Therapeutic evaluation of compounds in the SCID-RA papillomavirus model

A previous study by Kreider (Kreider et al., 1979) indicated that rabbit skin, which had been transplanted to immunodeficient nude mice, could be successfully infected with cottontail rabbit papillomavirus (CRPV). We have extended this observation in developing a rodent model for evaluation of compounds for activity against the papillomaviruses. In this model (called the SCID-Ra model), rabbit ear skin is transplanted to the dorsum of SCID mice and allowed to heal for 3 weeks. Infection with CRPV by scarification leads to the growth of warty lesions within 2 3 weeks in >95% of the animals. Topical and/or systemic therapy can be initiated at various times post infection (PI). Weekly lesion scores are recorded and compounds are evaluated for their ability to suppress wart growth when compared to untreated control mice. Ribavirin, which has had a suppressive effect both in the clinic for the treatment of respiratory papillomatosis and on the growth of warts in the rabbit back model, was evaluated and showed significant anti-proliferative activity with oral dosing. Both antiviral and antiproliferative compounds including podophyllin and 5-fluorouracil, which have been used clinically for the treatment of human papillomavirus (HPV) infections, were evaluated in this model. The anti-mitotic compound, Navelbine (vinorelbine tartrate), which is used for the treatment of non-small cell lung carcinoma was evaluated in this system and showed significant inhibition of wart growth with somewhat less topical cytotoxicity when compared to podophyllotoxin.     

The relationship between preparation convergence and retention of extracoronal retainers

PURPOSE: Although traditional ideal convergence (the sum of taper of the opposite sides) for crown preparation has been arbitrarily set at 4 degrees to 10 degrees, some believe absolute parallelism yields the highest retention. This study examined the relationship between the degree of convergence of a machined metal die and the retention of its casting. MATERIALS AND METHODS: The method used was that of cementing cast metal crowns onto full crown preparations on brass dies with varying convergence angles, and then recording the force required to remove the crowns from the dies in a vertical direction using a Tate-Emery Testing Machine and Load Indicator. RESULTS: It was found that retention (i.e., the force needed to remove the cemented castings from the die in their common long axis) increases from 0 degree convergence to peak between 6 degrees to 12 degrees convergence. It also seems that a critical film thickness does exist for optimum retention, and that film thicknesses smaller than the critical thickness may be responsible for the phenomenon that we have observed and directly related to the convergence angle itself. CONCLUSIONS: There seems to be experimental data supporting the use of traditionally taught convergence. Our study found that convergence angles between 6 degrees and 12 degrees seem to be optimum for tooth crown preparation when one plans to use zinc phosphate cement. Convergence angles of less than 6 degrees may not be desirable even if they can be clinically achieved. The results of our study indicate that a relationship exists between the convergence angle and the critical cement thickness that is necessary to realize the maximum strength properties of zinc phosphate cement.     

Use of Mono Mac 6 human monocytic cell line and J774 murine macrophage cell line in parallel antimycobacterial drug studies

The Mono Mac 6 (MM6) human monocytic cell line was evaluated with the established J774 murine macrophage cell line to ascertain its effectiveness in determining the intracellular activities of antimycobacterial drugs. Cells were infected with Mycobacterium tuberculosis H37Ra and treated with drug concentrations corresponding to the MICs, as well as to threefold higher than and threefold less than the MICs. Changes in CFU were compared after 7 days to determine significant differences between treated and nontreated groups. The results suggest that MM6 will make a useful model for testing the intracellular activities of antituberculosis drugs.     

Different types of signal coupling in the visual cortex related to neural mechanisms of associative Processing and perception

The hypothesis of object representation by synchronization in the visual cortex has been supported by our recent experiments in monkeys. They demonstrated local synchrony among /spl gamma/ activities (30-90 Hz) and their perceptual modulation, according to the rules of figure-ground segregation. However, /spl gamma/-synchrony in primary visual cortex is restricted to few mm, challenging the synchronization hypothesis for larger cortical object representations. The restriction is due to randomly changing phase relations among locally synchronized patches which, however, form continuous waves of /spl gamma/-activity, traveling across object representations. The phase continuity of these waves may support coding of object continuity. Interactions across still larger distances, measured among cortical areas in human data, involve amplitude envelopes of /spl gamma/ signals. Based on models with spiking neurons we discuss potentially underlying mechanisms. Most important for /spl gamma/ synchronization are local facilitatory connections with distance-dependent delays. They also explain the occurrence of /spl gamma/ waves and the restriction of /spl gamma/-synchrony. Fast local feedback inhibition generates /spl gamma/ oscillations and supports local synchrony, while slow shunting inhibitory feedback supports figure-ground segregation. Finally, dispersion in inter-areal far projections destroys coherence of /spl gamma/ signals, but preserves their amplitude modulations. In conclusion, we propose that the hypothesis of associative processing by /spl gamma/ synchronization be extended to more general forms of signal coupling.     

Shortest path algorithms: A computational study with the C programming language

The main purpose of this study is to evaluate the computational efficiency of algorithms for calculating shortest paths when they are correctly coded by using the C programming language. The eight algorithms that we selected for this experiment are the most efficient, either measured in terms of worst-case bounds or marked as such from previous computational studies; they include the redistributive heap algorithm. We suggest computer implementations that use the full power of C. In particular, the network representation and the various data structures used to keep the scan eligible list may be managed by using only additions and no multiplications, while it is not possible with FORTRAN. These capabilities, unique to C, yield several interesting conclusions: one may expect to speed up a shortest path algorithm by a factor of 20%; in some cases, this factor may reach 30%. Interestingly, the level of programming difficulty required to achieve these benefits is not greater than that required by implementations using arrays.     

A new pneumatic bearing dynamometer for power input measurement in stirred tanks

A turntable dynamometer has been constructed for the accurate measurement of power input and mixing applications in bench stirred tank reactors. The main feature of this device is a pneumatic bearing with complementary conical parts. The conical pneumatic bearing permitted to apply eccentric loads without affecting its stability. The static friction torque in the pneumatic bearing was very small, 4 × 10^?4 Nm, and can be neglected in the experimental ranges of measured torques, i.e. from 5 × 10^?3 to 2.21 Nm. In accordance with the instrumentation used, the deviations obtained with the apparatus are less than 10% at low torque readings. At moderate torques, deviations lower than 1% are routinely obtained. Several power input measurements show that the obtained data scatter is lower than 2.5%. The power input response in the turbulent regime is in agreement with dimensional analysis: the power input depends on the cube of the impeller speed. In addition, data obtained with a turbine impeller under ungassed conditions agree with the predictions of a published correlation, which takes into account several geometrical parameters.     

New approaches for error estimation and adaptivity for 2D potential boundary element methods

This work presents two new error estimation approaches for the BEM applied to 2D potential problems. The first approach involves a local error estimator based on a gradient recovery procedure in which the error function is generated from differences between smoothed and non‐smoothed rates of change of boundary variables in the local tangential direction. The second approach involves the external problem formulation and gives both local and global measures of error, depending on a choice of the external evaluation point. These approaches are post‐processing procedures. Both estimators show consistency with mesh refinement and give similar qualitative results. The error estimator using the gradient recovery approach is more general, as this formulation does not rely on an ‘optimal’ choice of an external parameter. This work presents also the use of a local error estimator in an adaptive mesh refinement procedure. This r‐refinement approach is based on the minimization of the standard deviation of the local error estimate. A non‐linear programming procedure using a feasible‐point method is employed using Lagrange multipliers and a set of active constraints. The optimization procedure produces finer meshes close to a singularity and results that are consistent with the problem physics. Copyright © 2002 John Wiley & Sons, Ltd.     

Nisin expression production from Lactococcus lactis in milk whey medium

BACKGROUND: Nisin is a commercially available bacteriocin produced by Lactococcus lactis ATCC 11454 and used as a natural agent in the biopreservation of food. In the current investigation, milk whey, a byproduct from dairy industries was used as a fermentation substrate for the production of nisin. Lactococcus lactis ATCC 11454 was developed in a rotary shaker (30 °C/36 h/100 rpm) using two different media with milk whey (i) without filtration, pH 6.8, adjusted with NaOH 2 mol L^?1 and without pH adjustment, both autoclaved at 121 °C for 30 min, and (ii) filtrated (1.20 µm and 0.22 µm membrane filter). These cultures were transferred five times using 5 mL aliquots of broth culture for every new volume of the respective media. RESULTS: The results showed that culture media composed of milk whey without filtration supplied L. lactis its adaptation needs better than filtrated milk whey. Nisin titers, in milk whey without filtration (pH adjusted), was 11120.13 mg L^?1 in the second transfer, and up to 1628‐fold higher than the filtrated milk whey, 6.83 mg.L^?1 obtained in the first^t transfer. CONCLUSIONS: Biological processing of milk byproducts (milk whey) can be considered a profitable alternative, generating high‐value bioproducts and contributing to decreasing river disposals by dairy industries. Copyright © 2008 Society of Chemical Industry     

Serotonin-4 receptor antagonists reverse cocaine-induced cardiac arrhythmia

CONTEXT: Adolescent smoking prevalence is tracked annually and has increased since 1991. In contrast, little is known about trends in smoking among college students, a group that has previously been more resistant to tobacco use than other young adults. OBJECTIVE: To examine changes in cigarette smoking among college students between 1993 and 1997 and among different types of students and colleges. DESIGN: Self-administered survey (Harvard School of Public Health College Alcohol Study). SETTING: One hundred sixteen nationally representative 4-year colleges. SUBJECTS: A total of 15103 randomly selected students in 1993 (70% response rate) and 14251 students in 1997 (60% response rate). MAIN OUTCOME MEASURES: Self-reports of cigarette smoking in the past 30 days and in the past year, age at smoking first cigarette, and number of attempts to quit. RESULTS: Over 4 years, the prevalence of current (30-day) cigarette smoking rose by 27.8%, from 22.3% to 28.5% (P<.001). The increase was observed in 99 of 116 colleges and was statistically significant (P<.05) in 27 (23%) of them. Current smoking increased across all student subgroups (defined by sex, race/ethnicity, and year in school) and in all types of colleges. Smoking is rising faster in public schools (from 22.0% to 29.3%) than in private schools (from 22.9% to 26.8%). Eleven percent of college smokers had their first cigarette and 28% began to smoke regularly at or after age 19 years, by which time most were already in college. Half of current smokers tried to quit in the previous year; 18% had made 5 or more attempts to quit. CONCLUSIONS: Cigarette use is increasing on campuses nationwide in all subgroups and types of colleges. Substantial numbers of college students are both starting to smoke regularly and trying to stop. National efforts to reduce smoking should be extended to college students.