cssi/SciSciGPT-SciSciNet huggingface dataset:
Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

Background: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Method: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Results: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint. Conclusions: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.
Plasma source mass spectrometry

Abstract Over the past decade, plasma-source mass spectrometry (PSMS) has become a viable alternative for multielemental analysis. The method offers (1) detection limits that are ordinarily two orders of magnitude below those offered by competitive emission techniques, (2) effective semiquantitative analysis, (3) isotope-analysis and isotope-ratio capability, (4) a broad linear dynamic range, and (5) virtually complete elemental coverage. However, even the most modern PSMS instruments remain plagued by a number of problems. High concentrations of sample material often pose difficulties, a number of spectral interferences (isobaric overlaps) can be devastating, instrumental drift is often troublesome, and new kinds of matrix interferences, not yet satisfactorily explained, are frequently encountered. In this paper, the current status of PSMS is first briefly reviewed, with an emphasis on current capabilities and shortcomings. A sampling of recent activities in the field is then documented. These activities understandably are aimed mostly at overcoming the remaining shortcomings of the method. Finally, recent instrumental developments are outlined. Included in these developments are modifications of conventional plasma ion sources, the introduction of new plasmas for PSMS, and the use of alternative mass spectrometers for elemental analysis.
STUDIES ON THE INNERVATION OF THE STAPEDIUS MUSCLE OF THE CAT.

A study of nerve-muscle relations and fine innervation patterns is reported for the stapedius muscle of the cat. Gross relations of the muscle to its associated nerves and other middle ear structures are shown by illustrations. Histologic features of innervation are studied with the Bodian silver method. the thiocholine technique, and iron hematoxylin and osmic acid stains. The muscle is richly supplied by 3 to 4 facial nerve branches in which no axons are found above 8 μ and the majority are unimodally grouped at 2–4 μ. The auricular nerve of the vagus does not penetrate the muscle. Three to four distinct zone is of fasciculi are found whose muscle fibers are 14–20 μ in diameter. Each zone is supplied by primary nerves whose branches do not exhibit terminal overlap or multiple innervation of muscle fibers. Short terminal axons lead to motor and plates from all intramuscular nerve branches. Nerve branches and motor end plates are confined to the basal third of the muscle. Sensory endings are not detected within the muscle or its tendon. It is estimated that each motor neuron supplies no more than five muscle fibers but more probably three or less.
Some statistical problems in connection with word association data

Abstract Four word association tables recently fitted to the Yule distribution by W. J. Horvath are analyzed more fully by (a) comparing them with two other theoretical alternatives, (b) illustrating various methods for parameter estimation, (c) illustrating the usefulness of the Smirnov goodness-of-fit test, and (d) using a conjecture of Zipf to derive a stochastic model leading to the zeta distribution.
‘‘Heisenberg microscope’’ decoherence atom interferometry

Atom de Broglie--wave interference fringes are revealed by their selective destruction. A thermal potassium beam is transmitted through a Talbot-Lau atom interferometer. Different fringe Fourier components resonate in the interferometer at different atomic velocities. The thermal velocity distribution averages and washes out the high-frequency components. ac-modulated laser light passes through the interferometer, is scattered by atoms at one velocity, and destroys, and thereby reveals via the ac modulation, the associated high-frequency fringe contribution.
Nanogap multi-electrode atom and conductivity prober

We report on a nano-prober system that can image atoms, and also measure the surface electrical conductivity with multiple probes with <;100nm spacing, a capability that allows mapping of electrical conductivity of atomically thin films. Investigating nanoscale properties of atomically thin two-dimensional films such as graphene require precision control of sensing electrodes over atomic dimensions. Atomic probing is conducted using microfabricated probes in Scanning Tunneling Microscopy (STM) or Atomic Force Microscopy (AFM) mode, where the probes are navigated using PZT actuators and carrying out mechanical or electrical measurements, leading to a bulky actuator. AFM and STM allow conductivity measurements through the tip and the film, they do not allow measurement of conductivity on the film surface. The size of the tip handling actuation prevents two tips to be placed within a few tens of nanometer apart for nanoscale conductivity measurement. In this paper, we demonstrate nano-tip arrays for probing with integrated electrostatic actuators for measurement of surface conductivity. We have used our system to measure surface conductivity of HOPG substrate, measuring a conductivity of 0.4 Ω/nm2, with a tip gap of 300 nm.
The use of a microcrystalline wax in tablet polishing. I

Microcrystalline waxes have a multiplicity of uses. The production of a polish is very desirable on coated tablets. Two microcrystalline waxes from petroleum are produced by the Bareco Oil Company of Barnsdall, Okla. One melts at 170° F. and the other at 190° F. This paper deals with the wax of lower melting point and evidence is presented to show that when it is mixed with carnauba (or possibly some similar product) a satisfactory polish is produced.
On welfare measurement in cities

This paper extends project evaluation in a spatial urban economy to consider the more general case of distortionary public finances. If a local public improvement is financed at least in part by a distortionary property tax, we show that residential land prices do not accurately measure the value of land improvements—even when households are identical and the improvement is infinitesimally small. The magnitude and direction of the measurement error will depend on the second-order effects on aggregate demand via changes in population density at each location and on overall city size.
Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells

The transcription factor Foxp3 is indispensable for the ability of regulatory T cells (Treg cells) to suppress fatal inflammation. Here we characterized the role of Foxp3 in chromatin remodeling and the regulation of gene expression in actively suppressive Treg cells in an inflammatory setting. Although genome-wide occupancy of regulatory elements in DNA by Foxp3 was similar in resting Treg cells and those activated in vivo, Foxp3-bound enhancer elements in the DNA were poised for repression only in activated Treg cells. Following activation, Foxp3-bound sites showed diminished accessibility of chromatin and selective deposition of histone H3 trimethylated at Lys27 (H3K27me3), which was associated with recruitment of the histone methyltransferase Ezh2 and downregulation of the expression of nearby genes. Thus, Foxp3 poises its targets for repression by facilitating the formation of repressive chromatin in Treg cells upon their activation in response to inflammatory cues.
Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion

Oranges are rich sources of flavonoids that are bioactive and may protect against age-related diseases. The absorption of orange flavanones may be affected by factors such as processing and subject anthropometric variables, and the bioactivity of the absorbed phytochemicals depends on how they are metabolised during absorption. In a randomised cross-over study, twenty subjects consumed a single portion of orange fruit (150 g) or juice (300 g) that contained the flavanones narirutin and hesperidin, and an additional 109 subjects across a broad age range (18-80 years) consumed the juice. Flavanone metabolites were measured in regularly collected samples of plasma and urine. After consumption of fruit or juice, flavanone conjugates, but not the aglycones, were detected in plasma and urine. The flavanone conjugates were shown to include the 7- and 4'-O-monoglucuronides of naringenin, the 7- and 3'-O-monoglucuronides of hesperetin, two hesperetin diglucuronides and a hesperetin sulfo-glucuronide, but no aglycones or rutinosides. Analysis of the plasma pharmacokinetic and urinary excretion data on a dose-adjusted basis indicated no difference in absorption or excretion of either flavanone between the fruit and juice matrices. In the extended urinary excretion dataset the individual variation was very large (range 0-59 % urinary yield). There was a small but significant (P < 0.05) decrease in the excretion of hesperetin (but not naringenin) with increasing age (P < 0.05), but the effects of sex, BMI and contraceptive pill use were shown not to be associated with the variation in flavanone excretion.
Seed germination traits of annuals and emergents recruited during drawdowns in the Delta Marsh, Manitoba, Canada

Seed germination traits of the most abundant mudflat annuals and perennial emergents that become established during drawdowns (periods when all or part of a wetland is free of standing water) in the Delta Marsh, Manitoba, Canada, were examined. Seeds of both annuals (Aster laurentianus Fern., Atriplex patula L. and Chenopodium rubrum L.) and emergent perennials (Hordeum jubatum L., Scolochloa festucacea (Wild.) Link, Phragmites australis (Cav.) Trin. ex Steud. and Typha glauca Godr.) from this prairie, lacustrine marsh germinated best in the light. Stratification also improved the seed germination percentages of all species except for Scolochloa. Germination percentages were highest in alternating 15/25°C and 20/30°C temperature regimes and lowest in a 5/15°C regime, Seed germination percentages for all species were highest when the seeds were on the surface and declined sharply when seeds were covered by as little as 1 cm of sand. Seedlings of species with large seeds (e.g. Hordeum and Scolochloa) could reach the surface from soil depths of down to 5 cm wheras seedlings of the smallest seeded species (Typha) could reach the surface from no more than 1 cm depth. Seed germination of Hordeum and Phragmites was unaffected by salinities as high as 5000 mg l−1 of NaCl, whereas seed germination of Typha and Scolochloa was reduced significantly by 1000 mg l−1 of NaCl. Of the three annuals, seed germination of Aster was least affected by increasing salinity levels (no effect until 4000 mg l−1) while that of Chenopodium was the most sensitive (reduced at 2000 mg l−1). Because the germination of seeds of each species is affected differently by temperature, salinity, light conditions and depth of burial, microenvironmental variations from site to site during a drawdown could result in different species becoming established at sites with identical seed banks.
Reevaluation of the role of atrial systole to cardiac hemodynamics: Evidence for pulmonary venous regurgitation during abnormal atrioventricular sequencing

Abstract Twenty open-chest dogs with experimental AV heart block were evaluated hemodynamically, angiographically, and by M-mode echocardiography to further elucidate mechanisms whereby abnormal AV sequencing results in decreased cardiac hemodynamics. During fixed-rate AV pacing, there was a consistent decrease in cardiac output, left ventricular and aortic pressures, and left ventricular dimensions with an increase in left atrial pressure as the AV interval was decreased from 100 to 0 msec, and there were further changes when the AV interval was set at −50 and −100 msec. The hemodynamic consequences of atrial fibrillation with regular ventricular rhythms were similar to the effects of an AV interval of 0 msec. It is important to note that retrograde blood flow into the pulmonary venous system (pulmonary venous regurgitation) was demonstrated by left atrial angiography at AV intervals of both −50 and −100 msec. However, left ventricular angiography failed to reveal mitral regurgitation during fixed-rate pacing at any AV interval or during atrial fibrillation with regular ventricular rates. Thus, during tachyarrhythmias characterized by abnormal AV sequencing, not only is there the loss of active atrial contribution to ventricular filling but there is also evidence for a retrograde or “negative atrial kick” further compromising cardiac hemodynamics.
Quality evaluation of four sources of brine shrimp Artemia spp.

A study was conducted to compare fatty acid composition, hatching quality, and size of nauplii from four commercial sources of brine shrimp (Artemia spp.) cyse: China (CH), Colombia (COL), Great Salt Lake (GSL), and San Francisco Bay (SFB). The CH brine shrimp had a comparatively high percentage of 20:5(n-3) fatty acid (eicosapentaenoic acid or EPA), an essential fatty acid for most Iarval fishes, which was 10.4% of the total lipids. The COL, GSL, and SFB sources of cysts contained comparatively low percentages of EPA, 2.9, 1.2, and 1.6%. respectively. Hatching quality was determined by hatching cysts in salt (NaCl) water with a specific gravity of 1.02 at 27 C for 42 h. The COL cysts had the fastest hatching rate, with 50% of the cysts hatching in 13.4 h, while CH cysts hatched at the slowest rate, requiring 25.6 h for 50% of the cysts to hatch. Total percentage hatch was not significantly different among the SFB, COL, and GSL sources, with an average hatching percentage of 84.5, while CH cysts had a significantly lower total percentage hatch of 67.5. The SFB source produced the greatest number of nauplii (1.6 ± 105 per g of cysts) with the smallest length (382 μm), while CH produced the smallest number (8.7 ± 104) with the greatest length (500 μm). These results indicate that there is great variation in nutritional quality, hatching quality, and size of nauplii among commercial sources of brine shrimp cysts, and each of these criteria should be considered in selecting brine shrimp in a development of a feeding strategy for larval culture of a particular species.
Electro-adaptive microfluidics for active tuning of channel geometry using polymer actuators

With the expanding role of microfluidics in biology and medicine, methodologies for on-chip fluid sample manipulation become increasingly important. While conventional methods of microfluidic actuation, such as pneumatic and piezoelectric valves, are well characterized and commonly used, they require bulky external setups and complex fabrication. To address the need for a simple microfluidic actuator, we introduce a hybrid device consisting of an electroactive polymer that controls the shape of a microfluidic channel with an applied bias voltage. The electro-adaptive microfluidic (EAM) device allowed tuning of fluidic resistances by up to 18.1 %. In addition, we have shown that the EAM device is able to clear microchannel blockages by actively expanding the channel cross section. Biocompatibility tests show the EAM device has little effect on cell viability within a voltage range and thus has the potential to be utilized in bio-microfluidic systems. All of these results indicate that this EAM device design may find use in applications from cell sorting and trapping and self-clearing channels, to the reduction of lab-on-a-chip complexity via tunable channel geometries.
Interpenetrating polymer networks of photocrosslinkable cellulose derivatives

A series of interpenetrating polymer networks has been prepared from two cellulose derivatives, one of which contains cinnamate groups and the other containing randomly substituted cinnamate and allyl groups. The latter derivative forms a crosslinked network in less than 5 min on exposure to ultraviolet radiation and can be used to make amorphous interpenetrating polymer networks containing 50% by weight loading level of crosslinked vinyl polymers. The syntheses of both derivatives and the thermal properties and film morphologies of their interpenetrating polymer networks are discussed. © 1996 John Wiley & Sons, Inc.
Measuring Variability of Performance Among Individual Swine Producers

Quarterly performance data of swine producers were analyzed to determine variability of productivity and economic factors. Means of performance measures for the top, middle, and bottom producer groups were different, but the variances were not. Variability of productivity measures was greater across producers than for most individual producers over time. Producers' relative rankings on performance measures exhibited considerable stability. Of the factors considered, feed efficiency and pigs sold per sow per year had the largest effects on returns to management and labor. Variability in pork production is quite different from crop production, and this has implications for producers, those working with producers, and researchers.
Flow cytometric detection of human immunodeficiency virus type 1 proviral DNA by the polymerase chain reaction incorporating digoxigenin‐ or fluorescein‐labeled dUTP

Serological assays are routinely used in the laboratory diagnosis of human immunodeficiency virus type-1 (HrV-1) infection, but the polymerase chain reaction (PCR) is ultimately the most sensitive and direct method for establishing definitive diagnosis. As an alternative to the conventional radioactive PCR procedure we have developed and evaluated a pair of rapid nonradioisotopic flow cytometric detection methods. Using heminested PCR we directly incorporated fluorescein-12-dUTP (fluo-dUTP) or digoxigenin-11-dUTP (dig-dUTP) into the PCR-amplicons. The labeled amplicons were hybridized with biotinylated antisense and sense probes, followed by capture of the hybrid DNA using streptavidin-coated beads which were finally analyzed in a flow cytometer by (1) direct detection of the fluorescence intensity of the amplicons incorporating fluo-dUTP and (2) immunodetection of the amplicons incorporating dig-dUTP by anti-digoxigenin IgG labeled with fluorescein isothiocyanate (FITC). Although both assays were functionally comparable with radiolabeled probe in reliably detecting as low as five copies of HIV-1 proviral DNA sequences, the immunodetection of dig-dUTP consistently yielded higher mean channel fluorescence and gave a stable signal over an extended period of 12-14 weeks. In testing a panel of 20 pedigreed PBMC specimens from blood donors with or without HIV-1 infection, the results of both flow cytometric assays were identical withmore » those of the conventional radioactive procedure. Therefore, we conclude that the dig-dUTP incorporation in amplicons, hybridization with a pair of sense-antisense biotinylated probes and immunodetection of hybrids by flow cytometric analyses is the nonisotopic method of choice for PCR-diagnosis of HIV-1 infection. 21 refs., 2 figs., 4 tabs.« less
Sex differences in the dietary modulation of pancreatic cancer in Syrian hamsters treated continuously with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine.

The effect of continuous week-long administration of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) by s.c. implanted osmotic pumps was examined in male and female Syrian hamsters given access to three isocaloric synthetic diets containing 10 (LP), 20 (MP) and 30% (HP) casein respectively. At a total dose of 210 mg/kg, toxicity of HPOP, expressed as acute liver injury, was greater in male than in female hamsters. Such toxicity increased with protein intake in male, but not in female animals. Twenty-five weeks after initiation, female and male hamsters developed pancreatic ductal adenocarcinomas and to a lesser degree liver cholangiocellular and hepatocellular carcinomas. The highest incidence of pancreatic cancer was observed under HP diet regimens and was 75 and 67% in female and male hamsters respectively. Decrease of protein intake resulted in the reduction of the incidence of pancreatic cancer, which was more striking in males than in females. In males fed the MP and LP diets respectively, such an incidence declined to 33 and 6%. Although significant differences in the incidence of pancreatic cancer were not observed among female groups fed the above three diets, the multiplicity and the number of such tumors were significantly greater at the HP than the LP level. Differences in the incidence of pancreatic tumors between males and females were statistically significant only at the LP level. However, such differences were also significant at the MP level when comparisons were based on tumor number and multiplicity. Since the incidence, tumor multiplicity and size were generally greater in female than male hamsters, estrogenic hormones may play a role in the development of pancreatic ductal adenocarcinomas in this species.
Evanescent Electric Field Amplitudes in Thin Lipid Films for Internal Reflection Infrared Spectroscopy

Internal reflection infrared spectroscopy is a commonly used technique for determining the conformation and orientation of polypeptides in thin films such as supported lipid membranes. Accurate determinations of molecular orientation by this technique depend on accurate calculations of evanescent electric field amplitudes. These calculations, in turn, depend on film thickness and assumptions about the dielectric behavior within such films. Different assumptions lead to either two-phase or three-phase approximations for calculating electric field amplitudes, and both approximations are widely used. To test the accuracy of these approximations, we have examined a series of trisubstituted benzenes for their suitability as an internal orientation reference standard. We find that 1,3,5-tri-tert-butyl-benzene is absorbed into supported lipid membranes and exhibits an infrared absorption dichroism that is well described by the two-phase approximation but is inconsistent with the three-phase approximation. These ...
Evolution of radio structure in quasars: a new probe of protogalaxies?

Analysis of new high-resolution radio observations of quasars with redshifts >1.5 shows that these powerful extragalactic radio sources have epoch-dependent physical properties. Distant quasars have a more bent, distorted appearance and are smaller than those nearby. The ambient medium, interacting with the radio jets, is postulated as playing an important role in producing these epoch-dependent effects. Optical absorption line studies are important in this respect. These observations provide an important new probe of young galaxies and their formation.
Interdependence of cdk2 Activation and Interleukin-2Rα Accumulation in T Cells *

We have shown previously that serum promotes T cell proliferation by acting with T cell receptor (TCR) agonists to efficiently down-regulate p27Kip1 and activate cdk2-containing complexes. In the studies described here, the effect of serum on the expression of the α subunit of the interleukin-2 receptor (IL-2Rα) was examined. We found that serum was required for maximal and sustained IL-2Rα protein expression and consequent IL-2 signaling in TCR-activated splenocytes. Serum had no effect on IL-2Rα mRNA levels and thus modulates IL-2Rα expression post-transcriptionally. Unlike wild-type splenocytes, splenocytes exhibiting serum-independent cdk2 activation due to loss of p27Kip1 efficiently expressed IL-2Rα in serum-deficient medium. Conversely, serum did not promote IL-2Rα accumulation in conditions in which cdk2 activity was blocked. These findings demonstrate that cdk2 activation is necessary and sufficient for IL-2Rα accumulation in TCR-stimulated splenocytes. On the other hand, IL-2 signaling was required (at least in part) for cdk2 activation in these cells. Thus, cdk2 activation, IL-2Rα expression, and IL-2 signaling are interdependent events, and we suggest that this feed-forward regulatory loop plays a key role in T cell mitogenesis.
Immune‐Based Therapy for HIV Infection: Are Acute and Chronic HIV Infection Different Diseases?

Increased T cell activation is now widely accepted as an important factor in the pathogenesis of HIV. Although the direct infection and killing of CD4+ T cells by HIV contributes to the progressive loss of these cells over time, generalized T cell activation and apoptosis may be the most important mechanisms whereby HIV causes immune deficiency [1, 2]. T cell activation, rather than a high level of viral replication, is the primary feature that distinguishes pathogenic from nonpathogenic simian models of HIV infection [1, 3]. The extent of T cell activation may be a better predictor of subsequent T cell decrease than is the extent of viral replication [4, 5], and persistent T cell activation during antiretroviral therapy (ART) is associated with fewer treatment-mediated increases in CD4' T cell counts [6]. Chronic inflammation may also drive some of the non-HIV-related complications associated with HIV disease, including accelerated atherosclerosis.
Predicting drying in coatings that react and gel : Drying regime maps

The competition between drying and reactions in a liquid coating containing precursors to a random network polymer can give rise to a variety of drying phenomena. Solidification, or gelation, of the polymer may occur before, after, or during the removal of solvents from the coating. Rates of drying and reaction are probed by solving the equations of mass transfer by diffusion along with chemical reaction in one dimension. Solutions to this system of equations are obtained by Galerkin's method with finite-element basis functions and entail large-scale computation. Skinning, or solidification at the surface of the coating while the bulk is still liquid, occurs in thick coatings when the diffusional resistance to drying is significant, that is, at high mass-transfer coefficients. Homogeneous solidification occurs in thin coatings at low mass-transfer coefficients. Drying regime maps represent these solidification phenomena as regions in parameter space.
Diffuse lung disease in infancy: a proposed classification applied to 259 diagnostic biopsies.

Thoracoscopic and open lung biopsies are being performed with increasing frequency in neonates and infants and are an important component of the diagnostic evaluation of respiratory compromise in these very young children. Diffuse lung disease in infancy includes a wide spectrum of developmental, genetic, inflammatory, infectious, and reactive disorders. The majority of the entities diagnosed in infancy (68%) in this retrospective lung biopsy series are seen almost exclusively in this age group and not in older children and adults. These include primary disorders of pulmonary and pulmonary vascular development, secondary disorders affecting prenatal and/ or postnatal lung growth, genetic disorders of surfactant function, pulmonary interstitial glycogenosis, and neuroendocrine cell hyperplasia of infancy. Although the diagnostic approach to infant lung biopsies is guided primarily by the clinical history and imaging findings, all cases require careful assessment of alveolar growth, vascular architecture, i...
Effects of disulfiram on hepatic P450IIE1, other microsomal enzymes, and hepatotoxicity in rats.

Abstract Disulfiram, widely used in avoidance therapy for alcohol abuse, has been shown to have protective effects against chemically induced toxicity and carcinogenesis. The purpose of this work was to elucidate the biochemical mechanisms of this protective action by examining its effects on cytochrome P450IIE1 and other related microsomal enzyme activities. When a dose of disulfiram was given intragastrically to rats, a very rapid decrease of N -nitrosodimethylamine (NDMA) demethylase activity, possibly due to the inactivation of P450IIE1, was seen. The loss of P450IIE1 protein from the microsomal membrane was observed at 18 hr after receiving disulfiram, but not within the first 5 hr after the treatment. P450IIB1, on the other hand, was induced markedly between 15 and 72 hr after the disulfiram treatment. The treatment, however, caused only moderate changes in some other P450 isozymes. Carbon disulfide, a putative metabolite of disulfiram, produced similar effects on P450IIE1, but with shorter duration. Carbon disulfide, however, did not induce P450IIB1. Diethyldithiocarbamate, a reductive product of disulfiram, was an inhibitor of P450IIE1 activity in vitro , and upon preincubation with microsomes, it produced an NADPH-dependent inactivation of NDMA demethylase activity. The results suggest that this or other metabolites of disulfiram are inhibitors of P450IIE1 and are responsible for the inactivation of P450IIE1 in vivo . Hepatotoxicity of NDMA or CCl 4 in rats was blocked by pretreatment with disulfiram. The present work demonstrates that P450IIE1 was inhibited and inactivated by disulfiram, and this mechanism can account for many of the reported inhibitory actions of disulfiram against chemically induced toxicity and carcinogenesis.
Haptics in augmented reality

An augmented reality system merges synthetic sensory information into a user's perception of a three-dimensional environment. An important performance goal for an augmented reality system is that the user perceives a single seamless environment. In most augmented reality systems the user views a real world augmented only with visual information and is not provided with a means to interact with the virtual objects. We describe an augmented reality system that, in addition to visual augmentation, merges synthetic haptic input into the user's perception of the real environment. Our system uses a PHANToM/sup TM/ haptic interface device to generate the haptic sensory input in real-time. The system allows user interactions such as moving or lifting a virtual object, and demonstrates interactions between virtual and real objects. Methods to provide proper visual occlusion between real and virtual objects are also described.
Present and Future Applications of Ultrasonics in Biomedicine

The current importance of ultrasonic energy for the investigation and modification of biological systems is reviewed and the immediately foreseeable potential apparent to the author is predicted. The uses of ultrasound in basic research studies of biological systems and medical applications are conveniently grouped into two major categories: passive uses, or those in which the acoustic field does not significantly modify either permanently or temporarily structure and/or function of the system, and active uses, or those in which modification of the system is the objective. Included within the first category are: absorption spectroscopy of solutions of macromolecular species, microscopy of cells and tissues, absorption characteristics of gross tissue, and visualization of soft tissue structure and its dynamics. The second category includes: the use of ultrasound in neuroanatomical and neurophysiological studies and the treatment of neurological disorders by the production of selective permanent or temporary changes in arrays of sites in the central nervous system, destruction of carcinogenic tissue, modification of endocrine glands, investigation of contractile and other properties of muscle, and the potentiation of ionizing radiation by simultaneous application of ultrasound. Applications of ultrasound in the biomedical field of a primarily technological nature are either mentioned only briefly or omitted entirely from the review. The "socioeconomic" factors which determine the level of financial support, and thus the rate of scientific progress, for a field are also briefly mentioned.
Social language network analysis

In this note we introduce a new methodology that combines tools from social language processing and network analysis to identify socially situated relationships between individuals, even when these relationships are latent or unrecognized. We call this approach social language network analysis (SLNA). We describe the philosophical antecedents of SLNA, the mechanics of preprocessing, processing, and post-processing stages, and the results of applying this approach to a 15-month corporate discussion archive. These example results include an explicit mapping of both the perceived expertise hierarchy and the social support / friendship network within this group.
Comparison of epoxy resins for applications in light-emitting diodes

Epoxy resin is a material commonly used for the encapsulation of light-emitting diodes (LED). Three epoxy resins were chosen in this study: D.E.R.-331 was a bisphenol A type epoxy resin, Eporite-5630 was a bisphenol A type epoxy resin modified with a UV stabilizer, and ERL-4221 was a cyclo-aliphatic epoxy resin. The curing agent was methyl hexahydrophthalic anhydride (MHHPA), and the catalyst was tetra-butyl ammonium bromide (TBAB). Thermal, environmental, and optical properties of the cured epoxy resins were studied. It was found that cured ERL-4221 had better UV resistance, but other properties of ERL-4221 were lower because of the internal stress generated during the curing process. D.E.R.-331 showed better thermal stability, but the aromatic groups in the main chains caused sensitivity to photodegradation. Eporite-5630 had the advantages of D.E.R.-331 and better UV resistance than D.E.R.-331 because of the addition of UV stabilizer. Among the three materials, Eporite-5630 was the best choice of the balance properties for LED applications. This finding may assist in the selection of epoxy resins used in LED technology. © 2004 Wiley Periodicals, Inc. Adv Polym Techn 23: 298–306, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20018
Resolving Alaska and West Coast oil dispersant issues

Agencies and spill responders are currently deliberating about the efficacy of pre-approving the use of dispersants to treat oil slicks in nearshore and shallow waters of the U.S. West Coast and Alaska. The decisions rest on understanding the effectiveness of dispersant operations, the long-term fate and effects of dispersed oil, and the effects of oil slicks and shoreline oiling on critical fisheries and marine species. Processes and knowledge leading to this critical decision point are briefly reviewed.
Performance assessment of the SPDI subsurface imaging technique

Summary form only given.The ability of the spectral and polarization difference imaging (SPDI) technique to provide deep subsurface imaging in tissues is evaluated. The SPDI technique utilizes the wavelength dependence of the mean visit depth of photons inside a tissue sample before they emerge in the backscattered direction. Polarization filtering is used to discriminate against reflected photons from the superficial tissue layers. In addition, this technique involves subtraction of the perpendicular polarization image components obtained under polarized illumination at different wavelengths following appropriate adjustment of the time of exposure in order to normalize the number of photons backscattered from the outer tissue layers. This operation leads to a new image arising from photons that propagated deeper into the tissue which are contained in larger numbers in the image obtained using the longer illumination wavelength.
Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

As a result of overlapping morphologic and immunohistochemical features, it can be difficult to distinguish synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma/primitive neuroectodermal tumor in core biopsies. To analyze and compare immunohistochemical profiles, we stained tissue microarrays of 23 synovial sarcomas, 23 malignant peripheral nerve sheath tumors, and 27 Ewing sarcomas with 22 antibodies potentially useful in the differential diagnosis, and analyzed the data with cluster analysis. Stain intensity was scored as none, weak, or strong. For CD99, tumors with membranous accentuation were independently categorized. Cluster analysis sorted five groups, with like tumors clustering together. Synovial sarcoma clustered into two groups: one cytokeratin and EMA positive (n=11), the other mostly cytokeratin negative, EMA positive, bcl-2 positive and mostly CD56 positive (n=9). Malignant peripheral nerve sheath tumor clustered into two groups: one S100 positive, with nestin and NGFR positivity in most (n=10), the other mostly S100 negative, and variably but mostly weakly positive for nestin and NGFR (n=11). Ewing sarcomas clustered into a single group driven by membranous CD99 staining. Thirteen cases failed to cluster (outliers), while three Ewing sarcomas clustered into groups of other tumor types. Paired antibodies for each tumor type determined by visual assessment of cluster analysis data and statistical calculations of specificity, sensitivity, and predictive values showed that EMA/CK7 for synovial sarcoma, nestin/S100 for malignant peripheral nerve sheath tumor, and membranous CD99/Fli-1 for Ewing sarcoma yielded high specificity and positive predictive values. Cluster analysis also highlighted aberrant staining reactions and diagnostic pitfalls in these tumors. Hierarchical cluster analysis is an effective method for analyzing high-volume immunohistochemical data.
Security vulnerabilities in command and control interoperability

We outline issues associated with communication system interoperability, the security vulnerabilities associated with improved interoperability, network simulation to support the evaluation of the effects of worm-induced packet storms and the experimental design, implementation and results using the OPNET simulation environment.
Wigner distribution for radar waves incident upon a metallic half-space

A plane monochromatic electric field incident upon a metallic interface is analyzed by way of the space-time Wigner distribution. An exact calculation is made and we discuss the behavior of the Wigner distribution at the boundary and inside the metal.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Managing European corn borer resistance to Bt corn with dynamic refuges

Genetically engineered Bt (Bacillus thuringiensis) corn provides farmers with a new tool for controlling the European corn borer (ECB). The high efficacy and potential rapid adoption of Bt corn has raised concerns that the ECB will develop resistance to Bt. The Environmental Protection Agency has responded to these concerns by requiring farmers to plant refuge corn. Current refuge requirements are based on models that do not consider the value of dynamically varying refuge in response to increased scarcity and diminished control over time or the importance of backstop technologies currently being developed. The purpose of this chapter is to evaluate dynamically optimal refuge requirements with the arrival of alternative backstop technologies and to compare the results to an optimal static refuge policy. The results show that a dynamically optimal refuge requirement provides only modest benefits above a static optimum. The results also show how the type of backstop technology and characteristics of ECB population dynamics affect the optimal refuge requirement.
Cell growth rate regulates expression of group B Streptococcus type III capsular polysaccharide.

The capsular polysaccharide (CPS) of group B streptococci (GBS) is an important virulence factor that also serves to protect cells from nonspecific host defense mechanisms. Expression of CPS by GBS, as with other encapsulated bacterial pathogens, is not constitutive but varies during growth in vitro and in primary cultures isolated from different sites of infection. Despite this understanding, little is known about regulation of this surface-expressed carbohydrate antigen in GBS. Here we report that expression of type III CPS by GBS strain M781 grown in continuous culture with a modified chemically defined medium is regulated by growth rate. Cells in steady state at mass doubling times (tds) of 0.8, 1.4, and 1.6 h expressed an average of sixfold more cell-associated CPS than did cells held at tds of 2.3 and 11 h. Strain M781 grown at a td of 1.4 h repeatedly produced more type III CPS than those held at a td of 11.0 h, even when limited for glucose, pyridoxamine, or thiamine. In our studies, > or = 93% of the total CPS expressed by strain M781 was cell associated. Strain M781 grown at a td of 11.0 h (i.e., lowered CPS expression) was susceptible to in vitro complement-mediated opsonophagocytosis and killing by human peripheral blood leukocytes, whereas cells grown at a td of 1.4 h (i.e., higher CPS expression) were not killed unless type III CPS-specific antibody was present. Factors that allow GBS to asymptomatically colonize women yet cause invasive infection to both mother and infant are poorly understood. Our results shed new light on parameters that regulate the pathogenic potential of GBS and may also serve as a way to discern more fully the genetics and biochemistry of GBS capsule synthesis.
Robust controller design for time-varying systems

Examines the design of feedback control systems for linear, time-varying systems. The design procedure is developed using a frequency domain description of a linear, time-varying system and the solution of the H/sub /spl infin// optimal control problem. In particular, design guidelines are derived for several basic performance and robustness objectives. These guidelines reflect the time dependence of the frequency response of a linear, time-varying system while retaining the frequency domain intuition of the time-invariant case. This procedure is analogous to the loop shaping design procedure of McFarlane and Clover (1989) for linear, time-invariant systems.
Violence, Homelessness, and HIV Risk Among Crack-Using African-American Women

This study compares the characteristics of out-of-treatment, homeless, crack-using African-American women with those who are not homeless to determine what risks and protective factors differentiat...
Object-based commutativity analysis for real-time applications

The semantic specification of an object's methods can be used to determine their commutativity properties. The commutative method group, introduced in our earlier work, captures these commutativity properties in terms of groups of methods that commute, as opposed to pairs of methods. This paper outlines how method group commutativity can be used to increase concurrency in distributed and real-time applications. This paper presents the conceptual foundations of our analysis techniques for determining group commutativity. We show that our formal analysis techniques are able to derive a greater degree of commutativity when the semantics of object methods are weakened. This formal procedure is supported by the PVS theorem prover. Using a set of examples, we demonstrate the effectiveness of our approach in detecting increased commutativity when object semantics are weakened.
The Importance of Adjuvant Formulation in the Development of a Tuberculosis Vaccine

An effective protein-based vaccine for tuberculosis will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including alum and the oil-in-water-based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmithKline Biologics), AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants in approved products is AS04, which combines monophosphoryl lipid A, a TLR-4 agonist, with alum. In this study, we compared two adjuvants: a stable oil-in-water emulsion (SE) and a stable oil-in-water emulsion incorporating glucopyranosyl lipid adjuvant, a synthetic TLR-4 agonist (GLA-SE), each together with a recombinant protein, ID93. Both the emulsion SE and GLA-SE adjuvants induce potent cellular responses in combination with ID93 in mice. ID93/SE induced Th2-biased immune responses, whereas ID93/GLA-SE induced multifunctional CD4(+) Th1 cell responses (IFN-γ, TNF-α, and IL-2). The ID93/GLA-SE vaccine candidate induced significant protection in mice and guinea pigs, whereas no protection was observed with ID93/SE, as assessed by reductions in bacterial burden, survival, and pathology. These results highlight the importance of properly formulating subunit vaccines with effective adjuvants for use against tuberculosis.
Inactivation of c-Yes tyrosine kinase by elevation of intracellular calcium levels.

Abstract We have previously shown that the c-Src tyrosine kinase is activated four- to fivefold when cultured keratinocytes differentiate following the elevation of intracellular calcium levels. In contrast to c-Src, another Src family tyrosine kinase, c-Yes, was rapidly inactivated in these same cells, despite its marked similarity in structure and enzymatic activity to c-Src. The inactivation of c-Yes was independent of the protein kinase C pathway, which is usually activated by elevation of intracellular calcium levels. The protein levels of c-Src and c-Yes were not altered, but the phosphotyrosine content of both proteins was greatly reduced. As has been demonstrated for c-Src, in vitro dephosphorylation of c-Yes by incubation with protein tyrosine phosphatases also resulted in its activation, not inactivation. In vitro reconstitution experiments showed that c-Yes can be inactivated by preincubation with a Ca(2+)-supplemented cell extract and that this inhibition was reversed by the addition of EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid]. Gradient sedimentation of cell lysates showed that in cells treated with calcium and ionophore, c-Yes formed complexes with two distinct cellular proteins, whereas similar complexes were not seen in c-Src immunoprecipitates. One of these two proteins has the ability to inhibit c-Yes kinase activity in vitro. Finally, the Ca(2+)-dependent inactivation of c-Yes was observed in kidney tubular cells and fibroblasts, suggesting that the Ca(2+)-dependent regulation of c-Yes tyrosine kinase is not unique to keratinocytes. We postulate that c-Yes is inactivated through a Ca2+ -dependent association with cellular proteins, which seems to override its activation resulting from tyrosine dephosphorylation.