bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of temperature on the growth of ultrathin films of p-sexiphenyl on KCl(001)
Authors: Kintzel E. J. , Smilgies D.-M. , Skofronick J. G. , Safron S. A. , Van Winkle D. H.
Published: March 2004

Ultrathin films of p-sexiphenyl, formed by vapor-deposition onto KCl(001) substrates, have been investigated by x-ray diffraction (XRD) and atomic force microscopy (AFM). Analysis of the XRD data shows that the temperature of the alkali halide substrate during deposition affects the orientations of the molecules within the adsorbed films. AFM images contribute independent evidence consistent with the XRD results. The results are reproducible and suggest that ultrathin films of p-6P molecules can be grown with desired molecular orientations by carefully selecting the appropriate substrate temperature during deposition.
Surface chemical changes of aluminum during NF3-based plasma processing used for in situ chamber cleaning
Authors: Li Xi , Hua Xuefeng , Ling Li , Oehrlein Gottlieb S. , Karwacki E. , Ji Bing
Published: March 2004

During plasma-based in situ chamber cleaning of deposited dielectric films using NF3, a transformation of aluminum chamber parts into AlFx can take place. We studied the roles of fluorine atoms and ion bombardment in this process by employing NF3 discharges mixed with He, Ne, or Ar interacting with or without ion bombardment with sputter-deposited Al films on silicon. Aluminum oxide erosion rates and surface chemistry changes, and information on the species that evolve from the surfaces during the process, were obtained by real-time ellipsometry and mass spectrometry, respectively. Characterization of processed Al surfaces was also performed using x-ray photoelectron spectroscopy. We find that Al oxide is rapidly removed/transformed in NF3 discharges and also for C2F6/O2 rf powered discharges. We observe a complex interactive role of fluorine atoms and ion bombardment that leads to the formation of thick fluorinated Al reaction layers during exposure of Al to NF3-containing rf plasmas. For NF3-rich rf discharges, the Al fluoride layer thickness continues to grow as a function of time, without saturation. The Al fluoride layer formation can be prevented if NF3/noble gas mixtures containing a high noble gas proportion are employed instead. An increasingly thicker Al fluoride layer is produced with a greater proportion of NF3 in He/NF3, Ne/NF3, and Ar/NF3.
Characteristics and anticoagulation behavior of polyethylene terephthalate modified by C2H2 plasma immersion ion implantation-deposition
Authors: Wang J. , Pan C. J. , Kwok S. C. H. , Yang P. , Chen J. Y. , Wan G. J. , Huang N. , Chu P. K.
Published: March 2004

Acetylene (C2H2) plasma immersion ion implantation-deposition (PIII-D) is conducted on polyethylene terephthalate (PET) to improve its blood compatibility. The structural and physicochemical properties of the modified surface are characterized by, Raman spectroscopy, x-ray photoelectron spectroscopy (XPS), and static contact angle measurement. Atomic force microscopy discloses that the average roughness (Ra) of film surface decreases from 58.9 nm to 11.4 nm after C2H2 PIII-D treats PET. Attenuated total reflection Fourier transform infrared spectroscopy shows that the specfic adsorption peaks for PET decrease after ion implantation and deposition. Raman spectroscopy indicates that a thin amorphous polymerlike carbon (PLC) film is formed in the PET. The effects of the surface modification on the chemical bonding of C, H, and O are examined by XPS and the results show that the ratio of sp3 C–C to sp2 C=C is 0.25. After C2H2 PIII-D, the polar component γp of surface energy increases from 2.4 mN/m to 12.3 mN/m and γp/γd increases from 0.06 to 0.35. The wettability of the modified surfaces is improved. Scanning electron microscopy and optical microscopy reveal that the amounts of adhered, aggregated and morphologically changed platelets are reduced by the deposition of an amorphous polymer-like carbon film. The thrombin time, prothrombin time, and activated partial thromboplastin time of the modified PET are longer than those of the untreated PET. Our result thus shows that the amorphous PLC film deposited on the PET surface by C2H2 PIII-D improves platelet adhesion and activation.
Chemical states and band offsets of NH3-treated Si oxynitride films studied by high-resolution photoelectron spectroscopy
Authors: Oshima M. , Toyoda S. , Okabayashi J. , Kumigashira H. , Ono K. , Niwa M. , Usuda K. , Hirashita N.
Published: March 2004

Ultrathin SiON films formed by thermal nitridation of SiO2 films with NH3 gas are analyzed by high-resolution angle-resolved photoelectron spectroscopy to investigate the interfacial chemistry, the chemical state in-depth distribution of nitrogen atoms, and the band offsets. Although nitrogen atoms are mostly homogeneously distributed in the NH3-treated SiON films, the [Si–Si3−xOx]3N or [Si–N3−xOx]3N component exists closer to the surface than the [Si–Si3−xNx]3N or Si3N4 component. The valence-band offsets of HN3-treated SiON films are determined by a substrate subtraction method to be 4.4 eV. This is the same as for SiO2 film. Valence-band offsets for NO-treated SiON film are measured to be 4.4 eV for SiO2/Si and 3.3 eV for SiON/Si. Furthermore, O 1s loss spectra reveal that SiON films consist mainly of a SiO2 region with a band gap of 8.9 eV, and a smaller region of probably Si3N4 with a band gap of about 5.3 eV.
Evolution of surface roughness during metal silicides phase transformation
Authors: Pang C. H. , Hing P. , Zhao F. F. , See A. , Chong Y. F. , Lee P. S.
Published: March 2004

This study monitors systematically the evolution of surface roughness during metal (Ti, Co, and Ni) silicides phase transformation and coupling to other physical parameters. During metal/silicon reaction film surface roughness evolves due to the effect of nucleation and growth of metal silicides and is sensitive to different processing conditions. In general, surface roughness increases as new phases are formed and decreases during grain growth. The difference in roughness between processes indicates whether a process is more inferior for new phase formation. The correlation of surface roughness towards sheet resistance, film thickness, and phase transformation are found to be independent of film thickness in C49-to-C54 TiSi2 polymorphic transformation but not for Co and Ni silicides. Any abnormalities from the trend indicate that the film is experiencing a physical degradation.
Power transmission in L-shaped plates including flexural and in-plane vibration
Authors: Kessissoglou Nicole J.
Published: March 2004

In this paper, power flow propagation in plates connected in an L-joint is investigated in both the low and high frequency ranges. An exact solution is derived to describe the flexural, in-plane longitudinal and in-plane shear wave motion in the plates. The coupled plates are simply supported along two parallel sides, and free at the other two ends. A point force is used to generate flexural wave motion only. The flexural wave coefficients are determined from the boundary conditions, continuity equations at the driving force locations, and continuity equations at the corner junction of the plates. Structural intensity expressions are used to examine the structural noise transmission in the low and high frequency ranges. The contributions from the individual wave types are also examined.
Spectral-temporal factors in the identification of environmental sounds
Authors: Gygi Brian , Kidd Gary R. , Watson Charles S.
Published: March 2004

Three experiments tested listeners’ ability to identify 70 diverse environmental sounds using limited spectral information. Experiment 1 employed low- and high-pass filtered sounds with filter cutoffs ranging from 300 to 8000 Hz. Listeners were quite good (>50% correct) at identifying the sounds even when severely filtered; for the high-pass filters, performance was never below 70%. Experiment 2 used octave-wide bandpass filtered sounds with center frequencies from 212 to 6788 Hz and found that performance with the higher bandpass filters was from 70%–80% correct, whereas with the lower filters listeners achieved 30%–50% correct. To examine the contribution of temporal factors, in experiment 3 vocoder methods were used to create event-modulated noises (EMN) which had extremely limited spectral information. About half of the 70 EMN were identifiable on the basis of the temporal patterning. Multiple regression analysis suggested that some acoustic features listeners may use to identify EMN include envelope shape, periodicity, and the consistency of temporal changes across frequency channels. Identification performance with high- and low-pass filtered environmental sounds varied in a manner similar to that of speech sounds, except that there seemed to be somewhat more information in the higher frequencies for the environmental sounds used in this experiment.
Boundary element modeling of the external human auditory system
Authors: Walsh Timothy , Demkowicz Leszek , Charles Richard
Published: March 2004

In this paper the response of the external auditory system to acoustical waves of varying frequencies and angles of incidence is computed using a boundary element method. The resonance patterns of both the ear canal and the concha are computed and compared with experimental data. Specialized numerical algorithms are developed that allow for the efficient computation of the eardrum pressures. In contrast to previous results in the literature that consider only the “blocked meatus” configuration, in this work the simulations are conducted on a boundary element mesh that includes both the external head/ear geometry, as well as the ear canal and eardrum. The simulation technology developed in this work is intended to demonstrate the utility of numerical analysis in studying physical phenomena related to the external auditory system. Later work could extend this towards simulating in situ hearing aids, and possibly using the simulations as a tool for optimizing hearing aid technologies for particular individuals.
Criteria for discretization of seafloor bathymetry when using a stairstep approximation: Application to computation of T-phase seismograms
Authors: de Groot-Hedlin Catherine
Published: March 2004

Acoustic solutions for numerical models in which an overly coarse discretization of a stairstep boundary is employed to simulate smoothly varying bathymetry are degraded in a way that simulates scattering. Geometrical optics approximations are used to derive discretization criteria for simulating a smoothly sloping interface for the case of a source embedded in either an acoustic or an elastic seafloor, and applied to modeling T-phases. A finite difference time-domain modeling approach is used to synthesize T-phases for both smoothly sloping and rough seafloor boundaries. It is shown that scattering at a rough seafloor boundary yields ocean-borne acoustic phases with velocities near those of observed T-phase, while smooth seafloor models yield T-phases with slower horizontal velocities. The long duration of the computed T-phases for both the rough acoustic and elastic models is consistent with energy being scattered into the sound channel both as it transits the ocean/crust boundary, as well as at several subsequent seafloor reflections. However, comparison between the elastic and acoustic modeling solutions indicates that the T-phase wavetrain duration decreases with decreasing impedence contrast between the ocean and seafloor.
Call recognition in the bullfrog, Rana catesbeiana: Generalization along the duration continuum
Authors: Simmons Andrea Megela
Published: March 2004

Male bullfrogs emit multicroak, quasiharmonic advertisement calls that function in mate attraction and neighbor recognition. The degree of variability of acoustic features in these calls can influence perceptual decisions by conspecific receivers. Analysis of duration of individual croaks in spontaneous advertisement calls of a sample of males shows considerable intraindividual variability in this feature, even within short chorusing bouts. The influence of this intraindividual variability on behavior was examined in a series of evoked calling experiments. When presented with synthetic calls whose croak durations varied over the range of the natural variability in this feature, males responded similarly to intermediate and long duration croaks, but significantly less to short duration croaks. When presented with playbacks of calls with croak durations outside the natural range of variability, males again responded significantly less to shorter durations. The response gradient for duration is thus asymmetrical, with stimuli at the shorter end of the continuum evoking fewer responses than stimuli at the longer end. This asymmetry may be related to the biological demands of rejecting perception of heterospecific advertisement calls, and of mediating appropriate responses to conspecific aggressive calls. The shape of the response gradient for duration may reflect a process of stimulus generalization.
Optoacoustic generation of a helicoidal ultrasonic beam
Authors: Gspan Stefan , Meyer Alex , Bernet Stefan , Ritsch-Marte Monika
Published: March 2004

The optoacoustic generation of a helicoidal ultrasonic beam is demonstrated. Such an ultrasonic “doughnut” beam has a pressure amplitude minimum in the center along its entire longitudinal extension, and it carries orbital angular momentum. It is produced by illuminating a specially structured absorbing surface in a water tank with pulsed laser light. The absorbing surface has a profile with a screw dislocation, similar to the transverse cross-sectional surface of a helix. Upon illumination with modulated light, a correspondingly prepared absorber generates an ultrasonic wave with the desired phase discontinuity in its wave front, which propagates through the water tank and is detected with spatial resolution using a scanning needle hydrophone. This situation can be viewed as the optoacoustic realization of a diffractive acoustical element. The method can be extended to tailor optoacoustically generated ultrasonic waves in a customized way.
Acoustic diagnosis for porous medium with circular cylindrical pores
Authors: Roh Heui-Seol , Yoon Suk Wang
Published: March 2004

Acoustic transmission coefficient and phase velocity of a Lucite slab with circular cylindrical pores with a nonrigid pore frame were experimentally and theoretically investigated. For theoretical investigation a new phenomenological model, the modified Biot-Attenborough (MBA) model, was proposed. The MBA model takes into account both the first kind and the second kind of waves introduced by Biot. It also separately considers viscous and thermal effects with three new phenomenological parameters: boundary, phase velocity, and impedance parameters. The theoretical estimation with three phenomenological parameters shows reasonably good agreement with the experimental data. The physical characteristics of porous medium such as porosity and pore size can be inversely analyzed in terms of the acoustic data such as the transmission coefficient and phase velocity as the functions of porosity and frequency. This makes acoustic diagnosis possible for noninvasively investigating physical characteristics of porous media such as bones and ocean sediments.
On the use of the derivative of electroglottographic signals for characterization of nonpathological phonation
Authors: Henrich Nathalie , d’Alessandro Christophe , Doval Boris , Castellengo Michèle
Published: March 2004

Electroglottography is a common method for providing noninvasive measurements of glottal activity. The derivative of the electroglottographic signal, however, has not attracted much attention, although it yields reliable indicators of glottal closing instants. The purpose of this paper is to provide a guide to the usefulness of this signal. The main features that are to be found in this signal are presented on the basis of an extensive analysis of a database of items sung by 18 trained singers. Glottal opening and closing instants are related to peaks in the signal; the latter can be used to measure glottal parameters such as fundamental frequency and open quotient. In some cases, peaks are doubled or imprecise, which points to special (but by no means uncommon) glottal configurations. A correlation-based algorithm for the automatic measurement of fundamental frequency and open quotient using the derivative of electroglottographic signals is proposed. It is compared to three other electroglottographic-based methods with regard to the measurement of open quotient in inverse-filtered derived glottal flow. It is shown that agreement with the glottal-flow measurements is much better than most threshold-based measurements in the case of sustained sounds.
Spectrum effects of subglottal pressure variation in professional baritone singers
Authors: Sjölander Peta , Sundberg Johan
Published: March 2004

The audio signal from five professional baritones was analyzed by means of spectrum analysis. Each subject sang syllables [pæ] and [pa] from loudest to softest phonation at fundamental frequencies representing 25%, 50%, and 75% of his total range. Ten subglottal pressures, equidistantly spaced between highest and lowest, were selected for analysis along with the corresponding production of the vowels. The levels of the first formant and singer’s formant were measured as a function of subglottal pressure. Averaged across subjects, vowels, and F0, a 10-dB increase at 600 Hz was accompanied by a 16-dB increase at 3 kHz.
The influence of transducer operating point on distortion generation in the cochlea
Authors: Sirjani Davud B. , Salt Alec N. , Gill Ruth M. , Hale Shane A.
Published: March 2004

Distortion generated by the cochlea can provide a valuable indicator of its functional state. In the present study, the dependence of distortion on the operating point of the cochlear transducer and its relevance to endolymph volume disturbances has been investigated. Calculations have suggested that as the operating point moves away from zero, second harmonic distortion would increase. Cochlear microphonic waveforms were analyzed to derive the cochlear transducer operating point and to quantify harmonic distortions. Changes in operating point and distortion were measured during endolymph manipulations that included 200-Hz tone exposures at 115-dB SPL, injections of artificial endolymph into scala media at 80, 200, or 400 nl/min, and treatment with furosemide given intravenously or locally into the cochlea. Results were compared with other functional changes that included action potential thresholds at 2.8 or 8 kHz, summating potential, endocochlear potential, and the 2 f1–f2 and f2–f1 acoustic emissions. The results demonstrated that volume disturbances caused changes in the operating point that resulted in predictable changes in distortion. Understanding the factors influencing operating point is important in the interpretation of distortion measurements and may lead to tests that can detect abnormal endolymph volume states.
Analysis of strong scattering at the micro-scale
Authors: van Wijk Kasper , Komatitsch Dimitri , Scales John A. , Tromp Jeroen
Published: March 2004

Exploiting the fine structure of strongly scattered waves could provide a wealth of new information in seismology, ultrasonics, acoustics, and other fields that study wave propagation in heterogeneous media. Therefore, noncontacting laser-based measurements of ultrasonic surface waves propagating in a strongly disordered medium are performed in which the ratio of the dominant surface wavelength to the size of a scatterer is large, and waves that propagate through many scatterers are recorded. This allows analysis of scattering-induced dispersion and attenuation, as well as the transition from ballistic to diffusive propagation. Despite the relatively small size of the scatterers, multiple scattering strikingly amplifies small perturbations, making changes even in a single scatterer visible in the later-arriving waveforms. To understand the complexity of the measured waveforms, elastic spectral-element numerical simulations are performed. The multiple-scattering sensitivity requires precise gridding of the actual model, but once this has been accomplished, we obtain good agreement between the measured and simulated waveforms. In fact, the simulations are invaluable in analyzing subtle effects in the data such as weak precursory body-wave diffractions. The flexibility of the spectral-element method in handling media with sharp boundaries makes it a powerful tool to study surface-wave propagation in the multiple-scattering regime.
Chaotic vibrations of a vocal fold model with a unilateral polyp
Authors: Zhang Yu , Jiang Jack J.
Published: March 2004

A nonlinear model was proposed to study chaotic vibrations of vocal folds with a unilateral vocal polyp. The model study found that the vocal polyp affected glottal closure and caused aperiodic vocal fold vibrations. Using nonlinear dynamic methods, aperiodic vibrations of the vocal fold model with a polyp were attributed to low-dimensional chaos. Bifurcation diagrams showed that vocal polyp size, stiffness, and damping had important effects on vocal fold vibrations. An increase in polyp size tended to induce subharmonic patterns and chaos. This study provides a theoretical basis to model aperiodic vibrations of vocal folds with a laryngeal mass.
β lactam monotherapy versus β lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials
Authors: Paul Mical , Benuri-Silbiger Ishay , Soares-Weiser Karla , Leibovici Leonard
Published: March 2004

Objective To compare β lactam monotherapy with β lactam-aminoglycoside combination therapy for severe infections.

Data sources Medline, Embase, Lilacs, Cochrane Library, and conference proceedings, to 2003; references of included studies; contact with all authors. No restrictions, such as language, year of publication, or publication status.

Study selection All randomised trials of β lactam monotherapy compared with β lactam-aminoglycoside combination therapy for patients without neutropenia who fulfilled criteria for sepsis.

Data selection Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary outcome assessed was all cause fatality by intention to treat. Relative risks were pooled with the random effect model (relative risk < 1 favours monotherapy).

Results 64 trials with 7586 patients were included. There was no difference in all cause fatality (relative risk 0.90, 95% confidence interval 0.77 to 1.06). 12 studies compared the same β lactam (1.02, 0.76 to 1.38), and 31 studies compared different β lactams (0.85, 0.69 to 1.05). Clinical failure was more common with combination treatment overall (0.87, 0.78 to 0.97) and among studies comparing different β lactams (0.76, 0.68 to 0.86). There was no advantage to combination therapy among patients with Gram negative infections (1835 patients) or Pseudomonas aeruginosa infections (426 patients). There was no difference in the rate of development of resistance. Nephrotoxicity was significantly more common with combination therapy (0.36, 0.28 to 0.47). Heterogeneity was not significant for these comparisons.

Conclusions In the treatment of sepsis the addition of an aminoglycoside to β lactams should be discouraged. Fatality remains unchanged, while the risk for adverse events is increased.
Modulation of V1-receptor-mediated renal vasoconstriction by epoxyeicosatrienoic acids
Authors: Rajapakse Niwanthi W. , Roman Richard J. , Falck John R. , Oliver Jeremy J. , Evans Roger G.
Published: March 2004

This study examined the effects of renal arterial infusion of a selective cytochrome P-450 epoxygenase inhibitor, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH; 2 mg/kg plus 1.5 mg·kg−1·h−1), on renal hemodynamic responses to infusions of [Phe2,Ile3,Orn8]vasopressin and ANG II into the renal artery of anesthetized rabbits. MS-PPOH did not affect basal renal blood flow (RBF) or cortical or medullary blood flow measured by laser-Doppler flowmetry (CLDF/MLDF). In vehicle-treated rabbits, [Phe2,Ile3,Orn8]vasopressin (30 ng·kg−1·min−1) reduced MLDF by 62 ± 7% but CLDF and RBF were unaltered. In MS-PPOH-treated rabbits, RBF and CLDF fell by 51 ± 8 and 59 ± 13%, respectively, when [Phe2,Ile3,Orn8]vasopressin was infused. MS-PPOH had no significant effects on the MLDF response to [Phe2,Ile3,Orn8]vasopressin (43 ± 9% reduction). ANG II (20 ng·kg−1·min−1) reduced RBF by 45 ± 10% and CLDF by 41 ± 14%, but MLDF was not significantly altered. MS-PPOH did not affect blood flow responses to ANG II. Formation of epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DiHETEs) was 49% lower in homogenates prepared from the renal cortex of MS-PPOH-treated rabbits than from vehicle-treated rabbits. MS-PPOH had no effect on the renal formation of 20-hydroxyeicosatetraenoic acid (20-HETE). Incubation of renal cortical homogenates from untreated rabbits with [Phe2,Ile3,Orn8]vasopressin (0.2–20 ng/ml) did not affect formation of EETs, DiHETEs, or 20-HETE. These results do not support a role for de novo EET synthesis in modulating renal hemodynamic responses to ANG II. However, EETs appear to selectively oppose V1-receptor-mediated vasoconstriction in the renal cortex but not in the medullary circulation and contribute to the relative insensitivity of medullary blood flow to V1-receptor activation.
Texture and microstructure analysis with high-energy synchrotron radiation
Authors: Bunge Hans J.
Published: March 2004

Diffraction of high-energy synchrotron radiation with wavelengths in the range of 0.1 Å, provided by the beamline BW5 at HASYLAB in Hamburg, was used to measure textures (orientation distribution) and microstructures (spatial distribution) of the crystallites in various polycrystalline materials. In order to achieve extremely high angular-combined with very high lateral resolution a continuous sweeping technique with an area detector was employed. This technique “images” three different types of two-dimensional sections and projections of the six-dimensional orientation–location space onto the area detector. In many cases the orientations and locations of all individual grains of the sample can thus be seen simultaneously. The high penetration depth of this radiation in the range of several centimeters (comparable with that of neutrons) allows investigating big or capsulated samples. Examples are given of grain-resolved recrystallization textures, a soldering seam, a filled beverage can, and the orientation distribution of kamacite lamellae in an iron meteorite, elucidating the orientation relationship of the γ→α transformation in iron.
Structural characterization of SiGe and SiGe:C heterostructures using a combination of X-ray scattering methods
Authors: Woitok J. F.
Published: March 2004

This study is about the structural properties of SiGe and SiGe:C heteroepitaxial layers on Si (001). The structural characterization is based on the application of complementary information content of X-ray scattering techniques like high-resolution X-ray diffraction (XRD), X-ray reflectivity (XRR), and X-ray diffuse scattering (XDS). One main focus of the analysis is to derive a sample model that sufficiently describes all experimental datasets. In addition, the reliability of parameters extracted by just one single method is discussed. It turned out that XRR is more sensitive to the near surface region, indicating the presence of surface roughness and density gradients that do not significantly affect the XRD pattern.
Strain effects in thin film/Si substrates revealed by X-ray microdiffraction
Authors: Murray C. E. , Noyan I. C. , Lai B. , Cai Z.
Published: March 2004

The local variation in strain and rotation of the Si substrate due to overlying Ni thin film features has been observed using X-ray microdiffraction. Residual tensile stress in 1 μm thick, 190 μm diameter Ni dots of 990 MPa imparted an average compressive stress in the underlying Si substrate. Ni Kα fluorescence scans, acquired simultaneously with Si (333) diffraction data, allow for a precise determination of the Ni feature edge location relative to the observed shift in Si (333) peak position. Rocking curve mesh scans, in which the sample was translated perpendicular and parallel to the diffraction plane, were used to deconvolute the effects of substrate strain due to d-spacing shifts and rotation of the local Si surface. In addition, shear strains at the dot edge imparted a significant shift in the Si (333) diffraction peak, producing a secondary diffraction peak in modified reciprocal space scans.
Method of semidiscretization in time for quasilinearintegrodifferential equations
Authors: Bahuguna D. , Shukla Reeta
Published: March 2004

We consider a class of quasilinear integrodifferential equations
in a reflexive Banach space. We apply the method of
semidiscretization in time to establish the existence, uniqueness,
and continuous dependence on the initial data of strong solutions.
Binding of heparin to plasma proteins and endothelial surfaces is inhibited by covalent linkage to antithrombin
Authors: Paredes Nethnapha , Thong Bruce , Chindemi Paul , Paes Bosco , Berry Leslie , Monagle Paul , Chan Anthony
Published: March 2004

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are used for prophylaxis and treatment of thrombosis. However, UFH has a short plasma half-life and variable anticoagulant response in vivo due to plasma or vessel wall protein binding and LMWH has a decreased ability to inactivate thrombin, the pivotal enzyme in the coagulation cascade. Covalent linkage of antithrombin to heparin gave a complex (ATH) with superior anticoagulant activity compared to UFH and LMWH, and longer intravenous half-life compared to UFH. We found that plasma proteins bound more to UFH than ATH, and least to LMWH. Also, UFH bound significantly more to endothelial cells than ATH, with 100% of UFH and 94% of ATH binding being on the cell surface and the remainder was endocytosed. Competition studies with UFH confirmed that ATH binding was likely through its heparin moiety. These findings suggest that differences in plasma protein and endothelial cell binding may be due to available heparin chain length. Although ATH is polydisperse, the covalently-linked antithrombin may shield a portion of the heparin chain from association with plasma or endothelial cell surface proteins. This model is consistent with ATH’s better bioavailability and more predictable dose response.
Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidinediones
Authors: Leugers Anne , Lohrmann Jens , Ernst Sandra , Sobel Burton , Bode Christoph , Nordt Thomas , Zirlik Andreas
Published: March 2004

Adipose tissue produces substantial amounts of plasminogen activator inhibitor type-1 (PAI-1), an established cardiovascular risk factor. This study evaluated PAI-1 expression in human adipose tissue in response to thiazolidinediones, insulin sensitising drugs activating peroxisome proliferator-activated receptorgamma (PPAR-γ). Troglitazone, rosiglitazone, and ciglitazone significantly reduced PAI-1 protein expression in human preadipocytes under basal conditions and after stimulation of the cells with TGF-β. Pioglitazone had no effect. In human adipocytes all four thiazolidinediones significantly attenuated PAI-1 expression. Signalling appeared to be mediated via PPAR-γ and effects reflected, at least in part, changes in transcription. Accordingly, patients with insulin resistance may benefit from treatment with thiazolidinediones with respect to diminution of PAI-1 expression in adipose tissue and consequent potential reduction of cardiovascular risk.
Orally administered heparins prevent arterial thrombosis in a rat model
Authors: Pinel Cory , M.Wice Sandra , Hiebert Linda
Published: March 2004

Our previous studies demonstrated that orally administered heparins prevent thrombosis in a rat jugular vein thrombosis model, where bovine unfractionated heparin (UFH) and the low molecular weight heparin tinzaparin reduced thrombotic incidence by 50% at 7.5 and 0.1 mg/kg, respectively. Our objectives were to determine if similar antithrombotic effects of oral heparin could be observed in an arterial thrombosis model. In this model, filter paper soaked in 30% ferric chloride was applied to the exposed rat carotid artery. A flowmeter recorded blood flow over a 60 min period determining time when the thrombus began forming (TTB) and time till occlusion (TTO). Immediately following, the thrombus was removed, dried and weighed 24 h later. Bovine UFH (7.5 mg/kg), tinzaparin (0.1 mg/kg) or saline was administered by stomach tube at 2, 5 and 25 h prior to thrombus initiation. TTB was significantly increased when UFH was given at 5 and 25 h but not 2 h prior, and when tinzaparin was given at 5 but not 2 or 25 h prior compared to rats given oral saline. TTO was significantly increased for both UFH and tinzaparin when given 5 and 25 h but not 2 h prior (one-way ANOVA). There was no difference in TTO and TTB between UFH and tinzaparin treated groups. A trend in reduction in thrombus weight was observed for UFH at 5 and 25 h prior and tinzaparin at 5 h prior to thrombus initiation (one-way ANOVA). Although no significant changes were observed in activated partial thromboplastin times, Heptest or anti-Xa activity from plasma of heparin treated rats, endothelial heparin concentrations were significantly greater than controls for UFH at 5 h and for tinzaparin at 2, 5, and 24 h. Thus, heparins administered by the oral route are effective antithrombotic agents in arterial as well as venous models.
Localization of heparin and low-molecular-weight heparin in the rat kidney
Authors: Douros Vivian , Podor Thomas , Shaughnessy Stephen , Weitz Jeffrey , Young Edward
Published: March 2004

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are cleared, at least in part, by the kidneys through a poorly understood process. This study was undertaken to explore the mechanism of renal clearance of these drugs. Rats were given fluorescein-5-isothiocyanate (FITC)-labeled UFH or LMWH intravenously. At intervals after injection, rats were euthanized and the kidneys were harvested and subjected to immunohistochemical analysis and fluorescence microscopy. Both UFH and LMWH were localized to renal tubular cells and no immunoperoxidase staining or fluorescence was detected in glomeruli. Autoradiography demonstrated similar intracellular distribution of radio-labeled UFH suggesting that this phenomenon is independent of the method used to label heparin. Fluoresence in the tubules increased as a function of time after UFH injection, but reached a plateau after LMWH injection suggesting that the rate of renal tubular uptake depends on the molecular size of the heparin. When administered prior to FITC-labeled UFH or LMWH, probenecid, a renal organic anion inhibitor, decreased the renal tubular uptake of the heparins, whereas cimetidine, a renal organic cation inhibitor, had no effect. These findings suggest that renal excretion of UFH and LMWH primarily reflects tubular uptake via an organic anion transport mechanism.
Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk
Authors: Medina Pilar , Navarro Silvia , Estellés Amparo , Vayá Amparo , Woodhams Barry , Mira Yolanda , Villa Piedad , Migaud-Fressart Martine , Ferrando Fernando , Aznar Justo , Bertina Rogier , España Francisco
Published: March 2004

Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma. The distribution of sEPCR levels in healthy populations is bimodal. Previously, we described two polymorphisms in exon 4 of the EPCR gene, 4600A/G that encodes the substitution of Ser219 by Gly in the transmembrane region of EPCR and 4678G/C in the 3’-UT region. The aim of this study was to investigate the relationship between these two polymorphisms and plasma sEPCR and APC levels and risk of venous thrombosis. We genotyped 401 healthy controls from the Spanish population and measured their plasma sEPCR and APC levels. Carriers of the 4600AG genotype had significantly higher sEPCR levels than those with the AA genotype, while the 4678CC genotype was associated, to a lesser extent, with elevated APC levels. To assess the effect of these polymorphisms on the risk of thrombosis, we genotyped 405 patients with venous thromboembolism. The frequency of the 4600AG genotype was very similar in patients and controls (p=0.975), whereas the 4678CC genotype was significantly more frequent in controls than in patients (p=0.008). In multivariate analysis, carriers of the 4678CC genotype had a decreased risk of thrombosis (OR=0.61, p=0.009). These data indicate that individuals carrying the 4600AG genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism.
An enzyme immunoassay of ADAMTS13 distinguishes patients with thrombotic thrombocytopenic purpura from normal individuals and carriers of ADAMTS13 mutations
Authors: Zhou Wenhua , Tsai Han-Mou
Published: March 2004

Recent studies demonstrate that assay of ADAMTS13, a circulating zinc metalloprotease that cleaves von Willebrand factor (VWF) at the Y1605-M1606 bond, is an important tool in the diagnosis of thrombotic thrombocytopenic purpura (TTP). In order to develop a method that could be adapted for general use, we describe an enzyme immunoassay (EIA)-based method for measuring the activity of ADAMTS13 in patient plasma samples. A monomeric peptide consisting of the amino acid residues D1596-R1668 of VWF was produced that spanned the ADAMTS13 cleavage site and was franked by glutathione s-transferase (GST) and a 6His sequences at the amino and carboxyl termini respectively. When probed with either anti-GST or anti-6His, the VWF fragment appeared as a 38.1-kDa band. After incubation with normal plasma, the VWF fragment was replaced by a 30.4-kDa band, which was recognized by antiGST but not by anti-6His, consistent with the expected cleavage at the Y1605-M1606 bond. EDTA or plasma samples from patients with TTP inhibited this cleavage. After incubation with normal plasma, the VWF fusion protein immobilized onto antiGST coated microtiter plate wells lost its anti-6His binding activity in a timeand plasma concentration-dependent manner. By using this EIA, the ADAMTS13 activity level was less than 0.12 U/mL in patients with acquired or hereditary TTP, distinguishing these patients from normal individuals or carriers of one copy of mutant ADAMTS13 allele. These results suggest the EIA method based on the VWF fusion protein is a simple but promising alternative for measuring ADAMTS13 activity.
Evidence of a net release of tissue-type plasminogen activator across the human cerebral vasculature
Authors: Blomstrand Christian , Westerlind Anne , Jern Christina
Published: March 2004

We have earlier described models for measuring local net release rates of tissue-type plasminogen activator (t-PA) in vivo across skeletal, coronary, pulmonary, and splanchnic vascular beds. Aim of the present study was to investigate whether there is a net release of t-PA across the human cerebral vascular bed and whether an acute regulated release can be induced by sympathoadrenal activation. Fourteen male subjects undergoing elective coronary artery bypass grafting were investigated prior to surgery and during sternotomy-induced sympathoadrenal activation. Blood samples were obtained simultaneously from the radial artery and the jugular bulb. Blood flow velocity in the middle cerebral artery (VMCA) was determined by transcranial Doppler. Cerebral net release of t-PA was calculated as the arterio-venous concentration gradient times VMCA. Prior to surgery there was a significant cerebral net release of t-PA (131 and 42 ng/min for t-PA antigen and activity, respectively). The release was significantly induced by sternotomy (to 271 and 80 ng/min, respectively). No significant cerebral net release of plasminogen activator inhibitor type 1 (PAI-1) was detected throughout the experiment. The results show that there is a basal net release of t-PA across the human cerebral vascular bed and that sympathoadrenal activation induces a local regulated release of t-PA.
Beyond cholesterol: the enigma of atherosclerosis revisited
Authors: Lackner Karl , Han Shan-Rui , Torzewski Michael , Husmann Matthias , Bhakdi Sucharit
Published: March 2004

Atherosclerosis is widely regarded as a chronic inflammatory disease that develops as a consequence of entrapment of low density lipoprotein (LDL) in the arterial intima. Native LDL lacks inflammatory properties, so the lipoprotein must undergo biochemical alterations in order to become atherogenic. Modification is commonly regarded as being dangerous because it bestows inflammatory properties onto the lipoprotein. Most current models consider oxidation to be the decisive modifying event. Here, we submit a different concept for discussion. We propose that modification of tissue-entrapped LDL is required because it enables the lipoprotein to signal to the immune system and effect its own removal. Oxidation would be too haphazard to fulfill this function. We summarize the evidence indicating that modification occurs through the action of ubiquitous hydrolytic enzymes. Enzymatically remodeled LDL binds C-reactive protein. C-reactive protein bound to remodeled LDL not only activates complement but also regulates it by inhibiting activation of the terminal complement cascade. Simultaneously, epitopes are exposed to enable the lipoprotein to be recognized and taken up by macrophages. The high density lipoprotein-dependent reverse transport pathway concludes the sequence of events that clear tissues of cholesterol in a non-inflammatory manner very similar to what has been described for the removal of apoptotic cells. It is proposed that these physiological processes occur throughout life without harm, pathology evolving only when the machinery suffers overload. Detrimental effects are then evoked primarily by the unreigned activation of complement, macrophages, and other effectors of the immune system in the lesions.
Different Paradigms for Choosing Sequential Reweighting Algorithms
Authors: Blanchard Gilles
Published: March 2004

Analyses of the success of ensemble methods in classification have pointed out the important role played by the margin distribution function on the training and test sets. While it is acknowledged that one should generally try to achieve high margins on the training set, the more precise shape of the empirical margin distribution function one should favor in practice is subject to different approaches.

We first present two concurrent philosophies for choosing the empirical margin profile: the minimax margin paradigm and the mean and variance paradigm. The best-known representative of the first paradigm is the AdaBoost algorithm, and this philosophy has been shown by several other authors to be closely related to the principle of the support vector machine. We show that the second paradigm is very close in spirit to Fisher's linear discriminant (in a feature space).

We construct two boosting-type algorithms, very similar in their form, dedicated to one or the other philosophy. We consequently derive by interpolation a very simple family of iterative reweighting algorithms that can be understood as different trade-offs between the two paradigms and argue from experiments that this can allow for a suitable adaptivity to different classification problems, particularly in the presence of noise or excessive complexity of the base classifiers.
Time and Uncertainty: A Metaphorical Equation
Authors: Assad Maria
Published: February 2004

My first argument posits that concepts of temporality are discursive strategies to harness uncertainty understood as an innate human condition. Saint Augustine's question of time and some poetic quotes serve as examples to demonstrate the metaphoric use of time in order to attenuate the effects of uncertainty in human affairs. The long history of this substitution is interrupted, however, by Newtonian celestial mechanics, which reduced the metaphoric power of time to quantifiable temporal increments within the construct of differential equations. While classical science continued creating models to explain nature within the conceptual limits of a perfectly reversible and therefore redundant time, poetry, and literature in general, re-discovered the power of time, but through an increasingly radical shift in its relationship to uncertainty. Therefore, using examples from writings by Stéphane Mallarmé and Honoré de Balzac, my second argument explores the possibility that uncertainty is time, not in a metaphoric mode, but as a conceptual identity. Bonding time and uncertainty in this fashion, the examples show further that literary discourse of the 19th Century projects the nonlinear dynamical thinking that dominates late 20th Century scientific debate.
Time and Uncertainty in Elizabeth Bishop's Poems
Authors: Bush Ann Marie
Published: February 2004

Bishop's poems often link the sense of time to specific emotional tones and levels of awareness of varying degrees. In particular, the poems demonstrate not only the forward movement of linear time, but also the merger of present and past to brighten feelings of loss and to provide a sense of security that counters feelings of uncertainty common in a world where change occurs over time. Feelings of anxiety over loss and uncertainty reside in the poems, but at the same time, a positive feeling of well-being (outright joy or peace and solace) surfaces as the speaker intertwines comforting pleasant past moments with her anxious present, making the past and present indistinguishable and creating an unclear sense of time.
"Brain Death," Death, and Personal Identity
Authors: Steineck Christian
Published: February 2004

The issue of brain death touches directly on questions pertaining to our understanding of what it means to be human. Technological progress made possible the sustaining of signs of life in individuals who seem dead to the world. The concept of brain death was introduced to describe this phenomenon, and to answer some of the normative questions that were raised by it. In my article, I approach the problem of brain death with a focus on its temporal aspects. First I sketch out some general features of human life and death in terms of the theories of time of J. T. Fraser and G. Dux. Then I describe and analyze various definitions of brain death and criteria for its testing.The two most important variants are 'whole brain death' as the death of the organism, and 'cerebral death' as the death of the person. I discuss arguments in favor of, and against these concepts and analyze the framework and structuring of temporalities involved in each of them. I conclude that the extant theories in favor of 'brain death' are unsatisfactory, for factual and conceptual reasons. Most importantly, they neglect essential factors of personal identity. Because they employ a naturalistic concept of the human body, they fail to grasp its expressive quality and its function as a medium of communication. Furthermore, they fail to grasp the social dimension of personal identity. Because the concepts of 'brain death' as a criterion for the determination of death fail, we should regard brain-dead people as living human beings, and decide about their treatment accordingly.