Scatterer properties like the average effective scatterer diameter and acoustic concentration were determined in vivo using a quantitative ultrasound (QUS) technique from two tumor phenotypes grown ...in animal models. These tumor models included spontaneously occurring mammary fibroadenomas in rats and transplanted 4T1 mammary carcinomas in mice. The scatterer properties of average scatterer diameter and acoustic concentration were estimated using a Gaussian form factor from the backscattered ultrasound measured from both types of tumors. QUS images of the tumors were constructed utilizing estimated scatterer properties from regions in the tumors. The QUS images showed a clear distinction between the two types of tumors and a statistically significant difference existed between their estimated scatterer properties. The average scatterer diameter and acoustic concentration for the mammary fibroadenomas were estimated to be 105/spl plusmn/25 /spl mu/m and -15.6/spl plusmn/5 dB (mm/sup -3/), respectively. The average scatterer diameter and acoustic concentration for the carcinomas was estimated to be 28/spl plusmn/4.6 /spl mu/m and 10.6/spl plusmn/6.9 dB (mm/sup -3/), respectively. The distinctions in the scattering properties are clearly seen in the QUS images of the tumors and indicate that QUS imaging can be useful in differentiating between different types of mammary tumors.
Human figures have been animated using a variety of geometric models, including stick figures, polygonal models and NURBS-based models with muscles, flexible skin or clothing. This paper reports on ...experimental results indicating that a viewer's perception of motion characteristics is affected by the geometric model used for rendering. Subjects were shown a series of paired motion sequences and asked if the two motions in each pair were the same or different. The motion sequences in each pair were rendered using the same geometric model. For the three types of motion variation tested, sensitivity scores indicate that subjects were better able to observe changes with the polygonal model than they were with the stick-figure model.
Age-dependent threshold and superthreshold behavior of ultrasound-induced lung hemorrhage were investigated with 116 2.1 /spl plusmn/ 0.3-kg neonate crossbred pigs (4.9 /spl plusmn/ 1.6 days old), ...103 10 /spl plusmn/ 1.1-kg crossbred pigs (39 /spl plusmn/ 5 days old), and 104 20 /spl plusmn/ 1.2-kg crossbred pigs (58 /spl plusmn/ 5 days old). Exposure conditions were: 3.1 MHz, 10-s exposure duration, 1-kHz pulse repetition frequency (PRF), and 1.2-/spl mu/s pulse duration. The in situ (at the pleural surface) peak rarefactional pressure ranged between 2.2 and 10.4 MPa with either eight or nine acoustic pressure groups for each of the three pig ages (12 pigs/exposure group) plus sham exposed pigs. There were no lesions in the shams. Pigs were exposed bilaterally with the order of exposure (left then right lung, or right then left lung) and acoustic pressure both randomized. Pig age was not randomized. Individuals involved in animal handling, exposure, and lesion scoring were blinded to the exposure condition. Logistic regression analysis was used to examine the dependence of the lesion incidence rates on in situ peak rarefactional pressure, left versus right lung exposure, order of exposure (first versus second), and age in three age groups. Likewise, lesion depth and lesion root surface area were analyzed using Gaussian tobit regression analysis. A significant threshold effect on lesion occurrence was observed as a function of age; younger pigs were less susceptible to lung damage given equivalent in situ exposure. Overall, the oldest pigs had a significantly lower threshold (2.87 /spl plusmn/ 0.29 MPa) than middle-aged pigs (5.83 /spl plusmn/ 0.52 MPa). The oldest pigs also had a lower threshold than neonate pigs (3.60 /spl plusmn/ 0.44 MPa). Also, an unexpected result was observed. The ultrasound exposures were bilateral, and the threshold results reported above were based on the lung that was first exposed. After the first lung was exposed, the pig was turned over and the other lung was exposed to the same acoustic pressure. There was a significant decrease (greater than the confidence limits) in occurrence thresholds: 3.60 to 2.68, 5.83 to 2.97, and 2.87 to 1.16 MPa for neonates, middle-aged, and oldest pigs, respectively, in the second lung exposed. Thus, a subtle effect in lung physiology resulted in a major effect on lesion thresholds.
Attenuation coefficient and propagation speed of intercostal tissues were estimated as functions of temperature (22, 30, and 37/spl deg/C) from fresh chest walls from eight 10- to 11-week-old female ...Sprague-Dawley (SD) rats, eight 21to 24-week-old female Long-Evans (LE) rats, and ten 6- to 10-week-old mixed sex Yorkshire (York) pigs. The primary purpose of the study was to estimate the temperature dependence of the intercostal tissue's attenuation coefficient so that accurate estimates of the in situ (at the pleural surface) acoustic pressure levels could be made for our ultrasound-induced lung hemorrhage studies. The attenuation coefficient of intercostal tissue for both species was independent of the temperature at the discrete frequencies of 3.1 MHz (-0.0076, 0.0065, and 0.016 dB/cm//spl deg/C for SD rats, LE rats, and York pigs, respectively) and 6.2 MHz (-0.015, 0.014, and 0.014 dB/cm//spl deg/C for SD rats, LE rats, and York pigs, respectively). However, the temperature-dependent regressions yielded a significant temperature dependency of the intercostal tissue attenuation coefficients in SD and LE rats (over the 3.1 to 9.6 MHz frequency range); there was no temperature dependency in York pigs (over the 3.1 to 8.6 MHz frequency range). There was no significant temperature dependency of the intercostal tissue propagation speed in SD rats; there was a temperature dependency in LE rats and York pigs (-0.59, -1.6, and -2.9 m/s//spl deg/C for SD rats, LE rats, and York pigs, respectively). Even though the attenuation coefficient's temperature dependency was significant from the linear regression functions, the differences were not very great (-0.040 to -0.13, 0.011 to 0.18, and 0.055 to 0.10 dB/cm//spl deg/C for SD rats, LE rats, and York pigs, respectively, over the data frequency range). These findings suggest that it is not necessary to determine the attenuation coefficient of intercostal tissue at body temperature (37/spl deg/C), but rather it is sufficient to determine the attenuation coefficient at room temperature (22/spl deg/C), a much easier experimental procedure.
It is well documented that ultrasound-induced lung hemorrhage can occur in mice, rats, rabbits, pigs, and monkeys. The objective of this study was to assess the role of the ultrasound beamwidth (beam ...diameter incident on the lung surface) on lesion threshold and size. A total of 144 rats were randomly exposed to pulsed ultrasound at three exposure levels and four beamwidths (12 rats per group). The three in situ peak rarefactional pressures were about 5, 7.5, and 10 MPa. The four 19-mm-diameter focused transducers had measured pulse-echo -6-dB focal beamwidths of 470 /spl mu/m (2.8 MHz; f/1), 930 /spl mu/m (2.8 MHz; f/2), 310 /spl mu/m (5.6 MHz; f/1), and 510 /spl mu/m (5.6 MHz; f/2). Exposure durations were 10 s, pulse repetition frequencies were 1 kHz, and pulse durations were 1.3 /spl mu/s (2.8 MHz; f/1), 1.2 /spl mu/s (2.8 MHz; f/2), 0.8 /spl mu/s (5.6 MHz; f/1) and 1.1 /spl mu/s (5.6 MHz; f/2). The lesion surface area and depth were measured for each rat as well as the percentage of rats with lesions per group. Logistic regression analysis and Gaussian-Tobit analysis methods were used to analyze the data. The effects of in situ peak rarefactional pressure and beamwidth were highly significant, but ultrasonic frequency was not significant. In addition, the estimated interaction between in situ peak rarefactional pressure and beamwidth was positive and highly significant. The ultrasound beamwidth incident on the lung surface was shown to strongly affect the percentage and size of ultrasound-induced lung hemorrhage lesions. Even though ultrasonic frequency was an experimental variable, it was not shown to affect the lesion percentage or size.
Attenuation coefficients of intercostal tissues were estimated from chest walls removed postmortem (pm) from 41 6-to-7-week-old female ICR mice and 27 10-to-11-week-old female Sprague-Dawley rats. ...These values were determined from measurements through the intercostal tissues, from the surface of the skin to the parietal pleura. Mouse chest walls were sealed in plastic wrap and stored at 4/spl deg/C until evaluated, and rat chest walls were sealed in sandwich bags and stored at -15/spl deg/C. When evaluated, chest wall storage time ranged between 1 and 2 days pm for mice and between 41 and 110 days pm for rats. All chest walls were allowed to equilibrate to 22/spl deg/C in a water bath prior to evaluation. For both mouse and rat intercostal tissues, the estimated frequency normalized attenuation coefficient was 1.1 dB/cm-MHz. In order to determine if there was an effect of storage time on estimates of attenuation coefficient, an independent experiment was conducted. The intercostal tissues from six mouse chest walls were evaluated at three time points (1, 22, and 144 days pm), and from six rat chest walls were evaluated at four time points (1, 22, 50, and 125 days pm). There was no difference in the estimated intercostal tissue attenuation coefficient as a function of time postmortem.
Attention coefficient and propagation speed of intercostal tissues were estimated from chest walls removed postmortem (pm) from 15 5.3 /spl plusmn/ 2.3-day-old, 19 31 /spl plusmn/ 6-day-old, and 15 ...61 /spl plusmn/ 3-day-old crossbred pigs. These ultrasonic propagation properties were determined from measurements through the intercostal tissues, from the surface of the skin to the parietal pleura. The chest walls were placed in a 0.9% sodium chloride solution, sealed in freezer bags, and stored at -15/spl deg/C prior to measurements. When evaluated, chest-wall storage time ranged between 1 and 477 days pm. All chest walls were allowed to equilibrate to 22/spl deg/C in a water bath prior to evaluation. There was an age dependency of the intercostal tissue propagation speed, with the speed increasing with increasing age. The attenuation coefficient of intercostal tissue was shown to be independent of the age of the pig at the discrete frequencies of 3.1 and 6.2 MHz. For pig intercostal tissues, the estimated attenuation coefficient over the 3.1-9.2 MHz frequency range was A = 1.94f/sup 0.90/ where A is in decibels per centimeter (dB/cm) and f is the ultrasonic frequency in megahertz. In order to determine if there was an effect of storage time pm on estimates of attenuation coefficient, a second experiment was conducted. Five of the youngest pig chest walls measured on day 1 pm in the first experiment were stored at 4/spl deg/C prior to the first evaluation then stored at -15/spl deg/C before being measured again at 108 days pm. There was no difference in the estimated intercostal tissue attenuation coefficient as a function of storage time pm.
It is suggested that the cosmological speculation of Pierre Teilhard de Chardin (eg, see The Phenomenon of Man, 2nd edition Tr from French, New York: Harper & Row, 1965 1955) is a valuable basis for ...an environmental ethics that perceives individual natural objects as good in themselves, & the world as good in itself. Teilhard perceives man as fundamentally part of a cosmic environmental whole that is greater than mankind taken individually or collectively. It is argued that his holistic views on human biological & psychological & social evolution are compatible with a biocentric environmental ethics. Teilhard's views are compared with those of the deep ecology movement, & it is shown that Teilhard's hierarchical system is not humanistically oriented in a way that need be interpreted by Teilhardians as contrary to environmental well-being. It is argued that Teilhard's sympathies toward transportation technology, including the automobile, can be interpreted in his holistic manner. It is concluded that Teilhard's theocentric views are also a basis for supporting an environmental ethics that is optimistic but not anthropocentric. HA
The principal motivation of the study was to assess experimentally the question: "Is the MI (Mechanical Index) an equivalent or better indicator of nonthermal bioeffect risk than I/sub SPPA.3/ ...(derated spatial peak, pulse average intensity)?". To evaluate this question, the experimental design consisted of a reproducible biological effect in order to provide a quantitative assessment of the effect. The specific biological effect used was lung damage and the species chosen was the rabbit. This work was initiated, in part, by a study in which lung hemorrhage was observed in 7-week old C3H mice for diagnostic-type, pulsed-wave ultrasound exposures, and, therefore, 6- to 7-week old C3H mice were used in this study as positive controls. Forty-seven adult New Zealand White male rabbits were exposed to a wide range of ultrasound amplitude conditions at center frequencies of 3 and 6 MHz with all temporal exposure variables held constant. A calibrated, commercial diagnostic ultrasound system was used as the ultrasound source with output levels exceeding, in some cases, permissible FDA levels. The MI was shown to be at least an equivalent, and in some cases, a better indicator of rabbit lung damage than either the I/sub SPPA.3/ or p/sub r.3/ (derated peak rarefactional pressure), thus answering the posed question positively. Further, in situ exposure conditions were estimated at the lung pleural surface (PS); the estimated in situ I/sub SPPA.PS/ and p/sub r.PS/ exposure conditions tracked lung damage no better than I/sub SPPA.3/ and p/sub r.3/, respectively, whereas the estimated in situ MI/sub PS/ exposure condition was a slightly poorer predictor of lung damage than MI. Finally, the lungs of six adult crossbred pigs were exposed at the highest amplitude exposure levels permitted by a diagnostic ultrasound system (to prevent probe damage) at both frequencies; no lung damage was observed which suggests the possibility of a species dependency biological effect.
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. ...PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
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