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As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.

To develop an automated, accurate and scalable method by which acronym-definition pairs can be identified within text. Its primary advantage is in enabling information processing methods to resolve author-defined acronyms, but it also allows an automated creation of a reference work on acronym definitions. This has several advantages over manual or semi-automated methods, besides time and effort saved, such as enabling identification of relative frequencies for alternate acronyms and definitions as well as spelling, phrasing and hyphenation variants for a unique acronym-definition pair. It also aids users in identifying acronym/definition variants present in the literature that may not necessarily be in biomedical databases.A set of heuristics to accurately locate and identify the boundaries of acronym-definition pairs was developed and refined in terms of precision and recall on subsets of MEDLINE records. These training sets were gradually increased in size and heuristics re-evaluated to ensure scalability.Our final set of Acronym Resolving General Heuristics (ARGH) had a sample-based estimated rate of 96.5 +/- 0.4% precision and 93.0 +/- 2.7% recall when tested on over 12 million MEDLINE records, identifying more than 174,000 unique acronyms and their 737,000 associated definitions.We estimate that as much as 36% of the acronyms in MEDLINE are associated with more than one definition and, conversely, up to 10% of definitions are associated with more than one acronym. The number of unique acronyms in MEDLINE is increasing at a rate of approximately 11,000 per year, while the number of definitions associated with them is growing at approximately four times that rate. Access to the ARGH database is available online at http://lethargy.swmed.edu/ARGH/argh.asp. The heuristic module and database are available upon request.

The usefulness of the light microscope has been dramatically enhanced by recent developments in hardware and software. However, current technologies lack the ability to capture and analyze a high-resolution image representing a broad diversity of spectral signatures in a single-pass view. We show that hyperspectral imaging offers such a technology. METHODS AND RESULTS We developed a prototype hyperspectral imaging microscope capable of collecting the complete emission spectrum from a microscope slide. A standard epifluorescence microscope was optically coupled to an imaging spectrograph, with output recorded by a CCD camera. Software was developed for image acquisition and computer display of resultant X--Y images with spectral information. Individual images were captured representing Y-wavelength planes, with the stage successively moved in the X direction, allowing an image cube to be constructed from the compilation of generated scan files. This prototype instrument was tested with samples relevant to cytogenetic, histologic, cell fusion, microarray scanning, and materials science applications.Hyperspectral imaging microscopy permits the capture and identification of different spectral signatures present in an optical field during a single-pass evaluation, including molecules with overlapping but distinct emission spectra. This instrument can reduce dependence on custom optical filters and, in future imaging applications, should facilitate the use of new fluorophores or the simultaneous use of similar fluorophores.

Allele loss involving chromosome arm 3p is one of the most frequent and earliest known genetic events in lung cancer pathogenesis and may affect several potential tumor suppressor gene regions. To further study the role of chromosome 3p allele loss in the pathogenesis of lung cancer, we performed high resolution loss of heterozygosity (LOH) studies on 97 lung cancer and 54 preneoplastic/preinvasive microdissected respiratory epithelial samples using a panel of 28 3p markers. Allelic losses of 3p were detected in 96% of the lung cancers and in 78% of the preneoplastic/preinvasive lesions. The allele losses were often multiple and discontinuous, with areas of LOH interspersed with areas of retention of heterozygosity. Most small cell lung carcinomas (91%) and squamous cell carcinomas (95%) demonstrated larger 3p segments of allele loss, whereas most (71%) of the adenocarcinomas and preneoplastic/preinvasive lesions had smaller chromosome areas of 3p allele loss. There was a progressive increase in the frequency and size of 3p allele loss regions with increasing severity of histopathological preneoplastic/preinvasive changes. In analyses of the specific parental allele lost comparing 42 preneoplastic/preinvasive foci with those lost in the lung cancer in the same patient (n = 10), the same parental allele was lost in 88% of 244 comparisons for 28 3p markers (P = 1.2 x 10(-36) for this occurring by chance). This indicates the occurrence of allele-specific loss in these foci similar to that seen in the tumor by a currently unknown mechanism. Analysis of all of the data indicated multiple regions of localized 3p allele loss including telomere-D3S1597, D3S1111-D3S2432, D3S2432-D3S1537, D3S1537, D3S1537-D3S1612, D3S4604/Luca19.1-D3S4622/Luca4.1, D3S4624/Luca2.1, D3S4624/Luca2.1-D3S1582, D3S1766, D3S1234-D3S1300 (FHIT/FRA3B region centered on D3S1300), D3S1284-D3S1577 (U2020/DUTT1 region centered on D3S1274), and D3S1511-centromere. A panel of six markers in the 600-kb 3p21.3 deletion region showed loss in 77% of the lung cancers, 70% of normal or preneoplastic/preinvasive lesions associated with lung cancer, and 49% of 47 normal, mildly abnormal, or preneoplastic/preinvasive lesions found in smokers without lung cancer; however, loss was seen in 0% of 18 epithelial samples from seven never smokers. The 600-kb 3p21.3 region and the 3p14.2 (FHIT/FRA3B) and 3p12 (U2020/DUTT1) regions were common, independent sites of breakpoints (retention of heterozygosity by some markers and LOH by other markers in the immediate region). We conclude that 3p allele loss is nearly universal in lung cancer pathogenesis; involves multiple, discrete, 3p LOH sites that often show a "discontinuous LOH" pattern in individual tumors; occurs in preneoplastic/preinvasive lesions in smokers with and without lung cancer (multiple lesions often lose the same parental allele); frequently involves breakpoints in at least three very small defined genomic regions; and appears to have allele loss and breakpoints first occurring in the 600-kb 3p21.3 region. These findings are consistent with previously reported LOH studies in a variety of tumors showing allele loss occurring by mitotic recombination and induced by oxidative damage.

The complex permittivity of various ceramics has been measured at elevated temperatures. The permittivity measurements were made using the cavity perturbation technique at a fixed frequency of 10.1 GHz. The temperature of the sample was varied from 800 to 1000 °C by independently heating the samples using a CO2 laser (up to 27 W) directed into the cavity. The samples were mounted in quartz micropipettes and illuminated through the quartz. The sample temperature was measured using an optical pyrometer. This method is valuable for measuring the microwave properties of solids that normally are exposed to microwave radiation at elevated temperatures such as high‐power microwave sources, components, and windows.

An adaptor for holding a micropipette in a spectrofluorimeter includes a base member for holding the micropipette and an optical system for linearly focusing visible or ultraviolet light onto a sample solution held in the micropipette. Specifically, the optical system includes a cylindrical lens which focuses collimated light from a light source into a line along the axis of the micropipette. The optical system also includes a cylindrical quartz lens which recollimates the light that emerges from the micropipette sample holder in a direction which is perpendicular to the direction of the incident light. A spectrometer is provided to receive the recollimated light for measuring the light absorption and light emission characteristics of the sample material held in the micropipette.

In the present experiments, we characterized the agonist and antagonist effects of butorphanol in mice. In the mouse radiant-heat tail-flick test, the mu agonists morphine and fentanyl and the kappa agonist U50,488H were fully effective as analgesics, whereas butorphanol was partially effective (producing 82% of maximal possible analgesic effect). Naltrexone was approximately equipotent in antagonizing the effects of morphine, fentanyl and butorphanol; in vivo apparent pA2 values for these naltrexone/agonist interactions were 7.5 (unconstrained). Naltrexone was approximately 10 times less potent in antagonizing the effect of U50,488H (average apparent pK(B) = 6.7). The selective mu antagonist beta-funaltrexamine (0.1-1.0 mg/kg) antagonized the effects of butorphanol in a dose-dependent insurmountable manner. Pretreatment with nor-binaltorphimine (32 mg/kg), a kappa-selective antagonist, did not reliably antagonize butorphanol, and naltrindole (20 and 32 mg/kg), a delta-selective antagonist, failed to antagonize the effects of butorphanol. Low doses of butorphanol (1.0, 1.8 or 3.2 mg/kg) caused parallel, rightward shifts in the dose-effect curve for morphine and parallel leftward shifts in the dose-effect curve for U50,488H. Taken together, the results of the present study suggest that butorphanol is a partial agonist in the mouse radiant-heat tail-flick test and that activity at mu receptors accounts for the majority of its antinociceptive effects.

The number of PCR samples that can be simultaneously processed has been dramatically increased over existing practices by using a new polycarbonate 864-well microwell plate and a modified air cycling oven. In thirty 9-min cycles, four plates containing 3455 samples can be amplified in 4.5 h. Amplification is rapid, uniform and reliable from sample to sample and run to run. This PCR method can satisfy the Human Genome Project's need for high-throughput sample analysis using PCR.

A method of plasma production by ion cyclotron wave heating has been developed in RFC-XX. Nagoya Type-III antennas were used for wave excitation, and gas was supplied through a gas box. The effect of the rotating field excitation on plasma production and heating was investigated. In the m = − 1 rotational mode (rotation in the direction of ion cyclotron motion), the plasma density profile is flat within the gas box bore with a line integrated density nl = 3 × 1013cm−2, and the ion temperature is Ti ≈ 150 eV. For the m = +1 mode, a high density plasma was obtained with a different profile having a peak at the centre. In this mode, the line integrated density is nl = 3 × 1014cm−2, with the peak density n(0) = 7 × 1013cm−3.

The loss flux to an azimuthally segmented limiter in the central cell of the cusp end cell stabilized, axisymmetric mirror machine, RFC-XX, shows that non-axisymmetric illumination by either ICH or ECH can induce azimuthal non-uniformities in the plasma. Measurements of the floating potential in the vicinity of the limiter and by the limiter itself suggest that a large stationary azimuthal electric field is induced which can convectively transport plasma across magnetic field lines. The local radial component of the electric drift velocity is as large as 7 × 104 cms−1. Examinatio n of the plasma end loss versus azimuth and probe measurements deep in the plasma show that the non-uniformities extend into the plasma and are not localized near the outer boundary. The data suggest that the RF fields are driving an anomalous radial loss.

1. Fertilized Arbacia eggs contain a readily extracted substance (or substances) which, inour tests, accelerated the rate of cleavage of such eggs to a statistically significant degree.2. The acceleration produced by such an extract is not a result of the echinochrome it may contain nor of possible copper contamination.3. The results are discussed against a background of population physiology, and the problems of over- and undercrowding of organisms.

ALTHOUGH HIGH YIELDS of a desired fermentation product can often be obtained by empirical manipulations of the environment in which a given organism is expected to be productive, it is more satisfying scientifically to base such control, if possible, on a closer acquaintance with the nature of the fermentation. For instance, high yields of penicillin are accompanied by characteristic metabolic changes in the medium; both can be attained by changing the physical or chemical milieu of the organism (cf. Jarvis and Johnson, 1947). Early experiments with Streptomyces griseus seemed to support the hypothesis that streptomycin production would follow a similar pattern (Garner et al., 1950); however, subsequent results showed that the relation between high streptomycin yields and gross metabolism, at least as embraced by our studies, was obscure more often than not. Waksman et al. (1946) first reported some of the changes occurring, during growth of a streptomycinproducing organism. They found a gradual rise in pH of the culture on a glucose, peptone, meat extract medium, and an increase in ammonia and amino nitrogen; accumulation of streptomycin paralleled the growth of the organism. Gottlieb and Anderson (1947) used a vegetative inoculum, which gives more rapid growth, and found that the peak of streptomycin production lagged behind the growth peak. Synthesis of streptomycin proceeded only in the presence of oxygen, and there was no correlation between pH changes and streptomycin production. Dulaney and Perlman (1947) compared the chemical changes that occurred during the submerged growth of organisms in Waksman's medium and media that contained high levels of either phosphate or carbohydrate. The growth phase was accompanied by reduction of soluble medium constituents, a high oxygen demand, and little streptomycin production. This was followed by an autolytic phase in which inorganic phosphorus and soluble nitrogen were released, the oxygen demand dropped, and streptomycin was produced. Added phosphate reduced streptomvcin yields, while high levels of carbohydrate had little effect aside from prolonging the growth phase. We have isolated a culture capable of giving relatively high yields and have attempted to analyze

1. We confirm the observation of Bürk (1965) that Neurospora crassa NADP-linked glutamate dehydrogenase normally exists in an inactive form below pH7.0 and in a fully active form above pH8.0 in either tris or orthophosphate buffer. At pH7.4 the enzyme is about half activated at 25 degrees . 2. The variety of the enzyme produced by the mutant am(2l) shows a similar behaviour except that the transition is shifted about one pH unit in the alkaline direction. 3. The am(2l) enzyme has previously been reported to be activated by brief warming to 30 degrees in phosphate buffer at pH8.0. The wild-type enzyme shows a similar effect at pH7.0. In tris buffer this effect is much less pronounced. 4. The am(2l) enzyme is extremely unstable at 47 degrees at pH7.0; its stability is somewhat greater at lower pH, and is markedly increased by increasing the pH in the range 7.0-8.7. The wild-type enzyme also shows an indication of a stability minimum at pH7.0, but a temperature of 60 degrees is needed for a measurable rate of inactivation. 5. The inactive form of the enzyme is much more subject to thermal irreversible denaturation than is the active form.

The diffusion coefficient D⊥ for a collisionless hydrogen plasma was measured in the levitated octupole when a weak toroidal field was added. A twenty‐fold decrease in the anomalous diffusion was observed with Bt/Bp≳0.1. This reduced level of diffusion was still two orders of magnitude larger than the classical value and the residual level of convective cell activity was responsible for the enhanced transport. Locally trapped particles in the poloidal field mirrors allow the convective cell activity (f