westinghouse model.
Role of Silver Ions in Destabilization of Intermolecular Adhesion Forces Measured by Atomic Force Microscopy in
Staphylococcus epidermidis
Biofilms
Authors: Chaw K. C. , Manimaran M. , Tay Francis E. H.
Published: November 2005

In this paper, we report on the potential use of atomic force microscopy (AFM) as a tool to measure the intermolecular forces in biofilm structures and to study the effect of silver ions on sessile
Staphylococcus epidermidis
cell viability and stability. We propose a strategy of destabilizing the biofilm matrix by reducing the intermolecular forces within the extracellular polymeric substances (EPSs) using a low concentration (50 ppb) of silver ions. Our AFM studies on the intermolecular forces within the EPSs of
S. epidermidis
RP62A and
S
.
epidermidis
1457 biofilms suggest that the silver ions can destabilize the biofilm matrix by binding to electron donor groups of the biological molecules. This leads to reductions in the number of binding sites for hydrogen bonds and electrostatic and hydrophobic interactions and, hence, the destabilization of the biofilm structure.
New Reporter Cell Line To Evaluate the Sequential Emergence of Multiple Human Cytomegalovirus Mutations during In Vitro Drug Exposure
Authors: Gilbert C. , Boivin G.
Published: November 2005

We developed a new reporter cell line for human cytomegalovirus (HCMV) drug susceptibility testing. This cell line was obtained by incorporating the luciferase reporter gene under the control of an HCMV-specific promoter into the genome of astrocytoma cells (U373MG). We then used our reporter cell line to evaluate phenotypic changes conferred by the sequential emergence of HCMV UL54 and UL97 mutations following long-term drug exposure. The laboratory strain AD169 was passaged in the presence of increasing concentrations of ganciclovir (one viral line) or foscarnet (two viral lines). Resistant viruses were plaque purified at five different concentrations of ganciclovir and at three different concentrations of foscarnet. In addition to the previously described M460I and L595S UL97 mutations and the L545S and V812L UL54 mutations, exposition to ganciclovir (up to 3,000 μM) resulted in the selection of two unreported UL54 mutations (P829S and D879G). Passages in the presence of foscarnet (up to 3,000 μM) resulted in the selection of seven not previously described UL54 mutations (K500N, T552N, S585A, N757K, L802V, L926V, and L957F) in addition to the N408D mutation that has been associated with ganciclovir and cidofovir resistance. Long-term exposure of HCMV to either ganciclovir or foscarnet ultimately resulted in the selection of multiple UL54 mutations that conferred high levels of resistance to all approved HCMV DNA polymerase inhibitors, i.e., ganciclovir, cidofovir, and foscarnet. Emergence of each viral mutation conferred stepwise increases in drug 50% inhibitory concentrations that could be objectively measured with the new reporter cell assay.
Inhibition of Human Immunodeficiency Virus Type 1 Reverse Transcriptase, RNase H, and Integrase Activities by Hydroxytropolones
Authors: Didierjean Joël , Isel Catherine , Querré Flore , Mouscadet Jean-François , Aubertin Anne-Marie , Valnot Jean-Yves , Piettre Serge R. , Marquet Roland
Published: November 2005

Human immunodeficiency virus type I reverse transcriptase (RT) possesses distinct DNA polymerase and RNase H sites, whereas integrase (IN) uses the same active site to perform 3′-end processing and strand transfer of the proviral DNA. These four enzymatic activities are essential for viral replication and require metal ions. Two Mg
2+
ions are present in the RT polymerase site, and one or two Mg
2+
ions are required for the catalytic activities of RNase H and IN. We tested the possibility of inhibition of the RT polymerase and RNase H as well as the IN 3′-end processing and transfer activities of purified enzymes by a series of 3,7-dihydroxytropolones designed to target two Mg
2+
ions separated by ∼3.7 Å. The RT polymerase and IN 3′ processing and strand transfer activities were inhibited at submicromolar concentrations, while the RNase H activity was inhibited in the low micromolar range. In all cases, the lack of inhibition by tropolones and O-methylated 3,7-dihydroxytropolones was consistent with the active molecules binding the metal ions in the active site. In addition, inhibition of the DNA polymerase activity was shown to depend on the Mg
2+
concentration. Furthermore, selective inhibitors were identified for several of the activities tested, leaving some potential for design of improved inhibitors. However, all tested compounds exhibited cellular toxicity that presently limits their applications.
Treatment of
Candida glabrata
Infection in Immunosuppressed Mice by Using a Combination of Liposomal Amphotericin B with Caspofungin or Micafungin
Authors: Olson Jon A. , Adler-Moore Jill P. , Smith P. J. , Proffitt Richard T.
Published: November 2005

While
Candida albicans
remains the most common
Candida
isolate,
Candida glabrata
accounts for approximately 15 to 20% of all
Candida
infections in the United States. In this study we used immunosuppressed mice infected with
C. glabrata
to investigate the efficacy of liposomal amphotericin B alone or in combination with the echinocandin caspofungin or micafungin. For monotherapy, mice were given six daily doses of liposomal amphotericin B (3 to 20 mg/kg of body weight), caspofungin (1 to 5 mg/kg), or micafungin (2.5 to 10 mg/kg). With concomitant therapy, mice received liposomal amphotericin B (7.5 mg/kg) in addition to caspofungin (2.5 mg/kg) or micafungin (2.5 mg/kg) for 6 days. For sequential therapy, liposomal amphotericin B was administered on days 1 to 3 and caspofungin or micafungin was given on days 4 to 6; conversely, caspofungin or micafungin was administered on days 1 to 3 and liposomal amphotericin B was given on days 4 to 6. Efficacy was based on the number of CFU per gram of kidney 21 days postchallenge. Monotherapy with liposomal amphotericin B (7.5 to 20 mg/kg) was significantly more effective than no drug treatment (control group) (
P
< 0.05) and demonstrated a dose-dependent response, with 20 mg/kg lowering the CFU/g from 6.3 to 4.2 (significantly different from the value for the control group [
P
< 0.001]). Monotherapy with all echinocandin doses lowered the CFU/g from 6.0 to 6.4 to 2.7 to 3.3 (significantly different from the value for the control group [
P
< 0.001]) with no dose-dependent response. Complete clearance of infection could be achieved only when liposomal amphotericin B was given either concomitantly with caspofungin or micafungin or if liposomal amphotericin B was given sequentially with caspofungin. In conclusion, the combination of liposomal amphotericin B with an echinocandin markedly improved the therapeutic outcome in murine
C. glabrata
systemic infection.
Optimization of Meropenem Minimum Concentration/MIC Ratio To Suppress In Vitro Resistance of
Pseudomonas aeruginosa
Authors: Tam Vincent H. , Schilling Amy N. , Neshat Shadi , Poole Keith , Melnick David A. , Coyle Elizabeth A.
Published: November 2005

Suppression of resistance in a dense
Pseudomonas aeruginosa
population has previously been shown with optimized quinolone exposures. However, the relevance to β-lactams is unknown. We investigated the bactericidal activity of meropenem and its propensity to suppress
P. aeruginosa
resistance in an in vitro hollow-fiber infection model (HFIM). Two isogenic strains of
P. aeruginosa
(wild type and an AmpC stably derepressed mutant [MIC = 1 mg/liter]) were used. An HFIM inoculated with approximately 1 × 10
8
CFU/ml of bacteria was subjected to various meropenem exposures. Maintenance doses were given every 8 h to simulate the maximum concentration achieved after a 1-g dose in all regimens, but escalating unbound minimum concentrations (
C
mi
n
s) were simulated with different clearances. Serial samples were obtained over 5 days to quantify the meropenem concentrations, the total bacterial population, and subpopulations with reduced susceptibilities to meropenem (>3× the MIC). For both strains, a significant bacterial burden reduction was seen with all regimens at 24 h. Regrowth was apparent after 3 days, with the
C
min
/MIC ratio being ≤1.7 (time above the MIC, 100%). Selective amplification of subpopulations with reduced susceptibilities to meropenem was suppressed with a
C
min
/MIC of ≥6.2 or by adding tobramycin to meropenem (
C
min
/MIC = 1.7). Investigations that were longer than 24 h and that used high inocula may be necessary to fully evaluate the relationship between drug exposures and the likelihood of resistance suppression. These results suggest that the
C
min
/MIC of meropenem can be optimized to suppress the emergence of non-plasmid-mediated
P. aeruginosa
resistance. Our in vitro data support the use of an extended duration of meropenem infusion for the treatment of severe nosocomial infections in combination with an aminoglycoside.
Antimalarial Activities of New Pyrrolo[3,2-f]Quinazoline-1,3-Diamine Derivatives
Authors: Guan Jian , Zhang Quan , O'Neil Michael , Obaldia Nicanor , Ager Arba , Gerena Lucia , Lin Ai J.
Published: November 2005

WR227825 is an antimalarial pyrroloquinazolinediamine derivative with a high potency but a low therapeutic index. A series of carbamate, carboxamide, succinimide, and alkylamine derivatives of WR227825 were prepared to search for compounds with an improved therapeutic index. The new acetamides and imide showed potent cell growth inhibition against four clones of
Plasmodium falciparum
(D-6, RCS, W-2, and TM91C235), with a 50% inhibitory concentration of ∼0.01 ng/ml, and were highly active against
Plasmodium berghei
, with 100% cure at doses from <0.1 mg/kg of body weight to 220 mg/kg. The carbamates and alkyl derivatives, however, showed weak activity against
Plasmodium falciparum
cell growth but were highly efficacious in tests against
P. berghei
by the Thompson test. The best compounds, bis-ethylcarbamate (compound 2a) and tetra-acetamide (3a) derivatives, further demonstrated high potency against the sporozoite
Plasmodium yoelii
in mice and
P. falciparum
and
Plasmodium vivax
in aotus monkeys. Against the AMRU-1 strain of
P. vivax
, which has four dihydrofolate reductase mutations and is highly resistant to antifolates, tetra-acetamide 3a cured the monkeys at doses of 1 and 3 mg/kg. Compound 2a cured only one out of two monkeys at 3 mg/kg. The results indicated that the new derivatives 2a and 3a not only have retained/improved the antimalarial efficacy of the parent compound WR227825 but also were less toxic to the animals used in the tests.
Antimicrobial Activities and Structures of Two Linear Cationic Peptide Families with Various Amphipathic β-Sheet and α-Helical Potentials
Authors: Jin Yi , Hammer Janet , Pate Michelle , Zhang Yu , Zhu Fang , Zmuda Erik , Blazyk Jack
Published: November 2005

Many naturally occurring antimicrobial peptides comprise cationic linear sequences with the potential to adopt an amphipathic α-helical conformation. We designed a linear 18-residue peptide that adopted an amphipathic β-sheet structure when it was bound to lipids. In comparison to a 21-residue amphipathic α-helical peptide of equal charge and hydrophobicity, this peptide possessed more similar antimicrobial activity and greater selectivity in binding to and inducing leakage in vesicles composed of bacterial membrane lipids than vesicles composed of mammalian membrane lipids (J. Blazyk, R. Weigand, J. Klein, J. Hammer, R. M. Epand, R. F. Epand, W. L. Maloy, and U. P. Kari, J. Biol. Chem. 276:27899-27906, 2001). Here, we compare two systematically designed families of linear cationic peptides to evaluate the importance of amphipathicity for determination of antimicrobial activity. Each peptide contains six lysine residues and is amidated at the carboxyl terminus. The first family consists of five peptides with various capacities to form amphipathic β-sheet structures. The second family consists of six peptides with various potentials to form amphipathic α helices. Only those peptides that can form a highly amphipathic structure (either a β sheet or an α helix) possessed significant antimicrobial activities. Striking differences in the abilities to bind to and induce leakage in membranes and lipid vesicles were observed for the two families. Overall, the amphipathic β-sheet peptides are less lytic than their amphipathic α-helical counterparts, particularly toward membranes containing phosphatidylcholine, a lipid commonly found in mammalian plasma membranes. Thus, it appears that antimicrobial peptides that can form an amphipathic β-sheet conformation may offer a selective advantage in targeting bacterial cells.
Comparison of the Fungicidal Activities of Caspofungin and Amphotericin B against
Candida glabrata
Authors: Barchiesi Francesco , Spreghini Elisabetta , Tomassetti Serena , Arzeni Daniela , Giannini Daniele , Scalise Giorgio
Published: November 2005

We investigated the fungicidal activity of caspofungin (CAS) and amphotericin B (AMB) against 16 clinical isolates of
Candida glabrata
. The minimum fungicidal concentrations (MFCs) of CAS were similar to those of AMB, ranging from 2.0 to >8.0 μg/ml. Time-kill assays performed on selected isolates showed that AMB was fungicidal at concentrations four times the MIC while CAS was not. A neutropenic-mouse model of disseminated infection was utilized to determine the residual fungal kidney burden. While doses as low as 0.3 and 1 mg/kg of body weight/day of CAS and AMB, respectively, were effective at reducing the counts with respect to controls, organ sterilization was reached when both drugs were administered at 5 mg/kg/day. Our study reveals that, similar to AMB, CAS has the potential for a fungicidal effect in vivo against this difficult-to-treat fungal pathogen.
Molecular Characterization of Pneumococci with Efflux-Mediated Erythromycin Resistance and Identification of a Novel
mef
Gene Subclass,
mef
(I)
Authors: Cochetti Ileana , Vecchi Manuela , Mingoia Marina , Tili Emily , Catania Maria R. , Manzin Aldo , Varaldo Pietro E. , Montanari Maria Pia
Published: November 2005

The molecular genetics of macrolide resistance were analyzed in 49 clinical pneumococci (including an “atypical” bile-insoluble strain currently assigned to the new species
Streptococcus pseudopneumoniae
) with efflux-mediated erythromycin resistance (M phenotype). All test strains had the
mef
gene, identified as
mef
(A) in 30 isolates and
mef
(E) in 19 isolates (including the
S. pseudopneumoniae
strain) on the basis of PCR-restriction fragment length polymorphism analysis. Twenty-eight of the 30
mef
(A) isolates shared a pulsed-field gel electrophoresis (PFGE) type corresponding to the England
14
-9 clone. Of those isolates, 27 (20 belonging to serotype 14) yielded multilocus sequence type ST9, and one isolate yielded a new sequence type. The remaining two
mef
(A) isolates had different PFGE types and yielded an ST9 type and a new sequence type. Far greater heterogeneity was displayed by the 19
mef
(E) isolates, which fell into 11 PFGE types, 12 serotypes (though not serotype 14), and 12 sequence types (including two new ones and an undetermined type for the
S. pseudopneumoniae
strain). In all
mef
(A) pneumococci, the
mef
element was a regular Tn
1207.1
transposon, whereas of the
mef
(E) isolates, 17 carried the mega element and 2 exhibited a previously unreported organization, with no PCR evidence of the other open reading frames of mega. The
mef
gene of these two isolates, which did not match with the
mef
(E) gene of the mega element (93.6% homology) and which exhibited comparable homology (91.4%) to the
mef
(A) gene of the Tn
1207.1
transposon, was identified as a novel
mef
gene variant and was designated
mef
(I). While penicillin-nonsusceptible isolates (three resistant isolates and one intermediate isolate) were all
mef
(E) strains, tetracycline resistance was also detected in three
mef
(A) isolates, due to the
tet
(M) gene carried by a Tn
916
-like transposon. A similar mechanism accounted for resistance in four of the five tetracycline-resistant isolates carrying
mef
(E), in three of which mega was inserted in the Tn
916
-like transposon, giving rise to the composite element Tn
2009
. In the fifth
mef
(E)-positive tetracycline-resistant isolate (the
S. pseudopneumoniae
strain), tetracycline resistance was due to the presence of the
tet
(O) gene, apparently unlinked to
mef
(E).