Sterile Filtration of NanoCrystal™ Drug Formulations

A Nano Crystal^TM dispersion of the iodinated x-ray contrast agent iodipamide was prepared by wet milling the drug substance in the presence of Pluronic® F127 stabilizer. The mean particle size of the formulation was 98 nm and all drug particles in the formulation were smaller than 220 nm as determined by dynamic light scattering. Approximately 1 liter of dispersion was filtered through a sterile 0.2-μm disposable capsule filter (Supor® 200 DCF^TM, 0.I m² effective filtration area [EFA], Gelman Sciences) to condition the capsule. No drug concentration or size distribution changes were detected after the filtration process. The microbiological validation tests were performed using Pseudomonas diminuta organisms to challenge the capsule under simulated worst-case process conditions. The results showed that the Supor 200 DCF was able to retain 100% Pseudomonas diminuta organisms (≥10⁷ organisms per cm² of effective filtration area). Thus, this study demonstrated that terminal filtration is a feasible process to sterilize Nano Crystal^TM drug dispersions that may be chemically or physically unstable at elevated temperatures and thus not amenable to terminal heat sterilization.     

Graded-index-rod external coupled-cavity laser with backface output-monitor-stabilized single-frequency operation

We have demonstrated a graded-index-rod external coupled-cavity (GRECC) laser with backface output through a partially transmitting external cavity mirror. Laser output is monitored from the backface in a transmitter module with double-loop feedback control which stabilizes output power and maintains single-frequency operation under CW and pseudorandom pulse modulation.     

Building phonotactic knowledge in bilinguals: Role of early exposure.

Timing and amount of exposure to a 2nd language in the acquisition of phonotactic restrictions was examined in 4 experiments. In Experiments 1 and 2, 10-month-old monolingual and bilingual Catalan-Spanish infants were presented with nonwords that were phonotactically legal or illegal in Catalan and phonotactically illegal in Spanish. Differences between the 4 groups of infants were obtained as a function of language dominance. In Experiments 3 and 4, adult Spanish-Catalan bilinguals were compared with the same materials. Catalan-dominant bilinguals were more accurate than Spanish-dominant bilinguals in their perception of legal sequences; however, they were not more accurate with illegal sequences. The findings suggest a complex correlation between the pattern of preference and the amount and timing of exposure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Secreted production of a custom-designed, highly hydrophilic gelatin in Pichia pastoris

A custom-designed, highly hydrophilic gelatin was produced in Pichia pastoris . Secreted production levels in single-copytransformants were in the range 3–6 g/l of clarified brothand purification to near homogeneity could be accomplished bydifferential ammonium sulfate precipitation. Despite the factthat gelatins are highly susceptible to proteolysis becauseof their unfolded structure, the recombinant protein was shownto be fully intact by SDS–PAGE, N-terminal sequencing,gel filtration chromatography and mass spectrometry. Owing toits highly hydrophilic nature, the migration of the syntheticgelatin in SDS–PAGE was severely delayed. Esterificationof the carboxylic amino acid side chains resulted in normalmigration. The high polarity of the synthetic gelatin also accountsfor its negligible surface activity in water at concentrationsup to 5% (w/v), as determined by tensiometry. Circular dichroismspectrometry showed that the non-hydroxylated gelatin did notform triple helices at 4°C. The spectrum was even more representativeof the random coil conformation than the spectrum of naturalnon-hydroxylated gelatins.     

Differences in microbial activity of digesta from three sections of the porcine large intestine according to in vitro fermentation of carbohydrate‐rich substrates

To determine whether faecal microorganisms can represent the entire large intestinal population, samples from caecum, mid‐colon and rectum of three adult pigs were used for the in vitro fermentation of fructo‐oligosaccharide (FOS), potato starch, wheat bran and oat hulls. The cumulative gas production technique measured fermentation kinetics and end‐products such as total gas, NH₃ and volatile fatty acids (VFA). There were significant differences in the fermentability of substrates, in terms of both kinetics and end‐products. More relevant to this study, there were also differences between pigs in respect of total gas production, the rate of gas production (R_M) and VFA production. For large intestine sections, there were more VFA from mid‐colon and rectal inocula compared with that from the caecum (p < 0.0001). Total gas, R_M and NH₃ were highest for rectal, intermediate for mid‐colon and lowest for caecal inocula (p < 0.0001). It was concluded that, while faecal sampling might overestimate caecal fermentation, its use is valid for in vitro assessment of large intestinal fermentation. However, differences between pigs indicate that a mix of samples from several animals remains important. Copyright © 2004 Society of Chemical Industry     

Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in human esophageal cancer in Linxian, China

Esophageal transit scintigraphy seems to be a valid methodology to assess impaired esophageal motility in early stages of disease. The purpose of this study was to discriminate patients with primary Raynaud's phenomenon (RP) and patients with systemic sclerosis (SSc) from healthy subjects by esophageal scintigraphy with a semisolid meal. METHODS: We studied 32 patients with primary RP, 18 with SSc and 13 healthy subjects. Dysphagia, acid regurgitation and heartburn were scored. After an overnight fast, all subjects underwent esophageal scintigraphy, using a semisolid orally ingested bolus (10 mL apple puree) labeled with 99mTc-sulfur colloid. Esophageal transit and emptying time and integral value were evaluated with the subjects in the upright (sitting) and supine positions. Transit time was defined as the time from the entry of 50% of radioactivity into the upper esophagus until the clearance of 50% of the bolus from the whole esophagus. Emptying time was defined as the time from the entry of 50% of radioactivity into the upper esophagus, until the clearance of 100% of the bolus from the whole esophagus. Integral value was defined as the total counts under the time-activity curve normalized to the maximum. RESULTS: Esophageal transit and emptying time and integral value, evaluated in both positions, were significantly higher in patients with SSc than in healthy subjects and than in patients with RP. Moreover, patients with RP had all three parameters, assessed in supine position, significantly longer compared to healthy subjects. Clinical scores regarding dysphagia, acid regurgitation and heartburn were not significantly different between patients with RP and SSc. CONCLUSION: Esophageal transit and emptying time and integral value appear to be able to discriminate patients with primary RP from patients with SSc and patients with RP from healthy subjects, suggesting an early mild esophageal dysfunction in RP.     

Stakeholder ranking of watershed goals with the vector analytic hierarchy process: Effects of participant grouping scenarios

More effective methods of eliciting and summarizing stakeholders' goals can assist in improving watershed management. This paper discusses the process of summarizing the goals that were generated during a workshop of watershed stakeholders in Virginia by using the Vector Analytic Hierarchy Process, and then grouping them into homogeneous subgroups by using two different methods: 1) assigning subgroups based on individuals' stated affiliations from a participant bio-sheet; and 2) assigning subgroups based on the similarity of individuals' actual preferences between the goals. Several different clustering approaches are considered for creating the preference-based subgroups, and the relative advantages and disadvantages of each approach are discussed. The process of combining the subgroups to generate a single overall preference structure for the group as a whole is also considered, and the final results are compared based on both the resulting rankings and the coherence, or variability of opinion, that they reflect. Determining the “best” set of subgroups can be valuable not only in exploring the underlying nature of the population's preferences, but also in supporting additional discussion and analysis of the results. As such, it can ultimately lead to much stronger and better informed decision-making by the stakeholders.     

Distribution of mono‐ and di‐methacrylic monomers in SBS block copolymer and its influence on the photopolymerization process

Persoz hardness measurements and the analysis of the temperature dependence of the storage modulus (E′) for SBS di‐ and tetrafunctional methacrylic monomer systems were carried out to determine the distribution of the monomers in the domains or phases of the SBS block copolymer, as well as the aggregation state of each system. The forces of attraction between the monomer and the phases or domains in the matrix (similar solubility parameters with appreciable dipole‐dipole and hydrogen bonding interactions) were determinant as for the monomer distribution. The influence of these structural factors on the kinetic parameters of the photoinitiated polymerization of di‐ and tetrafunctional methacrylic monomers in the SBS matrix was studied. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 163–168, 2005