bluuebunny/crossref_metadata_2025 huggingface dataset:
The Conditional Analysis of Dispositions and the Intrinsic Dispositions Thesis
Authors: CHOI SUNGHO
Published: April 2009

The idea that dispositions are an intrinsic matter has been popular among contemporary philosophers of dispositions. In this paper I will first state this idea as exactly as possible. I will then examine whether it poses any threat to the two current versions of the conditional analysis of dispositions, namely, the simple and reformed conditional analysis of dispositions. The upshot is that the intrinsic nature of dispositions, when properly understood, doesn’t spell trouble for either of the two versions of the conditional analysis of dispositions. Along the way, I will propose an extensionally correct and practically useful criterion for identifying nomically intrinsic dispositions and criticize one objection raised by Lewis against the simple conditional analysis of dispositions.
Refined Wave-Based Control Applied to Nonlinear, Bending, and Slewing Flexible Systems
Authors: O’Connor William J. , Fumagalli Alessandro
Published: April 2009

The problem of controlling the position and vibration of open-chain flexible structures undergoing fast maneuvers is of wide interest. In this work, the general flexible structure is actuated by a single actuator at one end, which, depending on the case of interest, is capable of rotating, translating, or simultaneously translating and rotating the root of the flexible system. The goal is to control the motion of the entire flexible system from rest to rest. This needs a simultaneous synthesis of position control and active vibration damping. A new strategy is presented based on further developments of wave-based control. As before it views the actuator motion as simultaneously launching and absorbing mechanical waves into and out of the system. But a new simple method of resolving the actuator motion into two waves is presented. By measuring the elastic forces exchanged at the interface between the actuator and the rest of the system, a returning displacement wave can be resolved. This is then added to a set, launch wave to determine the actuator motion. Typically the launch wave is set to reach half the target displacement, and the addition of the return wave absorbs the vibration while simultaneously moving the system the second half of the target displacement, neatly achieving the two goals in one controlled motion. To date wave-based control has been applied to lumped, second-order, longitudinally vibrating systems. The refined method avoids a difficulty that previously arose in some contexts, thereby making wave-based control even more generic. It can easily control nonlinear elastic systems, laterally bending systems (in the sense of Euler–Bernoulli beams), and slewing systems where lateral translation and system rotation are strongly coupled. Numerical simulation results are presented for controlled, rest-to-rest maneuvers of representative flexible structures, all controlled using the same (linear) algorithm. The first case is control of a string of rigid bodies interconnected by nonlinear springs. The second problem is the rotational control of a very flexible one-link planar manipulator. Finally, in an extension of the previous system, the actuator both translates and rotates, slewing the flexible system to a target lateral displacement and a target rotation angle simultaneously. The strategy is found to be remarkably effective with many advantages. It seamlessly integrates position and vibration control. It is rapid, robust, energy efficient, and computationally light. It requires little sensing, little knowledge of the flexible system dynamics, and copes well with nonideal actuator behavior. It is generic and easily handles a wide variety of flexible systems. It can get the entire system to stop dead exactly at target with little vibration in transit.
Delamination Susceptibility of Coatings Under High Thermal Flux
Authors: Xue Z. , Evans A. G. , Hutchinson J. W.
Published: April 2009

Delamination of coatings initiated by small cracks paralleling the free surface is investigated under conditions of high thermal flux associated with a through-thickness temperature gradient. A crack disrupts the heat flow thereby inducing crack tip stress intensities that can become critical. A complete parametric dependence of the energy release rate and mode mix is presented in terms of the ratio of the crack length to its depth below the surface and coefficients characterizing heat transfer across the crack and across the gaseous boundary layer between the surface and the hot gas. Proximity to the surface elevates the local temperature, which in turn, may significantly increase the crack driving force. A detailed assessment reveals that the energy release rates induced by high heat flux are capable of extending subsurface delaminations in thermal barrier coatings, but only when the modulus has been elevated by either calcium-magnesium-alumino-silicate (CMAS) penetration or sintering. Otherwise, the energy release rate remains well below the toughness.
Dynamic Stability Analysis of Stiffened Shell Panels With Cutouts
Authors: Patel S. N. , Datta P. K. , Sheikh A. H.
Published: April 2009

A finite element dynamic instability analysis of stiffened shell panels with cutout subjected to uniform in-plane harmonic edge loading along the two opposite edges is presented in this paper. The eight-noded isoparametric degenerated shell element and a compatible three-noded curved beam element are used to model the shell panels and the stiffeners, respectively. As the usual formulation of degenerated beam element is found to overestimate the torsional rigidity, an attempt has been made to reformulate it in an efficient manner. Moreover the new formulation for the beam element requires five degrees of freedom per node as that of shell element. Bolotin method is applied to analyze the dynamic instability regions. Numerical results of convergence studies are presented and comparison is made with the published results from literature. The effects of various parameters such as shell geometry, radius of curvature, cutout size, stiffening scheme, and dynamic load factors are considered in dynamic instability analysis of stiffened shell panels with cutout. The free vibration and static stability (buckling) results are also presented. With the consideration of radius of curvatures the panels reduce from deep shell case to shallow shell case and finally become flat plate.
Nonlinear Field Theory of Fracture Mechanics for Paramagnetic and Ferromagnetic Materials
Authors: Chen Xiaohong
Published: April 2009

A nonlinear field theory of fracture mechanics is developed for crack propagation in paramagnetic and ferromagnetic materials from the global energy balance equation and the non-negative global dissipation requirement. The crack-front generalized J̃-integral is equivalent to the generalized energy release rate serving as the thermodynamic driving force for crack propagation and also related to the generalized energy-momentum tensor in a way similar to the material force method. On the basis of the developed theory, the generalized energy release rate method, the generalized J̃-integral method, and the extended essential work of fracture method are proposed for quasistatic and dynamic fracture characterization of magnetosensitive materials in the presence of magnetothermomechanical coupling and dissipative effects. The present work overcomes the drawbacks and limitations of conventional fracture mechanics and resolves the controversial issues on magnetoelastic fracture criterion. Especially, the crack-front generalized J̃-integral has an odd dependence on the magnetic induction intensity factor for a Griffith-type crack in a magnetoelastic solid.
Fabrication and Bioconjugation of Micro- and Nanoscale Structures Intended for Cancer-Specific Antigen Detection
Authors: Klein Kevin M. , Ostrowicki Gregory , Gewirtz Andrew T. , Sitaraman Suresh K.
Published: April 2009

Cleanroom processes can be used for fabricating microscale and nanoscale structures, and such structures, when bioconjugated, can be used for detecting low levels of cancer-specific circulating antigens. The concentration of such circulating antigens in human serum continues to increase with cancer progression, and therefore, detection of cancer at very early stages of the disease can be facilitated by monitoring small increases in circulating antigen concentration. Therefore, fabrication and bioconjugation are the first steps in the development of bio-assays for cancer detection. In this work, microscale and nanoscale Au/Cr thin film structures have been fabricated on Si substrate using dc sputtering and electron-beam (e-beam) evaporation in combination with photo and e-beam lithography. Using the fabricated device material stack (Au/Cr/Si), we have assessed the binding affinity of Au, Cr, and Si with Protein G, and antibodies for prostate specific antigen and cancer antigen 125, an ovarian cancer-associated antigen. Based on our experiments, we see that the thin gold layer of the Au/Cr/Si samples provides increased biomaterial binding affinity, and the chromium layer has a similar, if not less, binding affinity compared with the silicon chip alone. Thus, this work demonstrates that the fabricated material stack provides an appropriate platform for antigen detection.
A Novel Projection Moiré System for Measuring PWBA Warpage Using Simulated Optimized Convective Reflow Process
Authors: Powell Reinhard E. , Ume I. Charles
Published: April 2009

The shadow moiré technique is a widely used method of measuring printed wiring board (PWB) warpage. It has a high resolution, high accuracy, and is suitable for use in an online environment. The shortcoming of the shadow moiré technique is that it cannot be used to measure PWBs populated with chip packages. In this paper, a novel warpage measurement system based on the projection moiré technique is presented. The system can be used to measure bare PWBs, as well as PWBs populated with chip packages. In order to use the projection moiré system to accurately determine the warpage of PWBs and chip packages separately, an automated chip package detection algorithm based on active contours is utilized. Unlike the shadow moiré technique, which uses a glass grating, the projection moiré technique uses a virtual grating. The virtual grating sizes can be adjusted, making it versatile for measuring various PWB and chip package sizes. Without the glass grating, which is a substantial heat inertia, the PWB/printed wiring board assembly (PWBA) sample can be heated more evenly during the thermal process. The projection moiré system described in this paper can also be used to measure the warpage of PWBs/PWBAs/chip packages during convective reflow processes. In this paper, the characteristics of the projection moiré warpage measurement system will be described. In addition, the system will be used to measure the warpage of a PWB and plastic ball grid array packages during a Lee optimized convective reflow process (Lee, N.-C., 2002, Reflow Soldering Processes and Troubleshooting SMT, BGA, CSP, and Flip Chip Technologies, Butterworth-Heinemann, MA). It is concluded that this projection moiré warpage measurement system is a powerful tool to study the warpage of populated PWBs during convective reflow processes.
Analysis of Heat Transfer Enhancement in Minichannel Heat Sinks With Turbulent Flow Using H2O–Al2O3 Nanofluids
Authors: Bergman T. L.
Published: April 2009

Heat transfer enhancement associated with use of a nanofluid coolant is analyzed for small electronic heat sinks. The analysis is based on the ε-NTU heat exchanger methodology, and is used to examine enhancement associated with use of H2O–Al2O3 nanofluids in a heat sink experiencing turbulent flow. Predictive correlations are generated to ascertain the degree of enhancement based on the fluid’s thermophysical properties. The enhancement is quite small, suggesting the limited usefulness of nanofluids in this particular application.
Experimental Study of Water Liquid-Vapor Two-Phase Pressure Drop Across an Array of Staggered Micropin-Fins
Authors: Konishi Christopher A. , Qu Weilin , Pfefferkorn Frank E.
Published: April 2009

This study concerns pressure drop of adiabatic water liquid-vapor two-phase flow across an array of 1950 staggered square micropin-fins having a 200×200 μm cross section by 670 μm height. The ratios of longitudinal pitch and transverse pitch to pin-fin equivalent diameter are equal to 2. An inline immersion heater upstream of the micropin-fin test module was employed to produce liquid-vapor two-phase mixture, which flowed across the micropin-fin array. The test module was well insulated to maintain adiabatic condition. Four maximum mass velocities of 184 kg/m2 s, 235 kg/m2 s, 337 kg/m2 s, and 391 kg/m2 s, and a range of vapor qualities for each maximum mass velocity were tested. Measured pressure drop increases drastically with increasing vapor quality. Nine existing two-phase pressure drop models and correlations were assessed. The Lockhart–Martinelli correlation for laminar liquid-laminar vapor combination in conjunction with a single-phase friction factor correlation proposed for the present micropin-fin array provided the best agreement with the data.
The Energy Absorption Characteristics of Square Mild Steel Tubes With Multiple Induced Circular Hole Discontinuities—Part I: Experiments
Authors: Bodlani S. B. , Yuen S. Chung Kim , Nurick G. N.
Published: April 2009

This two-part article reports the results of experimental and numerical works conducted on the energy absorption characteristics of thin-walled square tubes with multiple circular hole discontinuities. Part I presents the experimental tests in which dynamic and quasistatic axial crushings are performed. The mild steel tubes are 350 mm in length, 50 mm wide, and 1.5 mm thick. Circular hole discontinuities, 17 mm in diameter, are laterally drilled on two or all four opposing walls of the tube to form opposing hole pairs. The total number of holes varies from 2 to 10. The results indicate that the introduction of holes decreases the initial peak force but an increase in the number of holes beyond 2 holes per side does not further significantly decrease the initial peak force. The findings show that strategic positioning of holes triggers progressive collapse hence improving energy absorption. The results also indicate that the presence of holes may at times disrupt the formation of lobes thus compromising the energy absorption capacity of the tube. In Part II, the finite element package ABAQUS/EXPLICIT version 6.4–6 is used to model the dynamic axial crushing of the tubes and to investigate the action of the holes during dynamic loading at an impact velocity of 8 m/s.
Design and evaluation of a methodology to perform personalized visual biofeedback for reducing respiratory amplitude in radiation treatment
Authors: Masselli Grazia Maria Pia , Silvestri Sergio , Ramella Sara , Trodella Lucio
Published: April 2009

A methodology to perform personalized visual biofeedback aimed to the reduction of respiratory amplitude is here proposed. A custom‐made software allows to adapt the biofeedback parameters to a patient's respiratory pattern by calculating a limiting range for respiratory amplitude obtained from data acquired during free breathing. The proposed methodology has been tested on ten healthy volunteers and on five lung cancer patients undergoing radiotherapy treatment. The protocol for volunteers consisted of 3 min of data acquisition during the subject's free breathing, 2 min of visual biofeedback within the limits, and 3 min of free breathing. The patients’ free breathing was acquired in 3 min and the visual biofeedback performed during all the sessions of the radiotherapy treatment, i.e., an average of eight sessions and an average total treatment time of 2000 s each patient. All the volunteers and three patients of the five found the protocol comfortable. The settlement time needed for considering the limiting range stabilized during free breathing has been calculated as . During visual biofeedback the baseline shift was removed and the average respiratory amplitude was reduced by about 40% for all the subjects. The variability of the breathing amplitude remained unaltered during biofeedback. Eight volunteers and three patients remained within the limiting range for more than 90% of the biofeedback period; all subjects remained within the limiting range for more than 80% of the biofeedback period. During the biofeedback period both groups, volunteers and patients, showed a significant increase in breathing frequency which was mostly doubled. Patients with shallow breathing performed comfortably the biofeedback.
Solid Water as phantom material for dosimetry of electron backscatter using low‐energy electron beams: A Monte Carlo evaluation
Authors: Chow James C. L. , Owrangi Amir M.
Published: April 2009

This study evaluated the dosimetry of electron backscatter when Solid Water is used to substitute water as phantom in electron radiotherapy. Monte Carlo simulation (EGSnrc‐based code) was employed to predict electron energy spectra and depth doses for the 0.5 and of Solid Water and water slabs above of lead (Pb) layers using electron beams with energies of 4 and . For comparison, Monte Carlo simulations were repeated with Pb layers taken out from the phantoms using the same experimental configuration. Analyses on electron energy spectra for the 4 and electron beams showed that deviations of electron energy distributions between the Solid Water and water phantom were more significant in the high‐energy range (i.e., close to the maximal electron energy) than the lower range corresponding to the electron backscatter. These deviations of electron energy spectra varied with depth and were mainly due to the electron fluence or beam attenuation. Dosimetry results from Monte Carlo simulations showed that the Solid Water phantom had lower depth dose compared to water with the same experimental setup. For the electron beams with of Solid Water, depth doses were 1.8%–3.9% and 2.3%–4.4% lower than those in water, with and without the Pb layer underneath, respectively. Thicker Solid Water of resulted in different decreases in depth doses of 1.8%–4.6% (with Pb) and 2.3%–4.4% (without Pb) compared to water. For higher nominal electron beam energy of with of Solid Water, depth doses decreased 1.7%–2.9% (with Pb) and 1.6%–2.1% (without Pb) compared to water. These decreases in depth doses changed to 1.7%–3.7% (with Pb) and 1.7%–3% (without Pb) when the thickness of Solid Water was increased to . The dosimetry data in this study are useful in determining the correction factor when using Solid Water to substitute water for the electron backscatter measurement in electron radiotherapy.
Monte Carlo evaluation of the convolution/superposition algorithm of Hi‐Art™ tomotherapy in heterogeneous phantoms and clinical cases
Authors: Sterpin E. , Salvat F. , Olivera G. , Vynckier S.
Published: April 2009

The reliability of the convolution/superposition (C/S) algorithm of the Hi‐Art™ tomotherapy system is evaluated by using the Monte Carlo model TomoPen, which has been already validated for homogeneous phantoms. The study was performed in three stages. First, measurements with EBT Gafchromic film for a field in a heterogeneous phantom consisting of two slabs of polystyrene separated with Styrofoam were compared to simulation results from TomoPen. The excellent agreement found in this comparison justifies the use of TomoPen as the reference for the remaining parts of this work. Second, to allow analysis and interpretation of the results in clinical cases, dose distributions calculated with TomoPen and C/S were compared for a similar phantom geometry, with multiple slabs of various densities. Even in conditions of lack of lateral electronic equilibrium, overall good agreement was obtained between C/S and TomoPen results, with deviations within 3%/2 mm, showing that the C/S algorithm accounts for modifications in secondary electron transport due to the presence of a low density medium. Finally, calculations were performed with TomoPen and C/S of dose distributions in various clinical cases, from large bilateral head and neck tumors to small lung tumors with diameter of . To ensure a “fair” comparison, identical dose calculation grid and dose‐volume histogram calculator were used. Very good agreement was obtained for most of the cases, with no significant differences between the DVHs obtained from both calculations. However, deviations of up to 4% for the dose received by 95% of the target volume were found for the small lung tumors. Therefore, the approximations in the C/S algorithm slightly influence the accuracy in small lung tumors even though the C/S algorithm of the tomotherapy system shows very good overall behavior.
Analysis of outcomes in radiation oncology: An integrated computational platform
Authors: Liu Dezhi , Ajlouni Munther , Jin Jian‐Yue , Ryu Samuel , Siddiqui Farzan , Patel Anushka , Movsas Benjamin , Chetty Indrin J.
Published: April 2009

Radiotherapy research and outcome analyses are essential for evaluating new methods of radiation delivery and for assessing the benefits of a given technology on locoregional control and overall survival. In this article, a computational platform is presented to facilitate radiotherapy research and outcome studies in radiation oncology. This computational platform consists of (1) an infrastructural database that stores patient diagnosis, IMRT treatment details, and follow‐up information, (2) an interface tool that is used to import and export IMRT plans in DICOM RT and AAPM/RTOG formats from a wide range of planning systems to facilitate reproducible research, (3) a graphical data analysis and programming tool that visualizes all aspects of an IMRT plan including dose, contour, and image data to aid the analysis of treatment plans, and (4) a software package that calculates radiobiological models to evaluate IMRT treatment plans. Given the limited number of general‐purpose computational environments for radiotherapy research and outcome studies, this computational platform represents a powerful and convenient tool that is well suited for analyzing dose distributions biologically and correlating them with the delivered radiation dose distributions and other patient‐related clinical factors. In addition the database is web‐based and accessible by multiple users, facilitating its convenient application and use.
Automatic image‐to‐world registration based on x‐ray projections in cone‐beam CT‐guided interventions
Authors: Hamming N. M. , Daly M. J. , Irish J. C. , Siewerdsen J. H.
Published: April 2009

Intraoperative imaging offers a means to account for morphological changes occurring during the procedure and resolve geometric uncertainties via integration with a surgical navigation system. Such integration requires registration of the image and world reference frames, conventionally a time consuming, error‐prone manual process. This work presents a method of automatic image‐to‐world registration of intraoperative cone‐beam computed tomography (CBCT) and an optical tracking system. Multimodality (MM) markers consisting of an infrared (IR) reflective sphere with a tungsten sphere (BB) placed precisely at the center were designed to permit automatic detection in both the image and tracking (world) reference frames. Image localization is performed by intensity thresholding and pattern matching directly in 2D projections acquired in each CBCT scan, with 3D image coordinates computed using backprojection and accounting for C‐arm geometric calibration. The IR tracking system localized MM markers in the world reference frame, and the image‐to‐world registration was computed by rigid point matching of image and tracker point sets. The accuracy and reproducibility of the automatic registration technique were compared to conventional (manual) registration using a variety of marker configurations suitable to neurosurgery (markers fixed to cranium) and head and neck surgery (markers suspended on a subcranial frame). The automatic technique exhibited subvoxel marker localization accuracy for all marker configurations. The fiducial registration error of the automatic technique was , compared to for the manual technique, indicating improved accuracy and reproducibility. The target registration error (TRE) averaged over all configurations was for the automatic technique, compared to for the manual in accuracy, although the difference was not statistically significant . A statistically significant improvement in precision was observed—specifically, the standard deviation in TRE was for the automatic technique versus for the manual technique . The projection‐based automatic registration technique demonstrates accuracy and reproducibility equivalent or superior to the conventional manual technique for both neurosurgical and head and neck marker configurations. Use of this method with C‐arm CBCT eliminates the burden of manual registration on surgical workflow by providing automatic registration of surgical tracking in 3D images within of acquisition, with registration automatically updated with each CBCT scan. The automatic registration method is undergoing integration in ongoing clinical trials of intraoperative CBCT‐guided head and neck surgery.
Clinical MR Imaging and Physics: A Tutorial
Authors: Thompson R. Terry
Published: April 2009

Clinical MR Imaging and Physics: A Tutorial Chrysikopoulos Haris S. Springer Science + Business Medica, LLC, New York, NY 2009. Softcover 176 pp. Price: $109.00. ISBN: 9783540779995.
Pharmacological Exploitation of an Off-Target Antibacterial Effect of the Cyclooxygenase-2 Inhibitor Celecoxib against
Francisella tularensis
Authors: Chiu Hao-Chieh , Yang Jian , Soni Shilpa , Kulp Samuel K. , Gunn John S. , Schlesinger Larry S. , Chen Ching-Shih
Published: April 2009

Francisella tularensis
, a bacterium which causes tularemia in humans, is classified as a CDC category A bioterrorism agent. In this study, we demonstrate that celecoxib, an anti-inflammatory cyclooxygenase-2 inhibitor in clinical use, exhibits activity against a type A strain of
F. tularensis
(Schu S4), the live vaccine strain of
F. tularensis
(a type B strain), and
F. novicida
(“
F. tularensis
subsp.
novicida
”) directly in growth medium. This bacterial killing, however, was not noted with rofecoxib, despite its higher potency than that of celecoxib in inhibiting cyclooxygenase-2. The unique ability of celecoxib to inhibit the proliferation of
F. tularensis
could be pharmacologically exploited to develop novel anti-
Francisella
therapeutic agents, of which the proof of principle is demonstrated by compound 20, a celecoxib derivative identified through the screening of a celecoxib-based focused compound library. Compound 20 inhibited the intracellular proliferation of
Francisella
in macrophages without causing appreciable toxicity to these host cells. Together, these data support the translational potential of compound 20 for the further development of novel, potent anti-
Francisella
agents.
Alkoxyalkyl Esters of 9-(
S
)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent and Selective Inhibitors of Hepatitis B Virus (HBV) Replication In Vitro and in HBV Transgenic Mice In Vivo
Authors: Morrey John D. , Korba Brent E. , Beadle James R. , Wyles David L. , Hostetler Karl Y.
Published: April 2009

Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(
S
)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(
S
)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (
S
)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (
S
)-HPMPA were 6 to 20 times more active than unmodified (
S
)-HPMPA on the basis of their 50% effective concentrations in 2.2.15 cells. The increased antiviral activity appeared to be due in part to the increased uptake and conversion of HDP-(
S
)-HPMPA to HPMPA diphosphate observed in HepG2 cells in vitro. HDP-(
S
)-HPMPA retained full activity against HBV mutants resistant to lamivudine (L180M, M204V), but cross-resistance to a mutant resistant to adefovir (N236T) was detected. HDP-(
S
)-HPMPA is orally bioavailable and provides excellent liver exposure to the drug. Oral treatment of HBV transgenic mice with HDP-(
S
)-HPMPA, 15M-HDP-(
S
)-HPMPA, and ODE-(S)-HPMPA for 14 days reduced liver HBV DNA levels by roughly 1.5 log units, a response equivalent to that of adefovir dipivoxil.
Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration
Authors: Li Meng , Andrew Marilee A. , Wang Joanne , Salinger David H. , Vicini Paolo , Grady Richard W. , Phillips Brian , Shen Danny D. , Anderson Gail D.
Published: April 2009

Cranberry juice consumption is often recommended along with low-dose oral antibiotics for prophylaxis for recurrent urinary tract infection (UTI). Because multiple membrane transporters are involved in the intestinal absorption and renal excretion of β-lactam antibiotics, we evaluated the potential risk of pharmacokinetic interactions between cranberry juice and the β-lactams amoxicillin (amoxicilline) and cefaclor. The amoxicillin-cranberry juice interaction was investigated in 18 healthy women who received on four separate occasions a single oral test dose of amoxicillin at 500 mg and 2 g with or without cranberry juice cocktail (8 oz) according to a crossover design. A parallel cefaclor-cranberry juice interaction study was also conducted in which 500 mg cefaclor was administered with or without cranberry juice cocktail (12 oz). Data were analyzed by noncompartmental methods and nonlinear mixed-effects compartmental modeling. We conclude that the concurrent use of cranberry juice has no significant effect on the extent of oral absorption or the renal clearance of amoxicillin and cefaclor. However, delays in the absorption of amoxicillin and cefaclor were observed. These results suggest that the use of cranberry juice at usual quantities as prophylaxis for UTI is not likely to alter the pharmacokinetics of these two oral antibiotics.
Chlamydial Heat Shock Protein 60 Induces Acute Pulmonary Inflammation in Mice via the Toll-Like Receptor 4- and MyD88-Dependent Pathway
Authors: Bulut Yonca , Shimada Kenichi , Wong Michelle H. , Chen Shuang , Gray Pearl , Alsabeh Randa , Doherty Terence M. , Crother Timothy R. , Arditi Moshe
Published: April 2009

Heat shock protein 60 derived fromChlamydia pneumoniae(cHSP60) activates Toll-like receptor 4 (TLR4) signaling through the MyD88 pathway in vitro, but it is not known how cHSP60 contributes toC. pneumoniae-induced lung inflammation. We treated wild-type (WT), TLR2−/−, TLR4−/−, or MyD88−/−mice intratracheally (i.t.) with recombinant cHSP60 (50 μg), UV-killedC. pneumoniae(UVCP; 5 × 106inclusion-forming units/mouse), lipopolysaccharide (2 μg), or phosphate-buffered saline (PBS) and sacrificed mice 24 h later. Bronchoalveolar lavage (BAL) was obtained to measure cell counts and cytokine levels, lungs were analyzed for histopathology, and lung homogenate chemokine concentrations were determined. Bone marrow-derived dendritic cells (BMDDCs) were generated and stimulated with liveC. pneumoniae(multiplicity of infection [MOI], 5), UVCP (MOI, 5), or cHSP60 for 24 h, and the expression of costimulatory molecules (CD80 and CD86) was measured by fluorescence-activated cell sorting. cHSP60 induced acute lung inflammation with the same intensity as that of UVCP-induced inflammation in WT mice but not in TLR4−/−or MyD88−/−mice. cHSP60- and UVCP-induced lung inflammation was associated with increased numbers of cells in BAL, increased neutrophil recruitment, and elevated BAL interleukin-6 (IL-6) levels. Both cHSP60 and UVCP induced IL-6 release and CD80 and CD86 expression in WT cells but not in MyD88−/−BMDDCs. cHSP60 stimulated DC activation in a TLR4- and MyD88-dependent manner with an intensity similar to that induced by UVCP. These data suggest that cHSP60 promotes lung inflammation and DC activation via TLR4 and MyD88 and therefore may play a significant role in the pathogenesis ofC. pneumoniae-induced chronic inflammatory lung diseases.
Bivalent Recombinant Vaccine for Botulinum Neurotoxin Types A and B Based on a Polypeptide Comprising Their Effector and Translocation Domains That Is Protective against the Predominant A and B Subtypes
Authors: Shone Clifford , Agostini Heidi , Clancy Joanna , Gu Mili , Yang Huei-Hsiung , Chu Yanfang , Johnson Virginia , Taal Makie , McGlashan Joanna , Brehm John , Tong Xiaomi
Published: April 2009

The botulinum neurotoxins (BoNTs) are a large family of extremely potent, neuroparalytic, dichain proteins which act at the peripheral nervous system. The wide genetic diversity observed with this neurotoxin family poses a significant challenge for the development of an effective botulinum vaccine. The present study describes a vaccine development platform based on protein fragments representing the N-terminal two-thirds of each toxin molecule. These fragments, designated LHN, comprise the light chain and translocation domains of each neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized genes, LHNfragments derived from BoNT serotypes A and B were expressed inEscherichia coliin high yield with >1 g of purified, soluble fragment recoverable from 4.5 liter-scale fermentations. The protective efficacy of LHN/A was significantly enhanced by treatment with formaldehyde, which induced intramolecular cross-linking but virtually no aggregation of the fragment. A single immunization of the modified fragment protected mice from challenge with a 10350% lethal dose (LD50) of BoNT/A1with an 50% effective dose (ED50) of 50 ng of the vaccine. In similar experiments, the LHN/A vaccine was shown to protect mice against challenge with BoNT/A subtypes A1, A2, and A3, which is the first demonstration of single-dose protection by a vaccine against the principal toxin subtypes of BoNT/A. The LHN/B vaccine was also highly efficacious, giving an ED50of ∼140 ng to a challenge of 103LD50of BoNT/B1. In addition, LHN/B provided single-dose protection in mice against BoNT/B4(nonproteolytic toxin subtype).
Mycobacterium aviumsubsp.paratuberculosisFibronectin Attachment Protein Activates Dendritic Cells and Induces a Th1 Polarization
Authors: Lee Jun Sik , Shin Sung Jae , Collins Michael T. , Jung In Duk , Jeong Young-Il , Lee Chang-Min , Shin Yong Kyoo , Kim Daejin , Park Yeong-Min
Published: April 2009

Paratuberculosis is a chronic infectious disorder and a major problem in farmed ruminants. This disease is caused byMycobacterium aviumsubsp.paratuberculosis.M. aviumsubsp.paratuberculosisis an important pathogen that causes Johne's disease in animals and also has been implicated as a possible cause of Crohn's disease in humans, but little is known about the protective immune responses to this microorganism. Fibronectin attachment protein (FAP) is a member of a family of fibronectin-binding proteins produced by several species of mycobacteria which is important in the pathogenesis ofM. avium. Addition of recombinant FAP to human respiratory tract organ cultures inhibitsM. aviumbinding to areas where there is epithelial damage. We characterized the role of FAP in promoting adaptive and innate immune responses. FAP functionally activated dendritic cells by augmenting the expression of CD80, CD86, major histocompatibility complex class I, and major histocompatibility complex class II. Moreover, FAP induced the allogeneic immunostimulatory capacity of dendritic cells by stimulating dendritic cell production of Th1-promoting interleukin-12. FAP also increased the production of gamma interferon by T cells in mixed-lymphocyte reactions, which would be expected to contribute to the Th1 polarization of the immune response. The expression of surface markers and cytokine production in dendritic cells was mediated by both mitogen-activated protein kinases and NF-κB pathways. These results show that FAP modulates the adaptive immune responses toM. aviumsubsp.paratuberculosisby inducing maturation and activation of dendritic cells, which drives Th1 polarization.
Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia: Figure 1
Authors: Khan S , Del-Duca C , Fenton E , Holding S , Hirst J , Doré P C , Sewell W A C
Published: April 2009

Background:

The appropriate testing strategy for diagnosing pernicious anaemia using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is controversial. Intrinsic factor antibodies are found in only about 70% of cases. Indirect immunofluorescence screening for gastric parietal cell antibodies is more sensitive, labour intensive, and less specific.

Methods:

The frequency of antibody positivity (IFA and/or GPC) was retrospectively examined in patients tested for both autoantibodies over a three-year period. It was investigated whether B12 levels were related to antibody status. These findings were validated in a prospective study of IFA in 91 GPC negative patients with low B12 levels.

Results:

Of 847 samples identified in the retrospective study, 4 (0.47%) were positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC alone, and 112 (13.2%) for both. Student t test on log-transformed data showed B12 levels had no bearing on autoantibody status. 91 consecutive patients with low B12 levels were tested for both autoantibodies; all were negative for gastric parietal cell antibodies. Only one sample was positive for intrinsic factor antibody using the porcine intrinsic factor assay, but was negative by a human recombinant intrinsic factor-based ELISA.

Conclusions:

This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.
MicroRNA involvement in the pathogenesis and management of breast cancer
Authors: Khoshnaw S M , Green A R , Powe D G , Ellis I O
Published: April 2009

MicroRNAs (miRNAs) are a highly abundant class of endogenous small non-coding RNAs (18–25 nucleotides in length) that regulate gene expression by targeting protein-coding mRNAs post-transcriptionally. miRNAs have been implicated in cancer development and progression. As miRNAs and their regulatory functions are further revealed, the more the importance of miRNA-directed gene regulation is emphasised. In the human genome, 695 mature miRNAs have been identified, although computational calculation predicts that this may increase to >1000. Deregulation of miRNA expression profiles is thought to be implicated in the pathogenesis of many human cancers including breast tumours. Breast cancer subtypes are observed to have deranged miRNA expression signatures, which makes miRNAs important targets for developing a novel molecular classification of breast cancer and opening avenues for more individualised treatment strategies for patients with breast cancer.
Planktivore vertical migration and shoaling under a subarctic light regime
Authors: Gjelland Karl Øystein , Bøhn Thomas , Horne John K. , Jensvoll Ingrid , Knudsen Frank Reier , Amundsen Per-Arne
Published: April 2009

Visually foraging planktivorous fish are prey of visual predators, and their foraging behaviour may be affected by light levels both in terms of gain and risk. The large seasonal change in day length throughout a subarctic summer at 69°N was used to show the influence of light on diel vertical migration (DVM) and shoaling patterns in a planktivorous fish assemblage consisting of two species ( Coregonus lavaretus and Coregonus albula ). Under the midnight sun in June, night and daytime behaviour was similar, with extensive shoaling and limited DVM. With increasingly darker nights towards autumn, the fish dispersed during the dark hours and showed more extensive DVM. Throughout the changing light regime of both the day and the season, the planktivores consistently chose depths with light levels compatible with visual foraging and reduced predation risk as revealed from reactive distance modelling of coregonids and their salmonid predators. The findings support the hypothesis that behavioural decisions are based on a trade-off between foraging rate and predation risk, and increased predator avoidance behaviour towards autumn suggests that this trade-off is state-dependent.
Influences on the natural reproduction of whitefish (Coregonus lavaretus) in Lake Constance
Authors: Wahl Bernd , Löffler Herbert
Published: April 2009

The conditions for the natural reproduction of whitefish ( Coregonus lavaretus ) in Lake Constance have been subject to strong variations during recent decades by the impact of fishing and trophic changes. We analysed fluctuations of stock size, age structure, spawning time, and amount of sampled eggs of this species. The onset of spawning altered because of changes in the age structure of the stock. We found a clear relation of spawning time to the mean age of the annual catch and the November epilimnion temperature. The quantity of eggs sampled from the lake bottom with a dredge is in relation to the number of female spawners and may serve as an early indicator for stock size changes. The proportion of viable eggs on the lake floor correlates with oxygen concentrations in deep water. Extremely low oxygen conditions and an almost total loss of eggs occurred when the nutrient levels were high and oxygen regeneration by vertical winter mixing was weak. A mathematical model serves to interpret the changing abundance of living eggs on the lake bottom over the course of a season and is also used to estimate mortality rates.
Using nitrogen stable isotopes to detect long-distance movement in a threatened cutthroat trout (Oncorhynchus clarkii utah)
Authors: Sepulveda Adam J. , Colyer Warren T. , Lowe Winsor H. , Vinson Mark R.
Published: April 2009

Interior cutthroat trout occupy small fractions of their historic ranges and existing populations often are relegated to headwater habitats. Conservation requires balancing protection for isolated genetically pure populations with restoration of migratory life histories by reconnecting corridors between headwater and mainstem habitats. Identification of alternative life history strategies within a population is critical to these efforts. We tested the application of nitrogen stable isotopes to discern fluvial from resident Bonneville cutthroat trout (BCT; Oncorhynchus clarkii utah ) in a headwater stream. Fluvial BCT migrate from headwater streams with good water quality to mainstem habitats with impaired water quality. Resident BCT remain in headwater streams. We tested two predictions: (i) fluvial BCT have a higher δ15N than residents, and (ii) fluvial BCT δ15N reflects diet and δ15N enrichment characteristics of mainstem habitats. We found that fluvial δ15N was greater than resident δ15N and that δ15N was a better predictor of life history than fish size. Our data also showed that fluvial and resident BCT had high diet overlap in headwater sites and that δ15N of lower trophic levels was greater in mainstem sites than in headwater sites. We conclude that the high δ15N values of fluvial BCT were acquired in mainstem sites.
Recruitment of North Sea cod (Gadus morhua) and Norway pout (Trisopterus esmarkii) between 1992 and 2006: the interplay between climate influence and predation
Authors: Kempf Alexander , Floeter Jens , Temming Axel
Published: April 2009

The interplay between temperature-related processes and predation in determining age-1 recruitment strength between 1992 and 2006 was analysed for North Sea cod ( Gadus morhua ) and Norway pout ( Trisopterus esmarkii ). For this purpose, an predation impact index (PI) was calculated out of survey data. PI was assumed to depend on the abundance of the predators and on the spatial overlap between predator and prey populations. Generalized additive models (GAMs) were created with spawning stock biomass (SSB) and sea surface temperature (SST) in the respective spawning and nursery areas and PI as explaining variables. SSB had no significant impact on recruitment during this time period for both species. SSTs during spring and PI explained the interannual variability in recruitment strength to a large extent (88% of the total variance for cod and 68% for Norway pout). The SST during spring determined the overall level of recruitment. At SSTs above a certain level, however, the effect on recruitment was no longer significant. In these temperature ranges, predation was the dominant effect. Therefore, the fate of North Sea cod and Norway pout stocks under global-warming conditions will be strongly influenced by the status of the North Sea food web.
Simulation d’un modèle de la source vocale et détermination des paramètres de commande
Authors: Falek L. , Teffahi H. , Djeradi A.
Published: April 2009

Nous présentons une étude paramétrique d’un modèle de la source vocale, connu comme modèle à deux masses. Ce modèle nous a permis de caractériser la fréquence fondamentale de la source en fonction de la pression des poumons et la tension des cordes vocales. Les résultats d’une telle étude contribuent à une meilleure connaissance de la réponse d’un modèle des cordes vocales désormais classique.
EPIDEMICS OF SIRS MODEL WITH NONUNIFORM TRANSMISSION ON SCALE-FREE NETWORKS
Authors: XIA C. Y. , SUN S. W. , LIU Z. X. , CHEN Z. Q. , YUAN Z. Z.
Published: April 2009

We investigate the effect of nonuniform transmission on the critical threshold of susceptible–infected–recovered–susceptible (SIRS) epidemic model on scale-free networks. Based on the mean-field theory, it is observed that the epidemic threshold is not only correlated with the topology of underlying networks, but also with the disease transmission mechanism (e.g., nonuniform transmission). The current findings will significantly help us to further understand the real epidemics taking place on social and technological networks.
FUNCTIONAL SYNCHRONIZATION AND ITS APPLICATION TO SECURE COMMUNICATIONS
Authors: BANERJEE SANTO , CHOWDHURY A. ROY
Published: April 2009

A new kind of synchronization in which some well-defined functions of dynamical variables tend to each other as time evolves is shown to take place in two distinct three-dimensional nonlinear systems. This new kind of functional synchronization is analyzed using the partial Lyapunov functions which help one to construct the functions of the nonlinear variables which synchronize. In the next phase we show how one can develop a set of keys to encode and decode a signal which is to be transmitted. Since the key construction is very much dependent on the chosen function, the whole system is highly secure.
COUPLING-INDUCED SPIKING COHERENCE IN COUPLED SUBTHRESHOLD NEURONS
Authors: LIM WOOCHANG , KIM SANG-YOON
Published: April 2009

We consider a large ensemble of globally coupled subthreshold Morris–Lecar neurons. We numerically investigate collective coherence of noise-induced spikings by varying the coupling strength J. As J passes a lower threshold, a transition to collective spiking coherence, which is described in terms of an order parameter, occurs because the coupling stimulates coherence between noise-induced spikings. However, when passing a higher threshold, the coupling induces oscillator death (i.e., quenching of noise-induced spikings) because each neuron is attracted to a noisy equilibrium state. Through competition of these two different roles of coupling, coupling-induced spiking coherence is found to occur in a large range of intermediate coupling strength. The degree of spiking coherence is well-characterized in terms of a coherence measure reflecting the degree of "resemblance" of the global potential to the local potential.