Alternative Granulation Technique: Melt Granulation

A melt granulation process has been investigated (1, 2) which efficiently agglomerates pharmaceutical powders for use in both immediate- and sustained-release solid dosage forms. The process utilizes materials that are effective as granulating fluids when they are in the molten state. Cooling of the agglomerated powders and the resultant solidification of the molten materials completes the granulation process. Both the molten agglomeration and cooling solidification were accomplished in a high shear Collette Gral mixer equipped with a jacketed bowl. Hence, the melt granulation process replaces the conventional granulation and drying operations which use water or alcohol solutions. The melt granulation process has been investigated using immediate- and sustained-release TAVIST® (clemastine fumarate USP) tablet formulations. The TAVIST granulations have been characterized by power consumption monitoring, measurement of the granulation particle size distribution, bulk and tapped density determinations, and loss-on-drying measurements. Scale-up of the melt granulation process for the sustained release TAVIST tablet formulation was judged successful based on a comparison of the hardness, friability, weight uniformity during compression, disintegration time, and dissolution rate data obtained at different manufacturing scales.     

Dielectric behaviour of glasses and glass ceramics in the system BaO-PbO-TiO2-B2O3-SiO2

Glasses with varying molar ratios of PbO/BaO in the system BaO-PbO-TiO₂-B₂O₃-SiO₂ were prepared keeping (BaO + PbO)/TiO₂ ratio equal to one. The glasses were ceramized by two-stage heat treatment. X-ray diffraction indicates that PbTiO₃ crystallizes in lead-rich glasses while BaTiO₃ precipitates in barium-rich compositions. Solid solution (Ba, Pb)TiO₃ does not seem to crystallize over the entire range of compositions. Simultaneous presence of PbO and BaO in the initial glass composition reduces the yield of ferroelectric phase. Dielectric properties have been interpreted in terms of microstructural features.     

Modeling Microwave Vacuum Drying Kinetics and Moisture Diffusivity of Carrot Slices

Carrot slices of 3.5 mm thickness were dried in a laboratory microwave vacuum dryer at five different microwave power density levels of 2, 4.66, 7.33, 10, and 12.66 W/g and at three vacuum chamber pressure levels of 6.66, 19.98, and 33.3 kPa to 4-6% d.b. moisture content. Inside the dryer the sample holding plate was rotated with the speed of 4 rpm for uniform microwaves application. The drying rates were increased with the increase in microwave power density at all pressure levels and the Page model was found to be the most suitable model to predict the drying behavior of carrot slices at all process conditions. The Page model drying rate constant (k, min^-1) showed high correlation with microwave power density at constant pressure by a power law equation and showed a logarithmic relationship with the microwave power density and pressure. Similar to the drying rate constant, the average moisture diffusivity at constant pressure was found to be function of microwave power density by power law equation as well as was also dependent on the power density and pressure by a logarithmic relationship.     

Establishment of human parotid pleomorphic adenoma cells in culture: morphological and biochemical characterization

This study reports the establishment of alpha-amylase-producing human parotid pleomorphic adenoma cell lines (2HP and 2HP1) which have been maintained in culture for over 1 yr. The procedures required preparation of cellular clumps from tumor tissue and plating them on plasma clot or precoated dishes. During the initial phase of growth they required modified MCDB-153 medium without serum. When cells showed signs of degeneration they were changed to MCDB-153 medium containing first 2% and then 10% heat inactivated fetal bovine serum. Although cells grew well in MCDB-153 containing 10% serum, the epithelial cell morphology was not distinct. Therefore, the growth and morphology of cells grown in MCDB-10% serum were compared with those in RPMI growth medium containing 10% fetal bovine serum and F12 containing 10% agammaglobulin newborn bovine serum. Although the growth of cells was a little slower in F12 medium than those in MCDB and RPMI, the epithelial cell morphology was maintained better than in other growth media. The cells of 2HP and 2HP1 produce low levels of alpha-amylase and relatively high levels of alpha-amylase mRNAs of 1176 and 702 bp and contain neurofilament-160, a neuronal-specific marker. The cells of 2HP1 are tumorigenic when tested in athymic mice, but the cells of 2HP are not. The establishment of amylase-producing human parotid adenoma cell lines of different characteristics in culture provides a new opportunity to study the mechanisms of differentiation and transformation, and regulation of alpha-amylase in these cells.     

Mobilization of lead by calcium versenate and dimercaptosuccinate in the rat

1. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) individually and in permutation-combination in various doses (0.1, 0.2 and 0.4 mmol/kg bodyweight) were investigated for their efficacy to mobilize lead from vital tissues into urine and faeces and to restore the lead-sensitive biochemical parameters in lead pre-exposed rats with a view to develop the most acceptable treatment regimen for lead poisoning with a minimal loss of endogenous essential elements. 2. The combined therapy was more effective than a single chelator treatment. 3. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA caused a lower depletion of zinc, calcium and iron but possessed almost equal capability to that of 0.4 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA to produce urinary as well as faecal excretion of lead, to reduce the tissue burden of lead, including that of the brain, and to reverse lead-induced biochemical alterations. 4. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA has shown a definite improvement over previously reported combinations in terms of removal of lead from tissues, particularly the brain, restoration of urinary delta-aminolevulinic acid levels and a decrease in the loss of body zinc and is, therefore, recommended for the treatment of lead intoxication.     

An atomic model of the outer layer of the bluetongue virus core derived from X-ray crystallography and electron cryomicroscopy

BACKGROUND: Bluetongue virus (BTV), which belongs to the Reoviridae family and orbivirus genus, is a non-enveloped, icosahedral, double-stranded RNA virus. Several protein layers enclose its genome; upon cell entry the outer layer is stripped away leaving a core, the surface of which is composed of VP7. The structure of the trimeric VP7 molecule has previously been determined using X-ray crystallography. The articulated VP7 subunit consists of two domains, one which is largely alpha-helical and the other, smaller domain, is a beta barrel with jelly-roll topology. The relative orientations of these two domains vary in different crystal forms. The structure of VP7 and the organizations of 780 subunits of this molecule in the core of virus is central to the assembly and function of BTV. RESULTS: A 23 A resolution map of the core, determined using electron cryomicroscopy (cryoEM) data, reveals that the 260 trimers of VP7 are organized on a rather precise T = 13 laevo icosahedral lattice, in accordance with the theory of quasi-equivalence. The VP7 layer occupies a shell that is between 260 A and 345 A from the centre of the core. Below this radius (230-260 A) lies the T = 1 layer of 120 molecules of VP3. By fitting the X-ray structure of an individual VP7 trimer onto the cryoEM BTV core structure, we have generated an atomic model of the VP7 layer of BTV. This demonstrates that one of the molecular structures seen in crystals of the isolated VP7 corresponds to the in vivo conformation of the molecule in the core. CONCLUSIONS: The beta-barrel domains of VP7 are external to the core and interact with protein in the outer layer of the mature virion. The lower, alpha-helical domains of VP7 interact with VP3 molecules which form the inner layer of the BTV core. Adjacent VP7 trimer-trimer interactions in the T = 13 layer are mediated principally through well-defined regions in the broader lower domains, to form a structure that conforms well with that expected from the theory of quasi-equivalence with no significant conformational changes within the individual trimers. The VP3 layer determines the particle size and forms a rather smooth surface upon which the two-dimensional lattice of VP7 trimers is laid down.     

Quantifying DNS namespace influence

Name resolution using the Domain Name System (DNS) is integral to today’s Internet. The resolution of a domain name is often dependent on namespace outside the control of the domain’s owner. In this article we review the DNS protocol and several DNS server implementations. Based on our examination, we propose a formal model for analyzing the name dependencies inherent in DNS. Using our name dependency model we derive metrics to quantify the extent to which domain names affect other domain names. It is found that under certain conditions, more than half of the queries for a domain name are influenced by namespaces not expressly configured by administrators. This result serves to quantify the degree of vulnerability of DNS due to dependencies that administrators are unaware of. When we apply metrics from our model to production DNS data, we show that the set of domains whose resolution affects a given domain name is much smaller than previously thought. However, behaviors such as using cached addresses for querying authoritative servers and chaining domain name aliases increase the number and diversity of influential domains, thereby making the DNS infrastructure more vulnerable.     

Vector-extrapolated fast maximum likelihood estimation algorithms for emission tomography

A new class of fast maximum-likelihood estimation (MLE) algorithms for emission computed tomography (ECT) is developed. In these cyclic iterative algorithms, vector extrapolation techniques are integrated with the iterations in gradient-based MLE algorithms, with the objective of accelerating the convergence of the base iterations. This results in a substantial reduction in the effective number of base iterations required for obtaining an emission density estimate of specified quality. The mathematical theory behind the minimal polynomial and reduced rank vector extrapolation techniques, in the context of emission tomography, is presented. These extrapolation techniques are implemented in a positron emission tomography system. The new algorithms are evaluated using computer experiments, with measurements taken from simulated phantoms. It is shown that, with minimal additional computations, the proposed approach results in substantial improvement in reconstruction.     

Parallel heap: An optimal parallel priority queue

We describe a new parallel data structure, namely parallel heap, for exclusive-read exclusive-write parallel random access machines. To our knowledge, it is the first such data structure to efficiently implement a truly parallel priority queue based on a heap structure. Employing p processors, the parallel heap allows deletions of (p) highest priority items and insertions of (p) new items, each in O(log n) time, where n is the size of the parallel heap. Furthermore, it can efficiently utilize processors in the range 1 through n.This work was supported by U.S. Army's PM-TRADE contract N61339-88-g-0002, Florida High Technology and Industry grant 11-28-716, and Georgia State University's internal research support during spring and summer quarters, 1991.