cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparison of gas sensor performance of SnO2 nano-structures on microhotplate platforms

Abstract Metal oxide nano-structures on microhotplate platforms have attracted a great deal of interest in gas sensor research for their potential to create both highly responsive and extremely portable gas sensors. Much of the current research on these sensors has focused upon the creation of hierarchical nanostructures, as van der Waals attraction between nanoparticles leads to agglomeration that impair sensor performance. In this research article, ink-jet printing onto microhotplates was explored as a method of avoiding nanoparticle agglomeration to produce an open film microstructure. Scanning electron microscopy was used to study the deposited thin nanoparticle film featuring an open microstructure free of large agglomeration. Sensor response and response times of ink-jet printed SnO2 nanoparticles were found to be comparable to hierarchical particle films when exposed to methane and carbon monoxide in a background of dry air. Both the SnO2 nanoparticles and microspheres had superior response compared to SnO2 micron-size particles due to increased surface area of the nano-structures. This implies that proper control of the microstructure of the SnO2 nanoparticle films produces similar gas sensor performance to SnO2 hierarchical structures and has the potential for use in reproducibly manufacturing high-performance gas sensors.
A comparative study of the effects of five general anesthetics on myocardial contractility. I. Isometric conditions.

Isolated cat papillary muscles driven at a rate of 12 beats/min at 37.5 C were exposed tojeoncen-trations of cyclopropane, diethyl ether, Ethrane, halothanc, and methoxyflurane similar to those required to produce general anesthesia m vivo. Each anesthetic depressed peak developed ten-sion, maximal dp/dt, and the force-time integral of the twitch, and each shortened the time to peak tension. These variables were altered in qualitatively similar ways by all anesthetics tested, implying a common mode of action on the con-tractile process. When administered in cquieffec-tivc concentrations from the standpoint of producing general anesthesia (i.e at equal MAC's), the order of activity of the anesthetics in depressing contractility (from most to least depressant) was: Ethrane > halothanc > methoxyflurane > cyclopropane > diethyl ether.
Near Infrared Dyes as Lifetime Solvatochromic Probes for Micropolarity Measurements of Biological Systems

The polarity of biological mediums controls a host of physiological processes such as digestion, signaling, transportation, metabolism, and excretion. With the recent widespread use of near-infrared (NIR) fluorescent dyes for biological imaging of cells and living organisms, reporting medium polarity with these dyes would provide invaluable functional information in addition to conventional optical imaging parameters. Here, we report a new approach to determine polarities of macro- and microsystems for in vitro and potential in vivo applications using NIR polymethine molecular probes. Unlike the poor solvatochromic response of NIR dyes in solvents with diverse polarity, their fluorescence lifetimes are highly sensitive, increasing by a factor of up to 8 on moving from polar to nonpolar mediums. We also established a correlation between fluorescence lifetime and solvent orientation polarizability and developed a lifetime polarity index for determining the polarity of complex systems, including micelles and albumin binding sites. Because of the importance of medium polarity in molecular, cellular, and biochemical processes and the significance of reduced autofluorescence and deep tissue penetration of light in the NIR region, the findings reported herein represent an important advance toward using NIR molecular probes to measure the polarity of complex biological systems in vitro and in vivo.
Validation of a method for the determination of zolpidem in human plasma using LC with fluorescence detection

Abstract A sensitive and selective high-performance liquid chromatography (HPLC) method was developed for the determination of zolpidem in human plasma. Zolpidem and the internal standard (trazodone) were extracted from human plasma that had been made basic. The basic sample was loaded onto a conditioned Bond Elut C18 cartridge, rinsed with water and eluted with methanol. Forty microliters were then injected onto the LC system. Separation was achieved on a C18 column (150×4.6 mm, 5 μm) with a mobile phase composed of acetonitrile:50 mM potassium phosphate monobasic at pH 6.0 (4:6, v/v). Detection was by fluorescence, with excitation at 254 nm and emission at 400 nm. The retention times of zolpidem and internal standard were approximately 4.7 and 5.3 min, respectively. The LC run time was 8 min. The assay was linear in concentration range 1–400 ng/ml for zolpidem in human plasma. The analysis of quality control samples for zolpidem (3, 30, and 300 ng/ml) demonstrated excellent precision with relative standard deviations (RSD) of 3.7, 4.6, and 3.0%, respectively ( n =18). The method was accurate with all intraday ( n =6) and overall ( n =18) mean concentrations within 5.8% from nominal at all quality control sample concentrations. This method was also performed using a Gilson Aspec XL automated sample processor and autoinjector. The samples were manually fortified with internal standard and made basic. The Aspec then performed the solid phase extraction and made injections of the samples onto the LC system. Using the automated procedure for analysis, quality control samples for zolpidem (3, 30, and 300 ng/ml) demonstrated acceptable precision with RSD values of 9.0, 4.9, and 5.1%, respectively ( n =12). The method was accurate with all intracurve ( n =4) and overall ( n =12) mean values being less than 10.8% from nominal at all quality control sample concentrations.
Does personality at college entry predict number of reported pain conditions at mid-life? A longitudinal study.

Abstract The purpose of this study was to evaluate whether personality traits, as assessed by the Minnesota Multiphasic Personality Inventory (MMPI), at time of college entry can predict the number of reported pain conditions at an approximate 30-year follow-up for 2332 subjects, 1834 men and 498 women, who were administered the MMPI on entry to the University of North Carolina (Chapel Hill) between 1964 and 1966. In 1997, a follow-up was conducted in which subjects were administered a self-report questionnaire regarding whether they had experienced 1 or more chronic pain conditions. Analyses of the relationship between the MMPI clinical scales at college entrance and the report of number of chronic pain conditions at follow-up were conducted. Among male participants, elevations of Scales 1 (Hypochondriasis), 3 (Hysteria), and 5 (Masculinity/Femininity) predicted increases in number of chronic pain conditions at follow-up. For female participants, elevations in Scales 1, 3, and 6 (Paranoia) predicted increases in number of chronic pain conditions at follow-up. The current study suggests that a statistically significant relationship exists between MMPI responses at college entry and reports of chronic pain conditions at mid-life. Perspective This study found a small, but significant relationship between elevations on MMPI scales measuring hypochondriasis and hysteria and the report of chronic pain conditions at follow-up. The study is important because it is the first to examine how personality assessed in younger adults relates to the number of chronic pain conditions reported 30 years later.
Motility of fish spermatozoa: from external signaling to flagella response

Abstract For successful fertilization, spermatozoa must access, bind, and penetrate an egg, processes for which activation of spermatozoa motility is a prerequisite. Fish spermatozoa are stored in seminal plasma where they are immotile during transit through the genital tract of most externally fertilizing teleosts and chondrosteans. Under natural conditions, motility is induced immediately following release of spermatozoa from the male genital tract into the aqueous environment. The nature of an external trigger for the initiation of motility is highly dependent on the aquatic environment (fresh or salt water) and the species’ reproductive behavior. Triggering signals include osmotic pressure, ionic and gaseous components of external media and, in some cases, egg-derived substances. Extensive study of environmental factors influencing fish spermatozoa motility has led to the proposal of several mechanisms of activation in freshwater and marine fish. However, the signal transduction pathways initiated by these mechanisms remain clear. This review presents the current knowledge with respect to (1) membrane reception of the activation signal and its transduction through the spermatozoa plasma membrane via the external membrane components, ion channels, and aquaporins; (2) cytoplasmic trafficking of the activation signal; (3) final steps of the signaling, including signal transduction to the axonemal machinery, and activation of axonemal dyneins and regulation of their activity; and (4) pathways supplying energy for flagellar motility.
Discrimination, Subculture, and the Economic Performance of Negroes, Puerto Ricans, and Mexican‐Americans

IN TWO EARLIER PAPERS we developed an econometric model to explain ethnic differences in economic performance.1 While the model explains a considerable proportion of the variance among groups, its predictions about the achievement of urban racial minorities are substantial overestimates. Although racial discrimination may account for part of the underachievement of Negroes, Puerto Ricans, and Mexican-Americans, the subculture of these groups and discrimination against this subculture may also contribute. I
Can Machines Adequately Simulate Human Emotion?: A Test of Four Theories of Emotion

In the spirit of the Turing test, machines modeled on four theories of emotion are placed in a naturalistic thought experiment and their ability to simulate human emotion is evaluated. Four simulat...
A practical DCT based blind image watermarking scheme for print-and-scan process

Blind image watermarking technologies allow information to be embedded in common digital images and then recover from the watermarked images without the original images. However, the embedded information is often damaged after the print-and-scan process, because of the randomly added noises, the altered color, and the rotation and scaling introduced in the process. In this paper, we present a practical blind image watermarking scheme based on DCT domain which can survive from the print-and-scan process. The image is partitioned into blocks, and each block embeds one bit watermark data. Two uncorrelated pseudo random sequences are used to spread bit 0 and 1 in the middle frequency band of block-DCT spectrum respectively, which is done by adding the corresponding pseudo random sequence to the middle frequency block-DCT coefficients adaptively. The embedded bit is recovered by comparing the correlations of the modified middle frequency coefficients with each pseudo random sequence. Experiments show that the bit error ratio of watermarking is 2.26% after the print-and-scan process, which is robust enough for visual objects embedding. The robustness of the embedded data can be further improved by incorporating data error correction coding and data repetition voting techniques. In conclusion, this scheme achieves a good performance of both watermark robustness and watermark transparency for the print-and-scan process.
Computer-CT planning of the electron boost om definitive breast irradiation

Treatment planning of the electron boost in breast irradiation at this institution is performed by using information from CT scanning and from surgical clips used to define the tumor bed. A refinement of this technique, taking into account the surgical axis of approach, using computer-CT planning is now implemented. The location of the scar and the clips are digitized using a computer to define the tumor bed dimensions. With 3-D computer software a line, simulating the surgical axis and the central ray of the electron beam, is drawn between the deepest clip and the surgical scar. This beam's eye view along the surgical axis is projected onto a screen as a starting point. Appropriate gantry angle, treatment table position, beam energy, and precise shaping of the electron field borders with a 2 cm margin around the clips and the scar are determined. Simulation films comparing clinically set-up fields and computer-CT planned fields were reviewed. In only 5 of 17 patients did the clinically set-up field have adequate inclusion of the tumor bed within the treatment volume. Computer-CT planned fields ensured adequate inclusion of the tumor bed in all, including the remaining 12. In 7 patients obvious increased sparing of normal breast tissue was seen with computer-CT planned fields. This technique enables accurate placement of a shaped electron field and further refinement of electron boost treatment planning. This is especially true in situations in which the tumor bed is located at a site distant from the lumpectomy scar rather than directly beneath it and in cases where the tumor bed lies deep within the breast.
Classical conditioning with brain stimulation at one site serving as both CS and US

Abstract Cats with chronic electrodes in the inferior colliculus received paired presentations of a weak (CS) and a strong (US) electrical stimulus delivered through the same electrode. After 140–200 such pairings, the weaker stimulus was able to elicit a close approximation to the unconditioned motor response elicited by the stronger stimulus. The response eventually elicited by the weaker stimulus was seen to extinguish following a series of presentations of the weaker stimulus alone. Additional animals receiving the same number of unpaired presentations of the weak and strong electrical stimuli failed to acquire the tendency to make a motor movement in the presence of the weak stimulus. The weak electrical stimulus coming to evoke a response originally elicited only by a stronger stimulus was explained on the basis of classical conditioning rather than pseudoconditioning or sensitization.
A New Piece to the Unsolved Planar Cell Polarity Puzzle

Wnt-Frizzled/Planar cell polarity (PCP) signaling is a conserved mechanism establishing cellular orientation across animal species. Many aspects of PCP-signaling regulation remain, however, poorly understood. A new paper establishes a potential link from Wnt5a to asymmetric PCP-factor localization via their phosphorylation.
Delayed increase of cell volume of single pyramidal cells in live rat hippocampal slices upon kainate application.

Abstract Cell volume is an important physiologic parameter but is not directly accessible by conventional microscopy in vivo or in slice preparations. After staining of rat hippocampal slices with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylinso-carbocyanineperchlorate (DiI), living single CA1 pyramidal cells were visualized by confocal microscopy while others in the illuminated area were recorded intracellularly. Resting membrane potential and action potentials were not affected by staining with DiI (4 μM) and repeated laser illumination (up to 600 times). A time- and dose-dependent increase of cell volume succeeds membrane depolarization upon bath application of kainate (40 μM and 100 μM) with a delay of several minutes indicating active regulation of cell volume. We conclude that cell swelling as visualized by confocal microscopy is a relatively late event of kainate excitotoxicity.
Preliminary 10Be chronology for the last deglaciation of the western margin of the Greenland Ice Sheet

The now acknowledged thinning of the Greenland Ice Sheet raises concerns about its potential contribution to future sea level rise. In order to appreciate the full extent of its contribution to sea level rise, reconstruction of the ice sheet's most recent last deglaciation could provide key information on the timing and the height of the ice sheet at a time of rapid climate readjustment. We measured 10Be concentrations in 12 samples collected along longitudinal and altitudinal transects from Sisimiut to within 10 km of the Isunguata Sermia Glacier ice margin on the western coast of Greenland. Along the longitudinal transect, we collected three perched boulders and two bedrocks. In addition, we sampled seven perched boulders along a vertical transect in a valley within 10 km of the Isunguata Sermia Glacier ice margin. Our pilot dataset constrains the height of the ice sheet during the Last Glacial Maximum (LGM) between 500 m and 840 m (including the 120 m relative sea level depression at the time of the LGM, 21 ka BP). From the transect we estimate the thinning of the ice sheet at the end of the deglaciation between 12.3 ± 1.5 10Be ka (n = 2) and 8.3 ± 1.2 10Be ka (n = 3) to be ∼6 cm a−1 over this time period. Direct dating of the retreat of the western margin of the Greenland Ice Sheet has the potential to better constrain the retreat rate of the ice margin, the thickness of the former ice sheet as well as its response to climate change. Copyright © 2008 John Wiley & Sons, Ltd.
Linear temperature-dependence of penetration depth due to phase fluctuations

Abstract We describe a simple model to estimate the effects of order parameter phase fluctuations on the penetration depth of high-T c superconductors. Classical phase fluctuations are found to produce a linear temperature-dependence of the penetration depth, which may be comparable to the experimentally observed magnitude. We also study how this behavior is modified when the phase fluctuation energy is treated quantum-mechanically.
On the determination of finite integral transforms for forced vibrations of circular plates

Abstract A method for determining a finite integral transform which will remove the presence of one of the independent variables in a fourth-order partial differential equation is applied to the equation of motion of classical plate theory for complete and annular circular plates subjected to various boundary conditions. Special cases of symmetric and non-symmetric loadings are discussed. The method is especially useful for the solution of plate vibration problems with time-dependent boundary conditions.
Prognostic value of p53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder

Objectives. To determine whether molecular and histopathologic tumor features can predict disease progression in Stage T1 transitional cell carcinoma of the bladder. Methods. Tumor specimens from 43 patients were analyzed with respect to grade, presence of carcinoma in situ, invasion deep or superficial to the lamina propria’s muscularis mucosa, p53 expression using DO-7 and PAb1801 antibodies, age, and sex. Flow cytometry was performed on 30 patients from whom there was adequate paraffin-embedded tissue to assess DNA ploidy. Seven patients underwent immediate cystectomy as primary treatment and 36 patients retained their bladders and were at risk of recurrence and progression. Results. The median follow-up was 79 months. Disease recurred in 17 patients (47.2%) and progressed in 6 (16.7%). Only 3 patients (7.0%) died of bladder cancer. None of the parameters investigated was statistically significant in predicting recurrence, progression, or survival. Only carcinoma in situ approached statistical significance (P = 0.0593) as a predictor of progression. Early cystectomy did not have a significant effect on cancer-specific survival (P = 0.3603). The concordance rate between the two p53 antibodies was 88% (P <0.0001). Conclusions. Deep invasion of the lamina propria, p53 positive immunohistochemistry, high grade, and aneuploidy were not significant adverse prognostic factors for either disease progression or survival. Carcinoma in situ associated with Stage T1 transitional cell carcinoma may represent a biologically more aggressive cancer requiring early definitive therapy, but this hypothesis should be evaluated in prospective clinical studies.
Infants' discrimination of vocal expressions: Contributions of auditory and visual information

Abstract Infants 5 months of age have been found to discriminate happy and sad vocal expressions. The present experiment showed that they can discriminate happy and angry vocal expressions as well, but that the presence of a facial expression plays a role in successful discrimination. Infants were visually habituated to a vocal expression accompanied by an affectively matching facial expression, an affectively mismatching facial expression, or a checkerboard pattern. At criterion, the vocal expression was or was not changed while the slide remained the same. Infants who received no change or who had been habituated to a vocal expression accompanied by a checkerboard display failed to dishabituate on the posttests. Infants who received a change in vocal expression from happy to angry or sad, or angry to happy or sad increased their looking time. These results indicate that 5-month-olds can discriminate vocal expressions of emotion when those expressions are presented in conjunction with a face.
Sensitivity of the IceCube neutrino detector to dark matter annihilating in dwarf galaxies

In this paper, we compare the relative sensitivities of gamma-ray and neutrino observations to the dark matter annihilation cross section in leptophilic models such as have been designed to explain PAMELA data. We investigate whether the high energy neutrino telescope IceCube will be competitive with current and upcoming searches by gamma-ray telescopes, such as the Atmospheric Cerenkov Telescopes (H.E.S.S., VERITAS, and MAGIC), or the Fermi Gamma-Ray Space Telescope, in detecting or constraining dark matter particles annihilating in dwarf spheroidal galaxies. We find that after 10 years of observation of the most promising nearby dwarfs, IceCube will have sensitivity comparable to the current sensitivity of gamma-ray telescopes only for very heavy (m_X ≳ 7 TeV) or relatively light (m_X ≲ 200 GeV) dark matter particles which annihilate primarily to μ^+μ^-. If dark matter particles annihilate primarily to τ^+τ^-, IceCube will have superior sensitivity only for dark matter particle masses below the 200 GeV threshold of current Atmospheric Cerenkov Telescopes. If dark matter annihilations proceed directly to neutrino-antineutrino pairs a substantial fraction of the time, IceCube will be competitive with gamma-ray telescopes for a much wider range of dark matter masses.
Evaluation of a physics-based distributed hydrologic model for flood forecasting

Abstract A fully distributed, physics-based rainfall–runoff model called r.water.fea is applied within the Distributed Model Inter-comparison Project (DMIP) organized by the US National Weather Service. Simulations are performed for two basins, the Illinois River and Blue River in Oklahoma. The r.water.fea model is an event-based model that derives parameters and is calibrated using geospatial data. Longstanding research on the Blue and Illinois River basins resulted in a calibrated model using eight events. In order to draw statistical comparisons, the number of events was augmented for the purposes of DMIP. Model performance is evaluated for the Blue and Illinois for the initial and augmented set of storm events. An important finding related to the stability of calibrated parameters from the original 8 to 18-event storm series was observed. As more events were added to expand the number of storms, parameter values changed only slightly. Beyond the calibration phase, a verification period was also used to test the validity of the calibrated parameters. Consistent results were found between the calibration and verification period. In fact prediction accuracy was better in some cases during the verification period, which adds to the confidence in the calibrated model predictions and the methodology. Interior points are used to identify internal model consistency and achievable accuracy. At the interior points located at Watts and Savoy, predictions were biased at Savoy but had better R2 values than obtained at Tahlequah in terms of volume and peak. Watts had comparable bias and nearly identical prediction accuracy compared to Tahlequah. During the verification period for the Blue and Illinois, volume predictions had an accuracy of RMSE=17 and 19 mm. Peak discharge in the two basins was predicted with an accuracy of RMSE=105 and 292 m3/s, respectively. Closer agreement in volume than peak or timing was found in both watersheds, which may indicate the need for improved channel characteristics and routing. The peak discharge predictions achieved by this model in the Illinois during the verification period are biased towards over-prediction by 16% with an R2 of 0.716. Peak discharge prediction accuracy in the Blue River during the verification period is biased towards under-prediction by 13% with an R2 of 0.438. The performance demonstrates that geospatial data may be used to parameterize and calibrate a fully distributed physics-based model, and is capable of making reliable predictions at the outlet and at some interior points.
Regulatory properties of lysine-sensitive aspartokinase under equilibrium conditions.

Abstract The regulatory properties of the lysine-sensitive aspartokinase (ATP : l -aspartate 4-phosphotransferase, EC 2.7.2.4) have been studied under equilibrium conditions by determining the effects of modifiers on the rate of equilibrium isotope exchange between ADP and ATP. The extent of inhibition by lysine, leucine or phenylalanine is almost independent of substrate concentration but is influenced by the substrate/product ratio. Inhibition by a given concentration of inhibitor is increased when the ADP/ATP ratio is increased indicating a regulatory interaction between end products and cellular energy metabolism. Lysine inhibition is cooperative under equilibrium conditions and the parameters of the Hill equation are nearly identical to those obtained in initial velocity studies. A cooperative heterotropic interaction between lysine and leusine is also observed by the ATP-ADP exchange assay just as it is in initial velocity assays. Thus, the regulatory features of aspartokinase that are observed in initial velocity studies are also manifest under equilibrium conditions as revealed by equilibrium isotope exchange rates.
A 0.28THz 4×4 power-generation and beam-steering array

Up until recently, the terahertz frequency range (0.3 to 3THz) has been mostly addressed by high-mobility custom III-V processes, bulky and expensive nonlinear optics, or cryogenically cooled quantum cascade lasers. A low-cost room temperature alternative will enable a wide range of applications in security, defense, ultra-high-speed wireless communication, sensors, and biomedical imaging not currently accessible due to cost and size limitations. CMOS can potentially provide such a low-cost platform, but it requires novel techniques and architectures to generate, manipulate, radiate, and detect signals above transistor f max , which are in the sub-THz frequency region in most of today's nodes.
Corynebactin and Enterobactin: Related Siderophores of Opposite Chirality

Most species of bacteria employ siderophores to acquire iron. The chirality of the ferric siderophore complex plays an important role in cell recognition, uptake, and utilization. Corynebactin, isolated from Gram-positive bacteria, is structurally similar to enterobactin, a well known siderophore isolated from Gram-negative bacteria, but contains l-theronine instead of l-serine in the trilactone backbone. Corynebactin also contains a glycine spacer unit in each of the chelating arms. A hybrid analogue (serine-corynebactin) has been synthesized. The chirality and relative conformational stability of the three ferric complexes of enterobactin, corynebactin, and the hybrid has been investigated. In contrast to enterobactin, corynebactin assumes a Λ configuration. However, the ferric serine-corynebactin hybrid forms a racemic mixture, only slightly favoring the Λ conformation.
Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving, Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.
A Graphical Approach to the Stiglerian Theory of Regulation

Although many authors have drawn on the basic insights of the early founders of the economic theory of regulation, the ability to cogently present the general form of the theory in a readily accessible graphical format has only recently emerged. Although providing a promising approach for illustrating and analyzing regulatory and deregulatory outcomes, the analysis presented to this point appears to require the derivation of several graphs. The result is that, although stemming from a single paradigmatic framework, the graphical approach fails to offer a single unified basis for illustrating the general economic theory of regulation. The authors seek to fill this lacuna by providing a simple yet powerful unifying graphical construct for presenting the myriad implications of that theory.
Combined gradient-gel electrophoresis procedures for determining buoyant densities or sedimentation coefficients of all multiple forms of an enzyme simultaneously

Abstract Ultracentrifugation of tissue homogenates in linear gradients followed by gel electrophoresis of the individual gradient fractions allows the determination of the buoyant densities (in CsCl) or sedimentation coefficients (in sucrose) for all multiple forms of an enzyme simultaneously. This technique was used in conjunction with density labeling to demonstrate synthesis of the newly appearing isozymes of peroxidase in germinating barley embryos. Similarly the sedimentation coefficients of all these isozymes were determined in a single sucrose gradient.
HER2 regulatory control of angiopoietin-2 in breast cancer

Abstract Background: HER2 overexpression is a marker of aggressive breast cancer. Tumors that overexpress HER2 induce endothelial cell retraction and endothelial destabilization. Because angiopoietin-2 (Ang-2) also destabilizes microvessels, we postulated that HER2 signaling upregulates Ang-2 as a mechanism of angioinvasion. Methods: We tested human breast cancers and breast cancer cell lines for coexpression of HER2 and Ang-2 with Northern blot, reverse transcriptase–polymerase chain reaction, and enzyme-linked immunosorbent assay. Further, we manipulated HER2 signaling with 100 ng/mL MAbHu HER2 (Herceptin; Genentech, San Francisco, Calif) and Heregulin β1 (100 ng/mL; RD 2 cancers expressed only Ang-2. Conclusions: We conclude that human breast cancers express Ang-2. HER2 signaling appears to regulate Ang-2 expression, although other signaling pathways may also regulate Ang-2. Ang-2 may be a therapeutic target in these cancers and may define which patients would benefit from Herceptin therapy. (Surgery 2000;128:153-8.)
Cut Child Benefits to Cut Taxes

Should the well-off benefit from fiscal resources if they choose to have children? Professor Michael Beenstock of the City University Business School argues that they should not. Child Benefit, in common with other fiscal subventions, should be limited to families in most need. Dr lvy Papps in the last issue argued the case for selectivity in Child Benefit. Professor Beenstock's proposal represents a radical departure from the present arrangements under which Child Benefit is universal, regardless of family income, and he calculates the cuts in income tax that could follow. Given the size of his family (above). Professor Beenstock is obviously more interested in economic truth than personal advantage.
General Antimutators are Improbable

Abstract Antimutator mutations reduce spontaneous mutation rates, at least at some sites and along some pathways. Antimutators have been found in several microbial systems since their initial discovery in bacteriophage T4, where they occur mainly among mutations of gene 43 (which encodes the viral DNA polymerase). The phage T4 antimutators are highly specific, often strongly reducing mutations rates but only along specific pathways, usually A·T→G·C. They may fail to affect other pathways, such as G·C→A·T, and may even accelerate mutation at yet other pathways, such as transversions (R·Y→Y·R). Both enzymatic and evolutionary considerations suggest that it should be difficult to isolate strong, general antimutator mutations, that is, mutations that substantially lower the total spontaneous mutation rate over the entire genome without producing strongly deleterious side effects. This notion has been tested by measuring mutation rates over a target comprising several kilobases in a set of phage T4 antimutators. In each case, this rate was indistinguishable from or greater than the wild-type rate. A survey of reports describing antimutators in other microbes reveals that none are yet demonstrated to be general antimutators.
Self-schema priming and desire for test performance feedback: Further evaluation of a cognitive/interactionist model of interpersonal dependency

The cognitive/interactionist (C/I) model of interpersonal dependency contends that two central elements of a dependent personality orientation are a schema of the self as powerless and ineffectual, and a resulting desire to obtain and maintain ties to potential caregivers and protectors. Two experiments tested this aspect of the C/I model. Experiment 1 found that dependency level and schema priming combined to predict the amount of time participants were willing to wait for test performance feedback from a professor. Experiment 2 found that varying the likelihood that the professor would be able to offer future help and support moderated the significant dependency and priming effects obtained in Experiment 1. These results support the C/I model; theoretical and empirical implications are discussed.
Scanning ultrahigh vacuum reflectometer.

A reflectometer is described that extends the continuous measurement of the near-normal-incidence reflectance of solids to vacuum ultraviolet (vuv) wavelengths. Clean reflecting surfaces are achieved by in situ sample preparation and ultrahigh vacuum environment. The low intensity problem is solved with electronic lock-in amplification. The over-all instrument has an absolute error of reflectance of (ΔR/R)Absolute = ±0.03. The precision is estimated to be (ΔR/R)Relative = ±0.002 or better. The wavelength range of 1100 A to 7000 A is covered. Some representative results show that this design provides substantial improvement in sensitivity and resolution of vuv reflectance measurements.
Creation and implementation of a historical controls database from randomized clinical trials.

Background Ethical concerns about randomly assigning patients to suboptimal or placebo arms and the paucity of willing participants for randomization into control and experimental groups have renewed focus on the use of historical controls in clinical trials. Although databases of historical controls have been advocated, no published reports have described the technical and informatics issues involved in their creation. Objective To create a historical controls database by leveraging internal clinical trial data at Pfizer, focusing on patients who received only placebo in randomized controlled trials. Methods We transformed disparate clinical data sources by indexing, developing, and integrating clinical data within internal databases and archives. We focused primarily on trials mapped into a consistent standard and trials in the pain therapeutic area as a pilot. Results Of the more than 20 000 internal Pfizer clinical trials, 2404 completed placebo controlled studies with a parallel design were identified. Due to challenges with informed consent and data standards used in older clinical trials, studies completed before 2000 were excluded, yielding 1134 studies from which placebo subjects and associated clinical data were extracted. Conclusions It is technically feasible to pool portions of placebo populations through a stratification and segmentation approach for a historical placebo group database. A sufficiently large placebo controls database would enable previous distribution calculations on representative populations to supplement, not eliminate, the placebo arm of future clinical trials. Creation of an industry-wide placebo controls database, utilizing a universal standard, beyond the borders of Pfizer would add significant efficiencies to the clinical trial and drug development process.
CYP2C9 Genotype-Dependent Effects on in Vitro Drug-Drug Interactions: Switching of Benzbromarone Effect from Inhibition to Activation in the CYP2C9.3 Variant

The CYP2C9.3 variant exhibits marked decreases in substrate turnover compared with the wild-type enzyme, but little is known regarding the effect this variant form may have on the occurrence of drug-drug interactions. To examine this possibility, the effect of the potent CYP2C9 inhibitor, benzbromarone, was studied with regard to CYP2C9.1- and CYP2C9.3-mediated flurbiprofen metabolism to evaluate whether the variant enzyme exhibits differential inhibition kinetics. Although benzbromarone inhibited CYP2C9.1 activity as expected, CYP2C9.3-mediated flurbiprofen 4'-hydroxylation was activated in the presence of benzbromarone. T1 relaxation studies revealed little change in distances of flurbiprofen protons from the heme iron of either CYP2C9.1 or CYP2C9.3 in the presence of benzbromarone compared with flurbiprofen alone. Spectral binding studies were also performed to investigate whether benzbromarone affected substrate binding, with the addition of benzbromarone having little effect on flurbiprofen-binding affinity in both CYP2C9.1 and CYP2C9.3. Docking studies with the 2C9.1 structure crystallized with a closed active site identified multiple but overlapping subsites with sufficient space for benzbromarone binding in the enzyme when flurbiprofen was positioned closest to the heme. If the closed conformation of 2C9.3 is structurally similar to 2C9.1, as expected for the conservative I359L mutation, then the dynamics of benzbromarone binding may account for the switching of drug interaction effects. In conclusion, the I359L amino acid substitution found in CYP2C9.3 not only reduces metabolism compared with CYP2C9.1 but can also dramatically alter inhibitor effects, suggesting that differential degrees of drug inhibition interactions may occur in individuals with this variant form of CYP2C9.
Stochastic gradient techniques for the efficient simulation of high-speed networks using importance sampling

To obtain large speed-up factors in Monte Carlo simulation using importance sampling (IS), the modification, or bias of the underlying probability measures must be carefully chosen. Analytical optimization techniques are generally ineffective, especially for queueing networks with bursty traffic. The authors present two stochastic gradient optimization techniques that lead to favorable IS parameter settings in the simulation of queueing networks, including queues with bursty traffic. Namely, they motivate and describe the stochastic gradient descent (SGD) algorithm, and the stochastic (important event) frequency ascent (SFA) algorithm. They demonstrate the effectiveness of their algorithms by applying them to the problem of estimating the blocking probability for a queue with two arrival streams, a modified interrupted Bernoulli stream and a Markov modulated Bernoulli stream with batch arrivals, deterministic service times, and finite capacity K (denoted by M-IBP+MMBBP/D/1/K). Speed-up factors of 1 to 6 orders of magnitude over conventional Monte Carlo simulation are achieved for the examples presented. >
Modulation of antigen expression in human tumor cell populations.

(1986). Modulation of Antigen Expression in Human Tumor Cell Populations. Cancer Investigation: Vol. 4, No. 3, pp. 239-256.
A comparison using signal detection theory of the ability of two computational auditory models to predict experimental data

In order to develop improved remediation techniques for hearing impairment, auditory researchers must gain a greater understanding of the relation between the psychophysics of hearing and the underlying physiology. One approach to studying the auditory system has been to design computational auditory models that predict neurophysiological data such as neural firing rates. To link these physiologically-based models to psychophysics, theoretical bounds on detection performance have been derived using signal detection theory to analyze the simulated data for various psychophysical tasks. Previous efforts, including our own recent work using the auditory image model, have demonstrated the validity of this type of analysis; however, theoretical predictions often exceed experimentally-measured performance. In this paper, we compare predictions of detection performance across several computational auditory models. We reconcile some of the previously observed discrepancies by incorporating phase uncertainty into the optimal detector.
Postoperative conduction disturbances: a comparison of blood and crystalloid cardioplegia.

Conduction system disturbances after cardioplegia am well described. Our four-man group changed in mid-1987 from standard crystalloid cardioplegia (35 mEq/L of KCl) to blood cardioplegia 44 parts blood to 1 part cardioplegia) (18 mEq/L of KCl) based on experimental and clinical evidence that blood cardioplegia provides better myocardial protection- Shortly thereafter, we anecdotally noted increased conduction abnormalities. This prompted us to compare serially all patients undergoing coronary artery bypass grafting during 1987 for perioperative and late conduction system disturbances after either crystalloid or blood cardioplegia. Surgeons and techniques including topical cooling did not differ. Forty-one (23%) of 179 patients with crystalloid cardioplegia had conduction disturbances versus 141 (49%) of 289 patients with blood cardioplegia ( p p p p p p p p
Measurement of HF monopole antenna array ground wave gain, antenna factor, and antenna noise factor

This paper presents a practical way to measure the ground wave gain G/sub GW/, ground wave antenna factor AF/sub GW/, and antenna noise factor F/sub a/(Mon) of monopoles used in BF antenna arrays. It shows measurement results taken from June 1997 to September 1999 at five geographically separated HIT arrays. F/sub a/(Mon) is derived from site specific noise electric field E/sub n/ and can be compared with "standard" F/sub a/(*). While antenna noise factor is antenna dependent, E/sub n/ is not and can be used as a limit for site EMC with noise emitters.
The detachment era (1977–1982) and its role in revolutionizing continental tectonics

After the discovery of thrust-and-nappe structure near the turn of the twentieth century, mountain belts were viewed as a direct expression of horizontal shortening of the continental crust, and continental rifting was viewed as a phenomenon distinct from it. By mid-century, broad consensus had emerged, mainly on the basis of physical reasoning, that thrust-and-nappe structure instead reflected gravity sliding secondary to vertical motions of the crust, as embodied in the influential stockwerk folding hypothesis. In a noteworthy period from 1977 to 1982, informally referred to here as the ‘detachment era’, not only did the last vestiges of support for the stockwerk hypothesis evaporate, but large-magnitude extension was discovered throughout the Cordillera, manifest primarily by extensional detachments and metamorphic core complexes. Soon afterward extensional detachments were recognized as a global phenomenon, forcing first-order reinterpretation of field relations in most orogens. Although plate tectonics is indisputably the most profound discovery in Earth sciences in the twentieth century, the detachment era arguably had commensurate impact on field-based interpretations of continental tectonics. Three decades later, controversy persists over the origin of metamorphic tectonites in core complexes, and over the existence and mechanics of slip on shallowly dipping extensional detachments.
Intracoronary ultrasound imaging before and after directional coronary atherectomy: In vitro and clinical observations☆

The rate of restenosis after directional coronary atherectomy (DCA) is higher than expected. To elucidate why, the current study used intravascular ultrasound (IVUS) imaging to investigate the mechanism of DCA. An in vitro validation study was performed to determine the accuracy of the measurement of plaque removal by IVUS. DCA was performed in eight human atherosclerotic artery segments. The volume of removed plaque was measured by water displacement and was compared with the volume calculated from IVUS images. A clinical study of DCA was performed in 32 lesions. IVUS was performed in 28 lesions after successful DCA. Measurements of lumen dimensions from digital angiograms before and after DCA were compared with observations of lumen and plaque size from the cross-sectional IVUS images. In the in vitro study, the mean plaque volume removed by DCA was 19.9 +/- 8.5 microliters. The calculated estimate of removed plaque volume by IVUS was 18.6 +/- 7.9 microliters and correlated closely with the volume by water displacement (r = 0.92). The calculated volume of plaque removed from histologic sections was 14.3 +/- 6.0 microliters and was linearly correlated with plaque volume by water displacement (r = 0.81). In the clinical study, the angiographic mean minimum lumen diameter increased from 1.0 +/- 0.4 to 2.7 +/- 0.5 mm and the percentage stenosis decreased from 70% to 19% (p < 0.0001). The IVUS images before and after DCA showed that the lumen DCA improved from 2.9 +/- 1.5 to 7.0 +/- 1.5 mm2 (p < 0.0001). In addition the vessel cross-sectional area (CSA) increased from 17.1 +/- 5.9 to 18.7 +/- 5.5 mm2. The atheroma CSA was reduced from 14.2 +/- 5.0 to 11.7 +/- 4.8 mm2. This combined effect of reduction in atheroma CSA and stretching of the outer vessel diameter resulted in an improvement in percentage plaque area stenosis from 83% +/- 7% to 61% +/- 9%. It is concluded that despite a successful angiographic appearance, DCA removed an average of 2.5 mm2 from the atheroma, which corresponds to only 18% of the atheroma CSA. The total lumen CSA increased 4.1 mm2; 61% of the new lumen was created by cutting and removal of plaque, whereas 39% of the new lumen was made by stretching the external wall of the artery. Despite an excellent angiographic result, IVUS imaging reveals that after DCA a significant amount of residual atheroma remains. As in balloon dilatation, a stretching effect is a significant component of DCA.