Showing papers by "Research Triangle Park published in 1989"

Combinational profiles of sequential benchmark circuits

Abstract: A set of 31 digital sequential circuits described at the gate level is presented. These circuits extend the size and complexity of the ISCAS'85 set of combinational circuits and can serve as benchmarks for researchers interested in sequential test generation, scan-based test generation, and mixed sequential/scan-based test generation using partial scan techniques. Although all the benchmark circuits are sequential, synchronous, and use only D-type flip-flops, additional interior faults and asynchronous behavior can be introduced by substituting for some or all of the flip-flops their appropriate functional models. The standard functional model of the D flip-flop provides a reference point that is independent of the faults particular to the flip-flop implementation. A testability profile of the benchmarks in the full-scan-mode configuration is discussed. >

The purine path to chemotherapy

Abstract: Research on antimetabolites of nucleic acid purines led to drugs for the treatment of acute leukemia (6-mercaptopurine and thioguanine), gout and hyperuricemia (allopurinol), and herpesvirus infections (acyclovir), and for the prevention of organ transplant rejection (azathioprine).

A Fluorescent Indicator for Measuring Cytosolic Free Magnesium

Abstract: The previously developed chelator O-aminophenol-N,N,O-triacetic acid (APTRA) (L. A. Levy, E. Murphy, B. Raju, and R. E. London. Biochemistry 27: 4041-4048, 1988) has been modified to yield a fluorescent analogue which can be utilized as an intracellular probe for ionized Mg2+. The fluorescent analogue, FURAPTRA, with a magnesium dissociation constant of 1.5 mM, is structurally analogous to the calcium chelator fura-2 and exhibits a similar excitation shift on magnesium complexation. Hence, data on the intracellular Mg2+ concentration can be obtained using an analogous ratio method. The acetoxymethyl form of the chelator is readily loaded into cells and has been used to determine a cytosolic free Mg2+ concentration of 0.59 mM for isolated rat hepatocytes. As a consequence of the relatively high levels of cytosolic Mg2+, the problem of ion buffering is much less severe than for the analogous calcium indicators.

Gulf of Mexico hydrocarbon seep communities

Abstract: Sediment and water samples were collected by submersible in September 1986 at 16 locations on the carbonate cap overlying a conical diapir, which was formed by the upward migration of oil and gas through a subsurface fault on the continental slope off Louisiana, USA (27°47′N; 91°30.4′W). The biological community at the site was photographed quantitatively with still and video cameras. Rigorous spatial sampling indices were maintained so that variation in chemical parameters and in the abundance of photographed organisms could be estimated within the bounds of the study site. Concentrations of extractable organic material (EOM) ranged from 0.24 to 119.26‰ in the sediment samples, while methane concentrations in the water samples were from 0.037 to 66.474 μM. The visible biological community was predominantly composed of the chemosynthetic tube worms (Vestimentifera) Lamellibrachia sp. and Escarpia sp., and an undescribed, methane-oxidizing mussel (Mytilidae: Bathymodiolus-like), as well as diverse non-chemosynthetic organisms. The ranked abundance of tube worms was significantly correlated (p<0.05) with the concentration of EOM in the sediment samples, while the abundance of mussels was significantly correlated (p<0.05) with the concentration of methane in the water samples. Tube worms and mussels both occurred in dense clusters; however, the clusters of mussels had a more restricted distribution within the study site than did clusters of tube worms. Both organisms were most abundant in the vicinity of the subsurface fault.

Control of volatile organic compounds by an AC energized ferroelectric pellet reactor and a pulsed corona reactor

Abstract: Two laboratory-scale plasma reactors, an alternating-current-energized ferroelectric (high-dielectric ceramic) packed-bed reactor and a nanosecond pulsed corona reactor, were constructured. The aim was to develop baseline engineering data to demonstrate the feasibility of applying plasma reactors to the destruction of various volatile organic compounds (VOCs). Gas retention time, concentration, and corona power were varied to determine the effect on destruction efficiency, using gas chromatography for each VOC. Complete destruction was obtained for toluene. Conversions of methylene chloride at 95% and trichlorotrifluoroethane (known as CFC-113) at 67% were achieved. The conversion was dependent on the electron energy of the reactor and was also related to how strongly the halogen species were bonded with carbon. >

Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking.

Abstract: The disposition of radiolabeled cocaine in humans has been studied after three routes of administration: iv injection, nasal insufflation (ni, snorting), and smoke inhalation (si). Metabolism, followed by urinary excretion of metabolites, proved to be the major route of elimination in all cases. Hydrolytic products (benzoylecgonine, ecgonine methyl ester) were the major excretion products. Benzoyl ecgonine was generally most prevalent, but after smoking two subjects excreted larger amounts of ecgonine methyl ester and the ratio of the two compounds averaged lower in subjects who smoked cocaine. Low binding of cocaine to plasma proteins was observed and blood to plasma ratios were essentially unity. The volume of distribution of cocaine is low (2.70 liter/kg for V beta). Absorption of smoked cocaine was rapid (half-time of 1.1 min). Absorption after ni was slower (half-time of 11.7 min). After iv injection, a rapid distribution phase was observed (half-life of 11 min) and the elimination half-life was 78 min. In 16 subjects divided into three groups based on routes, the half-life based on the average rate constant was 69 min. Bioavailability was good after ni (80%). Undecomposed cocaine from si was well absorbed, but observed bioavailability was diminished by degradation from heating.

Regeneration of fertile plants from protoplasts of elite inbred maize

Abstract: We have obtained friable, non-mucilaginous embryogenic callus from cultured immature embryos of an elite maize inbred line derived from Iowa stiff stalk synthetic germplasm. This callus was used to generate embryogenic cell suspensions containing compact clumps of densely cytoplasmic cells. Plants were readily regenerated from the suspensions, which were also an excellent source of protoplasts. The suspension cultures maintained their plant regeneration capacity through many months. The cultures were cryopreserved in liquid nitrogen and embryogenic callus and suspension cultures were routinely recovered from cryopreserved cells. Protoplasts were isolated in large numbers from both primary and cryopreserved suspension cultures. Cultured protoplasts divided and formed embryogenic callus both when plated in agarose and on nurse cultures. Hundreds of plants were regenerated from protoplast-derived calli. Plants with viable progeny were obtained although many of the regenerates showed morphological and reproductive abnormalities.

Remote plasma enhanced CVD method and apparatus for growing an epitaxial semiconductor layer

Abstract: A remote plasma enhanced CVD apparatus and method for growing semiconductor layers on a substrate, wherein an intermediate feed gas, which does not itself contain constituent elements to be deposited, is first activated in an activation region to produce plural reactive species of the feed gas. These reactive species are then spatially filtered to remove selected of the reactive species, leaving only other, typically metastable, species which are then mixed with a carrier gas including constituent elements to be deposited on the substrate. During this mixing, the selected spatially filtered reactive species of the feed gas chemically interacts, i.e., partially dissociates and activates, in the gas phase, the carrier gas, with the process variables being selected so that there is no back-diffusion of gases or reactive species into the feed gas activation region. The dissociated and activated carrier gas along with the surviving reactive species of the feed gas then flows to the substrate. At the substrate, the surviving reactive species of the feed gas further dissociate the carrier gas and order the activated carrier gas species on the substrate whereby the desired epitaxial semiconductor layer is grown on the substrate.

A new method that simultaneously aligns and reconstructs ancestral sequences for any number of homologous sequences, when the phylogeny is given.

Abstract: Among the fundamental problems in molecular evolution and in the analysis of homologous sequences are alignment, phylogeny reconstruction, and the reconstruction of ancestral sequences. This paper presents a fast, combined solution to these problems. The new algorithm gives an approximation to the minimal history in terms of a distance function on sequences. The distance function on sequences is a minimal weighted path length constructed from substitutions and insertionsdeletions of segments of any length. Substitutions are weighted with an arbitrary metric on the set of nucleotides or amino acids, and indels are weighted with a gap penalty function of the form gk = a + (bXk), where k is the length of the indel and a and b are two positive numbers. A novel feature is the introduction of the concept of sequence graphs and a generalization of the traditional dynamic sequence comparison algorithm to the comparison of sequence graphs. Sequence graphs ease several computational problems. They are used to represent large sets of sequences that can then be compared simultaneously. Furthermore, they allow the handling of multiple, equally good, alignments, where previous methods were forced to make arbitrary choices. A program written in C implemented this method; it was tested first on 22 5s RNA sequences.

2,4-Diamino-5-benzylpyrimidines and analogs as antibacterial agents. 12. 1,2-Dihydroquinolylmethyl analogs with high activity and specificity for bacterial dihydrofolate reductase

Abstract: Twelve 2,4-diamino-5-[(1,2-dihydro-6-quinolyl)methyl]pyrimidines containing gem-dimethyl or fluoromethyl substituents at the 2-position of the dihydroquinoline ring were prepared by condensations of dihydroquinolines with 2,4-diamino-5-(hydroxymethyl)pyrimidine. The dihydroquinolines were produced from the reaction of anilines with mesityl oxide or fluoroacetone. In some cases, 1-aryl-2,4-dimethylpyrroles were obtained as byproducts. Most of these pyrimidines were highly inhibitory to Escherichia coli dihydrofolate reductase (DHFR) and also had high specificity for the bacterial enzyme. 2,4-Diamino-5-[[1,2-dihydro-2,4-dimethyl-3-fluoro-2-(fluoromethyl)-8- methoxy-6(1H)quinolyl]methyl]pyrimidine had an apparent Ki value for E. coli DHFR 13 times lower than that of the control, trimethoprim (1), and was 1 order of magnitude more selective for the bacterial enzyme. It had outstanding activity against Gram-positive organisms in vitro, as well as broad-spectrum antibacterial activity equivalent to that of 1. The results of in vivo testing will be reported elsewhere. The gem-dimethyl substituents of the dihydroquinoline derivatives are considered to be responsible for the high selectivity, as well as contributing to potent bacterial DHFR inhibition. Molecular models are presented which suggest the probable interactions with the bacterial enzyme.

p Value Adjustments for Multiple Tests in Multivariate Binomial Models

Abstract: Data from rodent carcinogenicity (preclinical) and clinical studies involving new drugs may be modeled as having come from multivariate binomial distributions. In two-year rodent carcinogenicity studies, there are typically 20–50 tissues examined for occurrence of any of several possible lesions. For a particular treatment group, the number of occurrences of a particular lesion at a particular tissue may be modeled as binomial, and the vector of such frequencies may be considered multivariate binomial with unspecified dependence structure. The same model may also apply to clinical side-effects data; in this case the marginal frequencies may represent occurrences of events ranging from headaches to ingrown toenails. Frequently, the goal of such studies is to isolate site-specific significant differences between treatment and control groups. For example, in rodent carcinogenicity analyses it is generally not sufficient to claim that a new compound causes an increase in tumors at some unspecified si...

Tumor-elicited polymorphonuclear cells, in contrast to "normal" circulating polymorphonuclear cells, stimulate invasive and metastatic potentials of rat mammary adenocarcinoma cells.

Abstract: Circulating polymorphonuclear cell (PMN) levels rise in proportion to the metastatic potential of the tumor in 13762NF mammary adenocarcinoma tumor-bearing rats. These tumor-elicited PMNs (tcPMNs) secrete high levels of the basement-membrane-degrading enzymes, type IV collagenase and heparanase, suggesting that metastatic tumor cells stimulate neutrophilia so that the tcPMNs might assist tumor cell extravasation during metastasis. To test this hypothesis, purified proteose peptone-elicited PMNs from peritoneal exudate, circulating normal PMNs, and tcPMNs were evaluated for their effects on in vitro invasive and in vivo metastatic potentials of syngeneic 13762NF mammary adenocarcinoma tumor cells. tcPMNs caused a dose-dependent increase in invasion through a reconstituted basement membrane barrier in an in vitro invasion assay. At PMN:tumor cell ratios of 30:1, invasion potential significantly (P less than 0.05) rose to 26-fold, 40-fold, and 37-fold for poorly metastatic MTLn2 cells, highly metastatic MTLn3 cells, and moderately metastatic MTF7 cells, respectively. In contrast, purified proteose peptone-elicited PMNs and circulating normal PMNs did not significantly alter invasive potential. Intravenous coinjections of purified proteose peptone-elicited PMNs did not change the number of experimental lung metastases, but tcPMNs at ratios to 50:1 significantly raised the mean number of metastases 23-fold for MTLn2, 3- to 4-fold for MTLn3, and 1.6- to 1.8-fold for MTF7. These results demonstrate that tcPMNs contribute to the metastatic propensity of mammary adenocarcinoma clones by increasing efficiency of invasion through basement membrane.

Multiple power-density windows and their possible origin.

Abstract: We have previously reported that in vitro exposure of chick forebrain tissue to 50-MHz radiofrequency (RF) electromagnetic radiation, amplitude modulated (AM) at 16 Hz, would enhance the efflux of calcium ions within only two power-density ranges: one from 1.44 to 1.67 mW/cm2, and the other including 3.64 mW/cm2. No effect on efflux occurred at 0.37, 0.72, 2.17, and 4.32 mW/cm2. We confirmed and extended these results by testing at another set of power densities, which included the range of the previous study. Forebrain tissue from 1-7-day-old chickens was labeled in vitro with radioactive calcium ions (30 min, at 37 degrees C), rinsed, placed in a physiological salt solution, and then exposed for 20 min to 50-MHz radiation, AM at 16 Hz, in a transverse electric and magnetic field (TEM) cell maintained at 37 degrees C. The solution was then assayed for radioactive calcium activity. A power-density series was tested. An enhanced efflux of calcium ions was found at 1.75, 3.85, 5.57, 6.82, 7.65, 7.77, and 8.82 mW/cm2; no change was observed at 0.75, 2.30, 4.50, 5.85, 7.08, 8.19, 8.66, 10.6, and 14.7 mW/cm2. Power density is converted to specific absorption rate (SAR) by 0.36 mW/kg per mW/cm2. Even the highest SAR tested (0.005 W/kg) is much too low to result in generalized heating of the sample and thus to be the underlying cause of the enhanced response. A hypothetical mechanism is proposed involving dynamic systems that may account for the power-density dependency as well as for part of the frequency dependency observed with both modulated RF radiation and extremely-low-frequency (ELF) fields.

The purine path to chemotherapy

Abstract: Antimetabolites of purine metabolism have found a use as anti-leukaemic, antiprotozoal and antiviral drugs, in immunosuppression and transplantation, and in gout and hyperuricemia Their mechanisms of action are reviewed

Empirical Bayes Procedures for Stabilizing Maps of U.S. Cancer Mortality Rates

Abstract: The geographic mapping of age-standardized, cause-specific death rates is a powerful tool for identifying possible etiologic factors, because the spatial distribution of mortality risks can be examined for correlations with the spatial distribution of disease-specific risk factors. This article presents a two-stage empirical Bayes procedure for calculating age-standardized cancer death rates, for use in mapping, which are adjusted for the stochasticity of rates in small area populations. Using the adjusted rates helps isolate and identify spatial patterns in the rates. The model is applied to sex-specific data on U.S. county cancer mortality in the white population for 15 cancer sites for three decades: 1950–1959, 1960–1969, and 1970–1979. Selected results are presented as maps of county death rates for white males.

Nobel lecture in physiology or medicine--1988. The purine path to chemotherapy.

Abstract: Research on antimetabolites of nucleic acid purines led to drugs for the treatment of acute leukemia (6-mercaptopurine and thioguanine), gout and hyperuricemia (allopurinol), and herpesvirus infections (acyclovir), and for the prevention of organ transplant rejection (azathioprine).

Screening Approaches to Neurotoxicity: A Functional Observational Battery:

Abstract: Observational tests to assess the behavioral and neurologic integrity of laboratory rats have been advanced for use in the primary screening of chemicals to detect neurotoxic potential. To examine the use of such an approach, we are systematically using a functional observational battery (FOB) to characterize known neurotoxicants and to assess its selectivity, reliability, specificity, and sensitivity. Our FOB is a series of tests that includes home cage and open field observations, neuromuscular and sensorimotor tests, and physiologic measures. Described in this article are the compounds we have tested to date and how the data have been integrated to produce a profile of effects for each. We have found the FOB to be sensitive to a variety of neurotoxicants, whose effects can be distinguished using a type of profile analysis as illustrated herein. This research effort provides important information about both the execution and the interpretation of FOB studies.