cssi/SciSciGPT-SciSciNet huggingface dataset:
Intracellular Delivery of Antibodies for Selective Cell Signaling Interference

Abstract Many intracellular signaling events remain poorly characterized due to a general lack of tools to interfere with “undruggable” targets. Antibodies have the potential to elucidate intracellular mechanisms via targeted disruption of cell signaling cascades because of their ability to bind to a target with high specificity and affinity. However, due to their size and chemical composition, antibodies cannot innately cross the cell membrane, and thus access to the cytosol with these macromolecules has been limited. Here, we describe strategies for accessing the intracellular space with recombinant antibodies mediated by cationic lipid nanoparticles to selectively disrupt intracellular signaling events. To enable such investigations, we first produced a series of antibody constructs, known as scFv-Fcs, containing additional, genetically encoded negative charges located at the C-termini of the constructs. Preparing proteins with negatively charged motifs has previously been shown to enhance intracellular protein delivery with cationic lipids, but usually for the purpose of genome editing or targeted cell death. We started by generating derivatives of scFv-Fc17, an antibody construct previously reported to bind specifically to signal transducer and activator of transcription 3 (STAT3) phosphorylated at Tyr705 (pYSTAT3). We screened a small number of lipids from our combinatorial lipid library with flow cytometry and found that PBA-Q76-O16B facilitated the most efficient delivery of scFv-Fcs under the conditions tested. In HepG2 cells, we observed up to 60.5% delivery efficacy, while in a STAT3-luciferase reporter cell line up to 71.5% delivery efficacy was observed. These results demonstrated the feasibility of accessing the intracellular space with scFv-Fcs. However, we also note that no more than modest changes were observed upon changing the numbers of negative charges in these constructs during delivery. Characterization of the cytotoxicity, size, and encapsulation efficiency of scFv-Fcs with PBA-Q76-O16B revealed that the constructs were generally well-behaved, with addition of differing quantities of negative charge resulting in at most modest effects. Importantly, functional assays monitoring transcriptional activity in luciferase reporter cell lines and HepG2 cells demonstrated significant reduction of gene expression downstream of pYSTAT3 following delivery of scFv-Fc17 constructs. Together, our results establish the use of recombinantly produced antibodies to selectively interfere with cell signaling events driven by a single posttranslational modification. Efficient intracellular delivery of engineered antibodies opens up possibilities for modulation of previously “undruggable” targets, including for potential therapeutic applications.
Effect of paclobutrazol on accumulation of organic acids and total phenols in apple wood

Apple trees (Malus domestica Borkh “Spartan” grafted on MM 106 rootstock) planted in 1976 in an orchard at Beltsville, Maryland, were treated with paclobutrazol (2RS,3RS)-1-(4-chlorophenyl)-4,4-dimethyl-2-1,2,4-triazol-1-yl-pentan-3-ol) using a foliage spray in 1982 and by trunk banding in 1983. Paclobutrazol did not inhibit shoot growth in 1983; however, shoot growth was significantly retarded in 1984. Increases in organic acids, including succinic, malic, citric, and quinic, and also in total phenols, occurred in wood produced in 1983 on paclobutrazol-treated trees when growth was not inhibited and in wood produced in 1984 when growth was inhibited. The organic acid content of both paclobutrazol-treated and untreated wood tended to decrease from the winter dormant period through growth resumption in the spring. However, the content of total phenols remained nearly the same throughout this sampling period.
Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse

The development of chemical synapses is regulated by interactions between pre- and postsynaptic cells. At the vertebrate skeletal neuromuscular junction, the organization of an acetylcholine receptor (AChR)-rich postsynaptic apparatus has been well studied. Much evidence suggests that the nerve-derived protein agrin activates muscle-specific kinase (MuSK) to cluster AChRs through the synapse-specific cytoplasmic protein rapsyn. But how postsynaptic differentiation is initiated, or why most synapses are restricted to an 'end-plate band' in the middle of the muscle remains unknown. Here we have used genetic methods to address these issues. We report that the initial steps in postsynaptic differentiation and formation of an end-plate band require MuSK and rapsyn, but are not dependent on agrin or the presence of motor axons. In contrast, the subsequent stages of synaptic growth and maintenance require nerve-derived agrin, and a second nerve-derived signal that disperses ectopic postsynaptic apparatus.
Using the standard error of measurement to identify important changes on the Asthma Quality of Life Questionnaire.

Objectives: To establish a link between the minimal important difference (MID) and the standard error of measurement (SEM) for all responsive dimensions of the Asthma Quality of Life Questionnaire (AQLQ). Methods: Secondary data analysis of baseline and follow-up interview data from 198 outpatients with asthma enrolled in a randomized controlled trial and receiving care at a major urban academic medical center's general medicine clinics. Domain statistics for baseline and follow-up interviews were examined for the AQLQ. The baseline SEM values were compared with established AQLQ MID standards using weighted κ values. Results: One SEM identified the MID in responsive AQLQ dimensions. Weighted κ values (0.88–0.93) validated excellent agreement between these two criteria. Conclusion: This is the third study to support using one SEM to identify important individual change in health-related quality of life (HRQoL) measures. However, refinement of the process for determining a measure's clinically meaningful differences is still needed to secure a link between the SEM and the identification of relevant HRQoL change over time.
Structural basis of the allosteric inhibitor interaction on the HIV-1 reverse transcriptase RNase H domain.

HIV-1 reverse transcriptase (RT) has been an attractive target for the development of antiretroviral agents. Although this enzyme is bi-functional, having both DNA polymerase and ribonuclease H (RNH) activities, there is no clinically approved inhibitor of the RNH activity. Here, we characterize the structural basis and molecular interaction of an allosteric site inhibitor, BHMP07, with the wild-type (WT) RNH fragment. Solution NMR experiments for inhibitor titration on WT RNH showed relatively wide chemical shift perturbations, suggesting a long-range conformational effect on the inhibitor interaction. Comparisons of the inhibitor-induced NMR chemical shift changes of RNH with those of RNH dimer, in the presence and absence of Mg2+, were performed to determine and verify the interaction site. The NMR results, with assistance of molecular docking, indicate that BHMP07 preferentially binds to a site that is located between the RNH active site and the region encompassing helices B and D (the ‘substrate-handle region’). The interaction site is consistent with the previous proposed site, identified using a chimeric RNH (p15-EC) [Gong et al. (2011) Chem Biol Drug Des 77, 39–47], but with slight differences that reflect the characteristics of the amino acid sequences in p15-EC compared to the WT RNH.
Hypothesis Filtering: A Practical Approach to Reliable Learning

Abstract This paper shows how to take virtually any learning algorithm and turn it into one which is accurate and reliable to an arbitrary degree. The transformation is accomplished by appending a filter that performs a statistical test to the learning algorithm. The filter only outputs hypotheses that pass the test. The test takes time which is polynomial in the desired accuracy and reliability levels and is independent of the learning algorithm and the complexity of its domain. Distribution-free statistical theory is used to prove that the filter works. We describe the application of the filter to concept learning, and to SE, a system which learns control knowledge by clustering its data. The significance of hypothesis filtering is two fold. First, filters may be used to evaluate and compare the performance of a wide range of learning algorithms. Second, applying hypothesis filtering to inductive learning algorithms demonstrates that the algorithms can be made arbitrarily reliable, and provably so.
Semantic B2B integration server technology as infrastructure for electronic hubs

Electronic hubs are intermediaries that simplify business-to-business (B2B) communication. While communication hubs are focused on managing the events exchanged between trading partners, domain hubs provide semantics like buyer/seller matching in the purchasing process. Hub architectures require functionality that can be provided by B2B integration server technology. This shows that hubs are not a new type of infrastructure but are a particular application of B2B integration server technology.
Clinical outcome of patients with carcinoma ex pleomorphic adenoma of the parotid gland: a comparative study from a single tertiary center.

Background Carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland is a high-grade cancer and the prognosis of this cancer has not been compared with non-CXPA high-grade primary parotid cancer. Methods Retrospective medical chart review of patients with surgically treated high-grade primary parotid cancer (21 CXPA and 52 non-CXPA) was performed with correlation with disease-specific survival, locoregional recurrence, and distant recurrence. Results Despite having similar stage of cancer and extent of surgical resection, patients with CXPA had a lower disease-specific survival compared to non-CXPA high-grade primary parotid cancer (p = .02). Salivary duct cancer (SDC) was the commonest histologic variant in both cohorts and around 40% of patients with SDC died of distant recurrence that occurred within 3 years from diagnosis. Conclusion CXPA of the parotid gland is a more aggressive cancer compared to non-CXPA high-grade primary parotid cancer. SDC was associated with a high chance of delayed distant recurrence, which contributed directly to the mortality of this cancer.
Epitaxial Growth of 4H-SiC with High Growth Rate Using CH3Cl and SiCl4 Chlorinated Growth Precursors

Thick 4H-SiC epitaxial layers have been grown using a combination of two chlorinated precursors silicon tetrachloride (SiCl4) and chloromethane (CH3Cl) at 16000C. Growth rates up to 100 m/hr have been demonstrated. The use of chloro-silane precursor eliminated the problem of homogenous nucleation of Si in the gas phase, which was significant in CH3Cl/SiH4 growth. Much higher values of Si/H2 and C/H2 ratios without morphology degradation were made possible by increasing the growth temperature from 1300 to 1600°C. Results of photoluminescence and high-resolution X-ray diffraction and time-resolved PL were used to evaluate the quality of the epitaxial layers. The crystalline quality and the growth rate achieved so far offer a promise of exceeding the state of the arts results achieved with more traditional hydro-carbon precursors.
EFFECT OF MUSCLE TYPE ON RESIDUAL NITRITE IN CURED MEAT

When a cured meat model system was made from white muscle it contained less residual nitrite than if it were made from a red muscle; this effect is due to the lower pH of white muscle. If the pH of red and white muscle is similar then the slightly lower residual nitrite in products made from red muscle probably is due to the greater content of myoglobin in red muscle.
The rhetorics of policy analysis

This paper claims that policy analysis is inherently rhetorical, that it cannot be fully understood apart from the audiences to which it is directed and the styles in which it is communicated. Defining rhetoric as persuasive discourse within and between interpretive communities, I argue that policy analysts are embedded in a complex rhetorical situation created by the interaction of three primary audiences (scientists, politicians, and lay advocates), each of which has its own normal discourse and agreed-upon conventions of persuasion, and that failure to persuade any one of these audiences will cause analysts to appear incompetent, impractical or illegitimate. To support and illustrate this claim I reconstruct the theoretical literature about policy analysis in rhetorical terms, then review events that occurred at Love Canal, New York, in the late 1970s. I conclude by suggesting that policy analysts need to ‘actively mediate’ the policy discourse between scientists, politicians, and advocates.
The Extinct Wake Island Rail Gallirallus wakensis: A Comprehensive Species Account Based on Museum Specimens and Archival Records

Abstract A review of all available specimens and the discovery of many unpublished life history notes allows a much more complete picture of the morphology and behavior of the extinct Wake Island Rail (Gallirallus wakensis). The breeding season of the species may have been environmentally influenced but, under favorable conditions, there may have been two broods per year. Small groups of birds engaged in cooperative nesting and prolonged parental care and feeding of the young, probably in part to defend the eggs and young from hermit crabs (Coenobita) and rats (Rattus). The smallest species of its genus, the Wake Island Rail was able to co-exist with Pacific rats (Rattus exulans). Extinction of the rail occurred between 1942 and 1945 as a result of direct predation by thousands of starving Japanese troops and habitat destruction resulting from military alterations and aerial bombardment.
Toward a Statistical Description of Finescale Strain in the Thermocline

Abstract The statistical properties of the oceanic finescale strain field are investigated. Strain information is derived from a set of 9000 CTD profiles from the surface to 560-m depth, obtained from the Research Platform FLIP in the 1986 PATCHEX Experiment. Four hundred isopycnals, with mean vertical separation Δz = 1 m, were tracked for the 19-day duration of the experiment. The instantaneous separation, Δz(t), between isopycnal pairs is found to be statistically independent of the mean position of the pair. The separation statistics demonstrate a number of the characteristic features of a Poisson process. If the number of isopycnals found in a given fixed-depth interval is simply tallied from profile to profile, the variability in the count, when properly rescaled, is given by a Poisson distribution. Probability density functions (pdfs) of separation are well described by the classical Gamma family. A simple mechanistic model of the strain field is proposed as a guide for interpreting the Poisson-like...
Refractive lens exchange with intraocular lens implantation in hyperopic eyes of a patient with Angelman syndrome

We describe a patient with Angelman syndrome with severe developmental delay who was visually impaired by uncorrected high hyperopia and poor control of accommodation. Refractive lens exchange with intraocular lens implantation was performed in both eyes when the patient was 22 years of age. Satisfactory anatomical and functional outcomes were achieved and maintained during 3 years of follow-up. Refractive lens exchange can be useful in patients with severe neurobehavioral disorders in the presence of high refractive error and poor accommodative control. Financial Disclosure Neither author has a financial or proprietary interest in any material or method mentioned.
Quantifying the Microstructure of Human Sclera Using Small Angle Light Scattering

The role of mechanical forces in the progression of glaucoma has been suggested to be critical, especially in the region of the lamina cribrosa and optic nerve head [1,2]. However, little is known regarding the quantitative mapping of collagen fiber architecture around the scleral globe. Several experimental investigations into the biomechanical response of ocular tissue from animals [3–5] have been performed while comparatively less information is available for the response of human ocular tissue.Copyright © 2008 by ASME
Climate Data Guide Spurs Discovery and Understanding

Highly accurate and stable observations—beyond those provided by routine weather monitoring—are essential for understanding the behavior of the climate system, developing and validating Earth system models, and attributing extreme weather events and long-term trends to causes [National Research Council, 2012; Trenberth et al., 2013]. In parallel with an exploding volume of climate data, ready access to data in user-friendly formats is important to an expanding number and increasing diversity of individuals worldwide across public, private, and academic sectors [Overpeck et al., 2011].
The x-ray sensitivity of amorphous selenium for mammography.

A study of the x-ray sensitivity of amorphous selenium (a-Se) for digital mammography has been performed. A uniform layer of a-Se was deposited on a glass substrate with electrodes on both surfaces. The deposition procedure was identical to that used for a-Se flat-panel detectors. A high voltage was applied to the top surface of the a-Se layer in order to establish an electric field E(Se). Then the sample was exposed to x rays with 27 kVp spectra generated from an x-ray tube with a molybdenum (Mo) target. The mean x-ray energy of the spectrum used was approximately 16.6 keV. The x-ray current generated by the a-Se layer was measured as a function of E(Se). From the current measurement and the estimation of total x-ray energy absorbed in the a-Se, the energy required to create one electron-hole pair (EHP), W, was determined as a function of E(Se). It was found that at the most commonly used E(Se) of 10 V/microm, W was measured as 64 eV. This is considerably higher than the widely accepted typical value of W = 50 eV measured at higher x-ray photon energies (e.g., 50 keV). The dependence of W as a function of E(Se) can be best fitted using the empirical expression of E(Se)-gamma. This relationship is consistent with the results obtained at higher x-ray energies. This article provides an accurate measurement of x-ray sensitivity of a-Se at mammographic energies independent of detector operation, such as the most recently developed flat-panel detectors. The results will be a useful tool for investigation and optimization of a-Se-based x-ray imaging detectors, such as determination of pixel fill-factor and optimal E(Se) during operation.
HEDONIC PRICES, IDENTIFICATION, AND THE DEMAND FOR PUBLIC SAFETY*

In this paper, we use a two-stage intercity hedonic model to estimate household demand for public safety. This approach is shown to readily address the identification problem inherent in the hedonic model. Data from the 1980 Public Use Microdata Sample are used to estimate a willingness-to-pay function for the public-safety good. Income is found to be the primary determinant of willingness to pay. Indeed, the influence of income outweighs the combined impact of family life-cycle considerations.
Kinetic energy distribution of H(2p) atoms from dissociative excitation of H2.

The kinetic energy distribution of H(2p) atoms resulting from electron impact dissociation of H2 has been measured for the first time with uv spectroscopy. A high resolution uv spectrometer was used for the measurement of the H Lyman-alpha emission line profiles at 20 and 100 eV electron impact energies. Analysis of the deconvolved 100 eV line profile reveals the existence of a narrow line peak and a broad pedestal base. Slow H(2p) atoms with peak energy near 80 meV produce the peak profile, which is nearly independent of impact energy. The wings of H Lyman-alpha arise from dissociative excitation of a series of doubly excited Q(sub 1) and Q(sub 2) states, which define the core orbitals. The fast atom energy distribution peaks at 4 eV.
The implications of processing event sequences for theories of analogical reasoning

Sternberg (1977a, 1977b) has proposed a componential theory of information processing on analogies. The current study attempts convergent validation of the basic findings in verbal analogies by a method that is based on different underlying assumptions. Although the data were generally consistent with Sternberg’s theory, the data indicated thatapplication is better described by two separate events. Furthermore, the extent of individual differences in strategy models was so substantial that a higher level processing operation, such as control strategies, should be postulated, rather than to support a single-strategy model as characterizing Analogy solving.
Fair Use and Free Inquiry: Copyright Law and The New Media

(1980). Fair Use and Free Inquiry: Copyright Law and The New Media. Performing Arts Review: Vol. 10, No. 4, pp. 459-466.
A comparative study of district and individual energy systems providing electrical-based heating, cooling, and domestic hot water to a low-energy use residential community

Abstract This study analyzes potential benefits of centralized systems providing space conditioning and domestic hot water to a small community of electric-only low-energy use dwellings in Northern California. Benefits are analyzed in terms of levelized cost and site energy use. Two district-based scenarios, served by a central ground source heat pump and a central electric boiler with individual air conditioning units, are compared against a decentralized business as usual scenario with individual electric space heaters, air conditioning units and storage-type electric water heaters. Electricity use and levelized cost were modeled in TRNSYS. For a 3-dwelling system with total thermal energy demand of 14.2 MW h/y and peak load of 12.7 kW, the district ground source heat pump configuration uses less electrical energy and power. However, the business as usual system has the lowest levelized cost due to the high cost of the ground-source heat pump installation. Levelized cost was most sensitive to capital cost and number of dwellings connected to the system for the district configurations considered. A 30% decrease in capital cost of the district system resulted in 21% average decrease of levelized cost, while a 100% increase in the number of dwellings resulted in an average 17% decrease of cost.
Intensity masking to get high-resolution images from low-quality apertures

The effort and expense required to build and maintain an optical-quality telescope increases dramatically with the size of the telescope aperture, and this is especially so in space. But scenarios have been proposed for deploying (for instance, inflatable) telescopes with very large but considerably lecithin optical-quality apertures. Our interest is in ameliorating the effects of the low quality aperture in order to exploit the raw size of the aperture to obtain high resolution images. We describe an algorithm for generating an adaptive binary mask to correct the time-varying aberrations of very large apertures which are many (possibly hundreds of) wavelengths out of figure. The technique is limited to monochromatic imagery, though the wavelength at which observations are taken can be readily changed on the fly, and for earth-pointing applications, the limited light-gathering power imposed by the monochromatic filter is not a problem. The mask itself can be placed at the exit pupil of the telescope, which permits implementation on a large scale. A similar approach, in which the pixels of the mask are half-wave phase shifters instead of opaque optical elements, was described by Love et al.
Differential maintenance and de novo methylating activity by three DNA methyltransferases in aging and immortalized fibroblasts.

Genomic methylation, which influences many cellular processes such as gene expression and chromatin organization, generally declines with cellular senescence although some genes undergo paradoxical hypermethylation during cellular aging and immortalization. To explore potential mechanisms for this process, we analyzed the methylating activity of three DNA methyltransferases (Dnmts) in aging and immortalized WI-38 fibroblasts. Overall maintenance methylating activity by the Dnmts greatly decreased during cellular senescence. In immortalized WI-38 cells, maintenance methylating activity was similar to that of normal young cells. Combined de novo methylation activity of the Dnmts initially decreased but later increased as WI-38 cells aged and was strikingly elevated in immortalized cells. To further elucidate the mechanisms for changes in DNA methylation in aging and immortalized cells, the individual Dnmts were separated and individually assessed for maintenance and de novo methylating activity. We resolved three Dnmt fractions, one of which was the major maintenance methyltransferase, Dnmt1, which declined steadily in activity with cellular senescence and immortalization. However, a more basic Dnmt, which has significant de novo methylating activity, increased markedly in activity in aging and immortalized cells. We have identified this methyltransferase as Dnmt3b which has an important role in neoplastic transformation but its role in cellular senescence and immortalization has not previously been reported. An acidic Dnmt we isolated also had increased de novo methylating activity in senescent and immortalized WI-38 cells. These studies indicate that reduced genome-wide methylation in aging cells may be attributed to attenuated Dnmt1 activity but that regional or gene-localized hypermethylation in aging and immortalized cells may be linked to increased de novo methylation by Dnmts other than the maintenance methyltransferase.
A Fuzzy Approach to Natural Resource Management from a Regional Perspective

Abstract This paper describes an approach to regional natural resource management that explicitly incorporates both the uncertainty and the multi-objective nature of such large-scale systems. A fuzzy linear programming algorithm is used to analyze sets of land management alternatives designed for individual forests within a region. Fuzziness is introduced in recognition that regional goal aspiration levels, interactions among resources, and cost estimates are imprecise and uncertain. An illustrative example, based on the 1989 RPA National Assessment Resource Interactions Model of the USDA Forest Service, is applied to the California Region and is used to test various fuzzy modelling approaches. Results show that: (a) regional optimization produces significant cost savings when compared with the solution obtained by aggregating individually optimized forest plans for the region, and (b) fuzzy-based regional solutions may offer decision makers a wider range of preferable solutions than those based solely on linear programming.
Stress relaxation behavior of corn distillers dried grains with solubles (DDGS) in relation to caking

Abstract Interaction of DDGS with the environment causes logistical challenges during handling and transportation, and leads to final product quality loss which is currently a major hurdle in marketing DDGS. Understanding the caking behavior of DDGS is one of the major unsolved problems that impacts the logistics and marketability of DDGS. Moisture content, temperature, compression force and time of consolidation influence the mechanical properties of powder materials by stimulating stickiness and eventual caking of bulk powders. The effect of these variables on stress relaxation behavior of DDGS was studied. The bulk density of DDGS increased in the range of 40–50% by compression which indicated the reduction in interparticle distance that would cause potential flow problems due to compression. The solidity values decreased with increase in moisture content implying higher cohesion between the DDGS particles. The relatively high asymptotic residual modulus for low moisture content samples indicated the recoverable compressive work and the degree of elasticity which aids to make the bulk solid flow. The results from this study show that dry ( 13%) DDGS which is cohesive.
Healthcare training expenditures in the US between 1982 and 1997: what do they mean for today's organisations?

This paper examines the nature of employer training budgets specifically in the healthcare industry within the general context of industrial training expenditures in the USA. Investigating the period between 1982 and 1997, the inquiry finds that the behaviour of the healthcare industry is atypical. Thus, while the findings, consistent with other studies, are that industries for the most part have been growing their training budgets, the same cannot be said for organisations that deliver health services. These findings suggest that industries' willingness to invest in their workforce may vary and have a potentially significant impact on how they serve the larger society.
Effectiveness of androgen deprivation therapy in prolonging survival of older men treated for locoregional prostate cancer.

Epidemiologic and experimental evidence suggests the effectiveness of androgen deprivation therapy (ADT) in prostate cancer (CaP) management. Although ADT has been increasingly used as mono-therapy in CaP, the survival benefit of ADT remains unclear. We examined the effectiveness of ADT in prolonging survival in a community-based cohort of 64 475 older men diagnosed with locoregional CaP, in 1992–1999 with last follow-up through December 2002, in 11 Surveillance Epidemiology and End Results (SEER) registries. The effect of ADT on survival was assessed using Kaplan–Meier's method, log-rank test and Cox proportional hazards. After adjustment for propensity to receive ADT, the ADT and non-ADT groups were significantly different in the distribution of covariates except for comorbidity score and SEER registries. The crude overall mortality was significantly higher in cases with ADT compared with cases that received no ADT, hazard ratio (HR=1.54; 95% CI=1.50–1.58). However, mortality was substantially reduced (1.04, 1.00–1.08) after adjusting for standard care, socio-demographics, tumor characteristics, prognostic factors and chemotherapy. Therefore, ADT was not associated with significantly increased survival benefit for older men with locoregional CaP. Further studies may be needed to explore whether ADT is associated with other health benefits and the cost-effectiveness of these benefits.
Long-term therapy with tolmetin in rheumatoid arthritis.

: Data from over 1000 patients with rheumatoid arthritis who received tolmetin sodium in double-blind and open studies have been pooled to assess long-term efficacy and safety. Duration of the studies was 12 weeks to 48 months. Mean age of patients was 54 years; ratio of males to females was 1:3. The results showed that tolmetin provided rapid onset of action and continuous progressive decrease in symptoms in all measurements of inflammation. Mean number of painful joints was reduced from 22 at baseline to 16 at one month, to 9 at one year, and to 6 at two years. Duration of morning stiffness was 155 minutes at baseline, 123 minutes at one month, 74 minutes at one year, and 78 minutes at two years. The final global evaluation by the investigators showed that 61 per cent of patients had a marked or moderate response. Mean erythrocyte sedimentation rates did not increase during therapy with tolmetin. Initial dose of tolmetin in the patients pooled for this analysis was generally 600 to 800 mg/day, and the mean dose throughout the study was 1256 mg/day. The drug was well tolerated overall. As anticipated, gastrointestinal symptoms were the most frequently reported; nausea was experienced by 13 per cent of the patients at some time during therapy, and gastrointestinal distress, dyspepsia, or abdominal pain was reported by approximately 8.6 per cent each. Only 12.7 per cent of patients discontinued tolmetin because of untoward reactions; 15.9 per cent of patients discontinued because of insufficient therapeutic response. The results of these long-term studies of patients with rheumatoid arthritis demonstrated that tolmetin is an effective antiinflammatory agent with an acceptable record of safety.
Axiomatic analysis of non-transitivity of preference and of indifference

This paper analyzes the usual Bayesian (money pump) argument for transitivity of preference and of indifference: that violation of transitivity is incoherent, since it requires an appreciable payment of money, with no benefit inreturn. The analysis shows that this argument is invalid, because the payment may be negligible. The analysis also shows that not only does non-transitivity require interminable trading (which is incoherent, because it wastes valuable time) but so does transitive indifference. This paradox motivates three axiomatic theories. With suitable axioms that uncover hidden assumptions, the first theory confirms the validity of the previous intuitive analysis. A technical modification of the axioms then replaces the first theory with the more reasonable second theory. The latter proves that trading is terminated under two of the three kinds of violation of transitivity, but remains interminable under cyclic preference. The third theory complements the second theory by studying a single free choice with neither trading nor money payments. It proves that cyclic preference is indecisive, while the other two violations of transitivity are decisive. Therefore, the axiom of transitivity is not a necessary truth for a general prescriptive decision theory, because it can be violated coherently. If a decision maker insists upon doing this, however, then he is simply unable to solve his decision problem under uncertainty by means of Bayesian decision theory.
Effects of viloxazine with and without alcohol on performance tests related to driving in normal volunteers

The effects of single doses of 50 mg of viloxazine, 100 mg of viloxazine, 50 mg of imipramine, and placebo given alone and in combination with alcohol on perceptual-motor performance potentially related to driving were studied in eight normal subjects. The study design permitted testing of visual reaction time, pursuit rotor performance, and depth perception when blood levels of the active drugs and alcohol were at or near peak. Analyses revealed that the effects of alcohol increased visual reaction time and decreased pursuit rotor performance. None of the drugs produced statistically significant changes on any of the measures. None of the effects of the combined drug and alcohol conditions differed significantly from the effects of alcohol alone.
Protein Kinase Cɛ (PKCɛ) and Src Control PKCδ Activation Loop Phosphorylation in Cardiomyocytes

Protein kinase Cdelta (PKCdelta) is unusual among AGC kinases in that it does not require activation loop (Thr(505)) phosphorylation for catalytic competence. Nevertheless, Thr(505) phosphorylation has been implicated as a mechanism that influences PKCdelta activity. This study examines the controls of PKCdelta-Thr(505) phosphorylation in cardiomyocytes. We implicate phosphoinositide-dependent kinase-1 and PKCdelta autophosphorylation in the "priming" maturational PKCdelta-Thr(505) phosphorylation that accompanies de novo enzyme synthesis. In contrast, we show that PKCdelta-Thr(505) phosphorylation dynamically increases in cardiomyocytes treated with phorbol 12-myristate 13-acetate or the alpha(1)-adrenergic receptor agonist norepinephrine via a mechanism that requires novel PKC isoform activity and not phosphoinositide-dependent kinase-1. We used a PKCepsilon overexpression strategy as an initial approach to discriminate two possible novel PKC mechanisms, namely PKCdelta-Thr(505) autophosphorylation and PKCdelta-Thr(505) phosphorylation in trans by PKCepsilon. Our studies show that adenovirus-mediated PKCepsilon overexpression leads to an increase in PKCdelta-Thr(505) phosphorylation. However, this cannot be attributed to an effect of PKCepsilon to function as a direct PKCdelta-Thr(505) kinase, since the PKCepsilon-dependent increase in PKCdelta-Thr(505) phosphorylation is accompanied by (and dependent upon) increased PKCdelta phosphorylation at Tyr(311) and Tyr(332). Further studies implicate Src in this mechanism, showing that 1) PKCepsilon overexpression increases PKCdelta-Thr(505) phosphorylation in cardiomyocytes and Src(+) cells but not in SYF cells (that lack Src, Yes, and Fyn and exhibit a defect in PKCdelta-Tyr(311)/Tyr(332) phosphorylation), and 2) in vitro PKCdelta-Thr(505) autophosphorylation is augmented in assays performed with Src (which promotes PKCdelta-Tyr(311)/Tyr(332) phosphorylation). Collectively, these results identify a novel PKCdelta-Thr(505) autophosphorylation mechanism that is triggered by PKCepsilon overexpression and involves Src-dependent PKCdelta-Tyr(311)/Tyr(332) phosphorylation.
High rate reversibility anode materials of lithium batteries from vapor-grown carbon nanofibers.

We demonstrate the high-rate capability of lithium ion insertion−deinsertion reactions in carbon nanofibers (CNFs). The morphology of CNFs with structural and surface defects, due to the mixed features of disordered and graphitic carbon, plays an important role in both the enhancement of the lithium ion storage and the rate-determining reactions during the topotactic process. The reversible specific capacity of the CNFs at a 0.1 C rate was 461 mA·h/g. The most promising property, which is expected to overcome the hurdles of lithium batteries for high-power applications, is that they deliver considerably high specific capacity even at a very high charge−discharge current, i.e., at a cycling rate of 10 C the reversible capacity is around 170 mA·h/g with a 95% Coulombic efficiency.
Ultrafiltrable calcium and the conformation of albumin

Abstract As a function of pH, the binding of calcium to human serum albumin is correlated with the conformation of the protein. On addition of base at pH 7–8, it appears that calcium binding increases as carboxyl groups of the albumin molecules are unmasked by structural transformation.
Influence of the Fight BAC! Food Safety Campaign on an Urban Latino Population in Connecticut

Abstract Objective To assess the coverage and consumer satisfaction with the Fight BAC! campaign and to evaluate the influence of the campaign on food safety knowledge, attitudes, and behaviors among a predominantly Latino population living in inner-city Hartford, Connecticut. Design A cross-sectional pre- and postsurvey was administered to 500 Latino consumers in either English or Spanish. It included 30 food safety-related questions and information on the socioeconomic and demographic characteristics of participants. Setting and Participants Respondents were selected from Latino households, with at least one child 12 years old or under, located in 5 predominantly Latino neighborhoods in inner-city Hartford. Intervention Fight BAC! media campaign. Results Seventy-three percent of respondents were exposed to at least one campaign media item and were highly satisfied with it. Recognition of the Fight BAC! logo increased from 10% to 42% between surveys ( P P P = .01). There was a dose-response association between the degree of campaign exposure and awareness of the term "cross-contamination." Conclusion and Implications Social marketing campaigns that take advantage of multiple culturally relevant media channels are likely to improve food safety awareness and bring about changes in food safety knowledge and attitudes among Latino consumers.
Active Optics With Room Temperature Vulcanizing Silicone Rubber

A novel method of constructing variable focal length lens employing clear two component room temperature vulcanizing (RTV) silicone rubber is presented. Deformation of the lens is achieved by symmetrically applying pressure through a fluid to a slab of RTV-rubber in such a manner as to change the shape with minimum optical distortion. The theory of deformation of a flexible slab is presented and the optical manifestations predicted. Two different configurations of the variable focal length lens were constructed and experiments performed to measure refraction as well as surface properties. It is found that to first order the theory and experiment agree well. With this theoretical tool expanded to higher orders, new and interesting optical designs should be possible using RTV-rubber lens.© (1977) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Development of an effective treatment program for childhood acute lymphocytic leukemia: A preliminary report†

The development of an effective therapeutic regimen for acute lymphocytic leukemia (ALL) of childhood is described. By careful surveillance of toxicity and efficacy, positive modifications of treatment strategy were achieved without resorting to classically randomized trails. Teh resultant protocol utilizes vincristine-prednisone induction followed by asparaginase consolidation, intensive intermittent combination maintenance chemotherapy with adriamycin as a major component, and cranial radiotherapy plus intrathecal methotrexate for central nervous system prophylaxis. Preliminary analysis suggests that this regimen may result in prolonged continuous complete remission in at least 80% of children with ALL.
On the effective implementation of a boundary element code on graphics processing units using an out-of-core LU algorithm☆

Abstract A collocation boundary element code for solving the three-dimensional Laplace equation, publicly available from http://intetec.org , has been adapted to run on an Nvidia Tesla general-purpose graphics processing unit (GPU). Global matrix assembly and LU factorization of the resulting dense matrix are performed on the GPU. Out-of-core techniques are used to solve problems larger than the available GPU memory. The code achieved about 10 times speedup in matrix assembly over a single CPU core and about 56 Gflops/s in the LU factorization using only 512 Mbytes of GPU memory. Details of the GPU implementation and comparisons with the standard sequential algorithm are included to illustrate the performance of the GPU code.
Whirling and stability of flywheel systems, part II: Comparison of numerical results obtained with combined and lumped parameter models

Abstract In this paper the theoretical analyses of Part I are applied to some flywheel systems to provide information to designers. The analyses are utilized to study three specific prototype flywheel systems: a multi-material ring type (Garrett AiResearch), a constant-thickness-disk ring type (General Electric), and a tapered-thickness-disk type (Lawrence Livermore National Laboratory). In addition, the effects of the following flywheel design parameters on system dynamics are investigated: flywheel mass, flywheel diametral and polar mass moments of inertia, location of flywheel diametral and polar mass moments of inertia, location of flywheel mass center from the lower end of the quill shaft, quill shaft length, lower turbine-bearing support stiffness, and equivalent viscous damping coefficient of the external damper.
Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation after cardiothoracic surgery.

STUDY OBJECTIVE To determine whether prophylactic amiodarone, dosed according to Atrial Fibrillation Suppression Trial (AFIST) I and II regimens, is a cost-effective strategy for prevention of postoperative atrial fibrillation. DESIGN Cost-effectiveness analysis of retrospective cohort study. SETTING Urban, academic hospital. PATIENTS A total of 2046 patients who underwent cardiothoracic surgery between February 1, 1998, and October 31, 2003. Of these patients, 186 received amiodarone and 1860 served as controls. MEASUREMENTS AND MAIN RESULTS Each patient who received prophylactic amiodarone using the AFIST I or II dosing strategies was matched for age, sex, history of valvular surgery, history of atrial fibrillation, beta-blocker intolerance, and receipt of preoperative digoxin therapy with 10 patients who did not receive prophylactic amiodarone. Occurrence of postoperative atrial fibrillation, total hospital costs, and both intensive care unit (ICU) and total hospital length of stay (LOS) were compared between groups. Nonparametric bootstrapping was conducted to examine study results as part of a quadrant analysis and to calculate confidence intervals for the incremental cost-effectiveness ratio. The ICU and total hospital LOS, and total costs for patients with and without postoperative atrial fibrillation were also compared. Fewer patients receiving prophylactic amiodarone developed postoperative atrial fibrillation compared with controls (23.1% vs 29.9%, p=0.05). Total hospital costs for the amiodarone group were 28% less than those for the control group (24,131 US dollars +/- 26,539 vs 33,518 US dollars +/- 40,892, p=0.002). Approximately 98% of the time, patients receiving amiodarone prophylaxis fell into the quadrant that showed superior efficacy and lower total costs. Patients who developed postoperative atrial fibrillation, compared with those who did not, regardless of amiodarone prophylaxis, had a longer mean +/- SD stay in the ICU (6.9 +/- 17.1 vs 3.7 +/- 7.9 days, p<0.001), a longer mean total hospital LOS (14.8 +/- 18.8 vs 10.2 +/- 10.4 days, p+/-0.001), and higher mean total hospital costs (41,574 US dollars +/- 54,721 vs 28,968 US dollars +/- 31,046, p<0.001). CONCLUSION Prophylactic amiodarone was shown to reduce the occurrence of postoperative atrial fibrillation as well as total hospital costs in patients undergoing cardiothoracic surgery. In patients who developed postoperative atrial fibrillation, both ICU and total hospital LOS as well as total hospital costs were increased.
Development of a systematic approach to space qualification of silicon carbide for mirror applications

Over the last few years significant progress has been made in the development of silicon carbide (SiC) for mirror applications. These improvements include lightweighting techniques, higher production yields, and larger diameter apertures. It is now necessary to evaluate and address the systems engineering challenges facing this material to ensure space qualification and integration into future space applications. This paper highlights systems engineering challenges, suggests areas of future development, and proposes a systematic path forward that will outline necessary steps to space qualify this new material.
Comparison of (R)‐[3H] Tomoxetine and (R/S)‐[3H] Nisoxetine Binding in Rat Brain

(R)-[ 3 H]Tomoxetine is a radioligand that binds to the norepinephrine (NE) uptake site with high affinity but also binds to a second, lower-affinity site. The goal of the present study was to identify the nature of this low-affinity site by comparing the binding properties of (R) [ 3 H]tomoxetine with those of (R/S)-[ 3 H] nisoxetine, a highly selective ligand for the NE uptake site. In homogenate binding studies, both radioligands bound to the NE uptake site with high affinity, whereas (R)-[ 3 H]tomoxetine also bound to a second, lower-affinity site. The autoradiographic distribution of binding sites for both radioligands is consistent with the known distribution of NE-containing neurons. However, low levels of (R)-[ 3 H]-tomoxetine binding were seen in the caudate-putamen, globus pallidus, olfactory tubercle, and zona reticulata of the substantia nigra, where (R/S)-[ 3 H] nisoxetine binding was almost absent. In homogenates of the caudate-putamen, the NE uptake inhibitors desipramine and (R)-nisoxetine and the serotonin (5-HT) uptake inhibitor citalopram produced biphasic displacement curves. Autoradiographic studies using 10 nM (R)-nisoxetine to mask the binding of (R)-[ 3 H]tomoxetine to the NE uptake site produced autoradiograms that were similar to those produced by [ 3 H] citalopram. Therefore, (R)-[ 3 H]tomoxetine binds to the NE uptake site with high affinity and the 5- HT uptake site with somewhat lower affinity