cssi/SciSciGPT-SciSciNet huggingface dataset:
Dollars and democracy in Hong Kong: Understanding the logic of Chinese policy

Recent disputes between China and Great Britain over political reform and airport financing in Hong Kong have helped clarify the logic of Chinese policy toward the territory. Despite appearances to the contrary, the disputes are only partly about democracy and money. For the PRC, they are fundamentally about creating the conditions for the Chinese government to exercise sovereignty after 1997 and about the fear that Great Britain will do anything possible to complicate China’s establishment of authority over the territory. This article thus rejects as inadequate several conventional explanations for China’s Hong Kong policy. Its conclusions hold significant implications for Hong Kong’s future and for our understanding of China’s foreign policy calculations elsewhere.
Establishing assessment indexes for emergency response capability of disease control and prevention institutions

Objective To establish an emergency response capability assessment indexes for disease control and prevention institutions. Methods Health emergency response capability assessment indexes of Shanghai Centers for Disease Control and Prevention(CDCs) was drafted based upon documentary analysis, expert consultation and focus group discussion according to duties and features of emergency work of CDCs. The assessment indexes were determined by applying Delphi method (18 experts), and the weights of indexes were determined using analytic hierarchy process and proportional distribution method. And then the established index system was used to assess the emergency response capability of CDCs in Shanghai. Results Two rounds of expert consultations were conducted. Kendall's coefficient of concordance was 0.420 and 0.495 at the first and second round of expert consultations respectively. After two rounds of consultations, the expert authority score was above 0.7. There were 7 primary indexes, 24 secondary indexes and 84 third-level indexes. The seven primary indexes included emergency management system, emergency response team, surveillance and early-warning ability, emergency response capacity, emergent supply capability, communication and cooperation, scientific research and exchange, with systematic weights of 0.2123, 0.1754, 0.1334, 0.1916, 0.1281, 0.0962 and 0.0630,respectively. According to the investigation, Shanghai Municipal Center for Disease Control and Prevention ranked first in the total score of emergency response capability evaluation. Conclusions The indexes identified in this study have good reliability and feasibility, and can be used in assessment of emergency response capability in disease prevention and control institutions.
A lever action hypothesis for pendulous hummingbird flowers: experimental evidence from a columbine

BACKGROUND AND AIMS Pendulous flowers (due to a flexible pedicel) are a common, convergent trait of hummingbird-pollinated flowers. However, the role of flexible pedicels remains uncertain despite several functional hypotheses. Here we present and test the 'lever action hypothesis': flexible pedicels allow pendulous flowers to move upwards from all sides, pushing the stigma and anthers against the underside of the feeding hummingbird regardless of which nectary is being visited. METHODS To test whether this lever action increased pollination success, we wired emasculated flowers of serpentine columbine, Aquilegia eximia, to prevent levering and compared pollination success of immobilized flowers with emasculated unwired and wire controls. KEY RESULTS Seed set was significantly lower in wire-immobilized flowers than unwired control and wire control flowers. Video analysis of visits to wire-immobilized and unwired flowers demonstrated that birds contacted the stigmas and anthers of immobilized flowers less often than those of flowers with flexible pedicels. CONCLUSIONS We conclude that flexible pedicels permit the levering of reproductive structures onto a hovering bird. Hummingbirds, as uniquely large, hovering pollinators, differ from flies or bees which are too small to cause levering of flowers while hovering. Thus, flexible pedicels may be an adaptation to hummingbird pollination, in particular due to hummingbird size. We further speculate that this mechanism is effective only in radially symmetric flowers; in contrast, zygomorphic hummingbird-pollinated flowers are usually more or less horizontally oriented rather than having pendulous flowers and flexible pedicels.
THE EFFECT OF SOLVENT AND TEMPERATURE VARIATION ON THE VIBRATION FREQUENCY OF THE CARBONYL AND NITRILE BONDS

Summary * A series of solvents of varying polarizabilities and permanent dipole moments were used to prepare dilute solutions of acetonitrile, acetone and phenyl nitrile. The frequencies of the C = 0 and C = N stretching vibrations were then measured over a range of temperatures from below the freezing point to the boiling point of each solvent, utilizing a variable temperature infrared cell of our design. In most cases the frequencies shifted toward the red as the temperature was lowered, the frequency shift depending qualitatively on the polarizability and dipole moment of the solvent, but not in quantitative agreement with existing theories. A comparison with the familiar Kirkwood-Bauer-Magat and Buckingham formulae will be made. In the case of phenyl nitrile in solvents consisting of large molecules with permanent dipoles (e.g., nitrobenzene or toluene) the frequency shift was slightly towards the blue with decreasing temperature. To our knowledge, this is the first example of a reversed frequency shift with temperature which has been reported. A possible explanation for this phenomenon is that the overall dipole moment of the phenyl nitrile molecule is opposite in direction to the moment of the C = N bond, thus as the molecule assumes its lowest energy orientation with respect to neighboring dipoles, the nitrile group is held in a high energy state electrostatically and the vibration is somewhat perturbed toward higher frequencies. This hypothesis is being tested by further experiments.
Towards Better Management of Combined Sewage Systems

In New York and New Jersey, and many older areas in the United States, stormwater runoff is cleared from the streets and is dispensed into combined sewers. These combined sewers transport both runoff and domestic waste through pipes that lead to wastewater treatment plants. The problem is that when it rains a couple of tenths of an inch, the runoff enters the sewer and dramatically increases the amount of water and domestic waste in the sewer, exceeding the maximum capacity. This causes the water-waste mixture to bypass the treatment plant and dispense into the nearest waterway (e.g. the Hudson River). This pollutes the waterway it enters and makes the environment uninhabitable for wildlife it used to support, and unsafe for the people that use it. The introduction of rain barrels - barrels that collect stormwater runoff from the roofs of buildings - can delay the runofffrom going into the sewer, allowing it to be dispensed in a manner that the sewer systems can manage. [1]
Abstract P533: Food Shopping Practices of Low-income African American Women: Associations With Features of the Food Environment

Introduction: The food environment has received considerable attention as a potential correlate of diet-related CV health. Features of the food environment are assumed to influence the places where...
Trade-Offs in Quality-of-Life Assessment Between the Modified Rankin Scale and Neuro-QoL Measures

Abstract Introduction We aimed to describe the physical and cognitive health of patients with differing levels of post-stroke disability, as defined by modified Rankin Scale (mRS) scores. We also compared cross-sectional correlations between the mRS and the Quality of Life in Neurological Disorders (Neuro-QoL) T-scores to longitudinal correlations of change estimates from each measure. Methods Mean Neuro-QoL T-scores representing mobility, dexterity, executive function, and cognitive concerns were compared among mRS subgroups. Fixed-effects regression models with robust standard errors estimated correlations among mRS and Neuro-QoL domain scores and correlations among longitudinal change estimates. These change estimates were then compared to distribution-based estimates of minimal clinically important differences. Results Seven hundred forty-five patients with ischemic stroke (79%) or transient ischemic attack (21%) were enrolled in this longitudinal observational study of post-stroke outcomes. Larger differences in cognitive function were observed in the severe mRS groups (ie, 4-5) while larger differences in physical function were observed in the mild-moderate mRS groups (ie, 0-2). Cross-sectional correlations among mRS and Neuro-QoL T-scores were high (r = 0.61-0.83), but correlations among longitudinal change estimates were weak (r = 0.14-0.44). Conclusions Findings from this study undermine the validity and utility of the mRS as an outcome measure in longitudinal studies in ischemic stroke patients. Nevertheless, strong correlations indicate that the mRS score, obtained with a single interview, is efficient at capturing important differences in patient-reported quality of life, and is useful for identifying meaningful cross-sectional differences among clinical subgroups.
Experimentally Verified Alcohol Adsorption Isotherms in Nanoporous Materials from Literature Meta-Analysis

Systematic collection of replicate experimental data via literature meta-analysis is a powerful approach for assessing the reproducibility of physical properties data. In this paper, we use meta-an...
Toward Stable, General Machine-Learned Models of the Atmospheric Chemical System

Atmospheric chemistry models—used as components in models that simulate air pollution and climate change—are computationally expensive. Previous studies have shown that machine-learned atmospheric chemical solvers can be orders of magnitude faster than traditional integration methods but tend to suffer from numerical instability. Here, we present a modeling framework that reduces error accumulation compared to previous work while maintaining computational efficiency. Our approach is novel in that it: 1) uses a recurrent training regime that results in extended (>1 week) simulations without runaway error accumulation, and 2) can reversibly compress the number of modeled chemical species by >80% without further decreasing accuracy. We observe a ~260× reduction in computation time (~1900× when run on specialized hardware) compared to the traditional solver. We use random initial conditions in training to promote general applicability across a wide range of atmospheric conditions. For ozone (with an initial concentration range of 0–70 ppb), our model predictions over a 24-hour simulation period match those of the traditional solvers with median error of 2.7 ppb and less than 19 ppb error across 99% of simulations initialized with random noise. Error can be significantly higher in the remaining 1% of simulations, which include among the most extreme concentration fluctuations simulated by the reference model. Results are similar for total particulate matter (median error of 16 ug/m3 and <32 ug/m3 across 99% of simulations with concentrations ranging from 0-150 ug/m3). Finally, we discuss practical implications of our choice of modeling framework and next steps for improving performance. The machine learning models described here are not yet suitable replacements for traditional chemistry solvers but represent a step toward that goal.
Big Fish, Small Pond: How In-Charge Auditors Engage with Technology-Based Audit Tools to Influence the Audit in Non-Global Network Firms

I investigate how in-charge auditors emerge as big fish within the smaller ponds of non-global network firms (NGNFs) (i.e., firms other than the “Global 7”) to engage in institutional work using technology-based audit tools (TBATs) to impact audit quality. Using semi-structured interviews through the lens of institutional theory, I identify factors associated with in-charges’ propensity to engage in institutional work, being actions that contribute to the development (i.e., creation), continuance (i.e., maintenance), and/or breach (i.e., disruption) of practice. Findings identify audit firm culture, engagement budgets, and training experiences as important antecedents to individuals’ ability to pursue institutional work and effect change. Evidence suggests auditors internalize the time-relevance of their actions differently, and these perspectives are predictive of the nature of the institutional work auditors pursue. Data also give rise to new process-theory research questions regarding audit firms’ technological cultures, trainings, auditor-client interactions, and ceremonial practices as promising research avenues.
The Stem Education Management and the Learning in the 21st Century of Secondary School Students in Thailand

The research of the STEM Education Management and the Learning in the 21st Century of secondary school students in Thailand has the purpose of studying the levels of success in STEM Education Management of the secondary schools. To study the levels of Learning in the 21st Century of secondary school students and to study the correlation between the levels of the Success of STEM Education Management and the levels of Learning in the 21st Century of secondary school students in Thailand. The sample group consisted of 361 students in secondary schools where there is the learning system of STEM Education, in the Bangkok area and the vicinity. Tools used are questionnaires, statistic is by mean, pearson’s simple correlation moment. It is found that the level of the Success in STEM Education Management of secondary schools, overall, is at a moderate level. The level of Learning in the 21st Century of secondary school students, overall, is at a moderate level. It is also found that the level of the Success in STEM Education Management of the schools and the level of Learning in the 21st Century of secondary school students, overall, has a correlation at a moderate level with statistic significant at .01 and coefficient correlation of .699.
Changes in retail sales of tobacco products in Ontario after a menthol sales restriction.

Background Ontario, Canada prohibited menthol tobacco product sales beginning 1 January 2017. We measured retail sales of menthol cigarettes and possible substitute products before and after policy implementation in Ontario. Methods We licensed retail scanner data for tobacco product sales in Ontario and British Columbia (BC), a comparison province without a menthol tobacco policy at that time. We assessed changes in per capita unit sales (per 1000 people) from pre-policy (January–June 2016) to post-policy (January–June 2017) periods. Classification of cigarettes as menthol or non-menthol, or having menthol-suggestive descriptors (‘green’, ‘blue’, ‘silver’ and ‘fresh’), was based on scanner data. Results Ontario menthol cigarette sales decreased 93%, from 596 to 40 packs per capita compared with a 2% decrease (696 to 679 packs per capita) in BC. Menthol capsule cigarette sales remained low in Ontario ( 99%) pre-policy sales of cigarettes with ‘green’ menthol-suggestive descriptors were menthol cigarettes, but post-policy, 94% of ‘green’ cigarettes sold were non-menthol. Conclusions Ontario’s menthol policy was associated with a decrease in retail sales of cigarettes classified as menthol, with little evidence of product substitution. Understanding changes in sales of cigarettes with menthol-suggestive descriptors would be informative.
Field emitter array patterning for large scale flat panel displays using laser interference lithography

Summary form only given. We present our research on interference lithography for field emission flat panel display applications. We report on a laser interference lithography technique that is capable of exposing very high density (/spl ges/10/sup 9/ dots/cm/sup 2/) sub-quarter micron patterns over very large fields (/spl ges/10/sup 4/) with excellent uniformity.
True Urbanism: Living In and Near the Center

With his book's title, Hinshaw establishes his intent to describe what for him is the authentic and preferred expression of the American urban experience. Supported by examples of what has been don...
A DYNAMIC MODEL OF AN ENVIRONMENTAL SYSTEM WITH n INTERACTING COMPONENTS AND p DEGREES OF FREEDOM

The nonlinear differential equations of growth proposed by Volterra (1931) are used as the basis for a dynamic model of ann-element system withp specified, terminal conditions andp missing initial conditions. The resulting two-point boundary-value problem can be solved, ifp is not large, by the shooting method used previously by Huddleston (1967). A numerical example withn=4 andp=2 is solved on a digital computer, and some results are presented.
A new field‐aligned current index AF and its relation to the storm‐time ring current and energetic neutral atom (ENA) emissions

[1] It is shown that a newly devised field-aligned current index AF is well correlated with the Dst index, the correlation coefficient being 0.93. The AF index is based on the fact that geomagnetic Y (or D) component variations in the middle and low latitudes are mainly caused by field-aligned currents. It is also demonstrated that energetic neutral atom (ENA) emissions measured by the Geotail satellite are well correlated with the AF index. INDEX TERMS: 2778 Magnetospheric Physics: Ring Current; 2716 Magnetospheric Physics: Energetic particles precipitating; 2708 Magnetospheric Physics: Current Systems (2409); 2788 Magnetospheric Physics: Storms and Substorms; 2736 Magnetospheric Physics: Magnetosphere/ionosphere interactions
Grid-Enabled Treatment Planning for Proton Therapy Using Monte Carlo Simulations

Grid computing is an emerging technology that enables computational tasks to be accomplished in a collaborative approach by using a distributed network of computers. The grid approach is especially...
Organizational Structure and the Optimal Design of Policymaking Panels: Evidence from Consensus Group Commissions’ Revenue Forecasts in the American States

Increasing both the size and diversity of policymaking panels is widely thought to enhance the accuracy of collective policy decisions. This study advances the theoretical conditions in which improving collective accuracy necessitates an efficient trade-off between a panel's size and its level of organizational diversity. This substitution effect between these organizational characteristics is empirically supported with data on official general-fund revenue forecasts made by consensus group (CG) independent commissions in the American states. Evidence of an asymmetric substitution effect is also uncovered, whereby increasing organizational diversity in large CG commissions produces revenue forecasts that reduce collective accuracy by slightly more than three times as much compared to decreasing such diversity in small CG commissions. This study underscores the limits of organizational diversity as a mechanism for improving collective judgments when policymaking authority is diffuse among many panel members.
Thermal Disturbances in Near Critical Fluids

Previous research into the piston effect used only the van der Waals equation of state for numerical simulation of the piston effect at conditions very close to the critical point. The real gas equation of state is used to compare the pressure and temperature response of oxygen and hydrogen at the critical pressure contained between two infinite parallel plates due to a thermal disturbance at one boundary. The plates were fixed with a separation distance of 2.5 mm. The bulk fluid was initialized to various temperatures ranging from 0.50 to 0.95 times the critical temperature, and then one plate would undergo a step change to 1 K above the critical temperature. The pressure rise in hydrogen after five acoustic time periods was only 17% of the pressure rise in oxygen. The temperature increase in hydrogen was only 30% of the temperature rise in oxygen. On the diffusion timescale, the pressure rise in the oxygen is an order of magnitude larger than the pressure rise in hydrogen for the same thermal penetration depth. The temperature rise in oxygen is four times greater than the temperature rise in hydrogen
Efficient retrieval from sparse associative memory

Abstract Best-match retrieval of data from memory which is sparse in feature space is a time-consuming process for sequential machines. Previous work on this problem has shown that a connectionist network used as a hashing function can allow faster-than-linear probabilistic retrieval from such memory when presented with probing feature vectors which are noisy or partially specified. This paper introduces two simple modifications to the basic Connectionist-Hashed Associative Memory which together can improve the retrieval efficiency by an order of magnitude or more. Theoretical results are presented for storage/retrieval of memory items represented by feature vectors made up of 1000 randomly selected bivalent components. Experimental results on correlated feature vectors are presented in the context of a spelling correction application.
Irreversible processes in isotropic materials with finite deformations

A consistent application of thermodynamics of irreversible processes is presented for Isotropic materials with memory undergoing finite deformations. Explicit expressions for the functional relation between the momentary stresses and temperature and the deformation and internal energy time histories are derived for the special case of internal processes which can be described by even internal scalar variables. The treatment provides a special model for finite and infinitesimal linear viscoelasticity and is compared with existing theories.
Physical configuration and performance modeling of all-dielectric metamaterials

In this paper, physical concept and performance analysis of all-dielectric metamaterials are presented. Metamaterials with desired material parameters $(\ifmmode\pm\else\textpm\fi{}\ensuremath{\epsilon},\ifmmode\pm\else\textpm\fi{}\ensuremath{\mu})$ are developed by creating electric and magnetic resonant modes. Dielectric disk and spherical particle resonators are considered as the great candidates for establishing the dipole moments (metamaterial alphabet). A full wave finite difference time domain technique is applied to comprehensively obtain the physical insights of dielectric resonators. Near-field patterns are plotted to illustrate the development of electric and magnetic dipole fields. Geometric-polarization control of the dipole moments allows $\ensuremath{\epsilon}$ and $\ensuremath{\mu}$ to be tailored to the application of interest. All-dielectric double negative metamaterials are designed. Engineering concerns, such as loss reduction and bandwidth enhancement are investigated.
Isolation and characterization of the digestive proteinases in the earthworm Lumbricus terrestris Linnaeus.

1. 1. Digestive organ homogenates and intestinal fluid from Lumbricus demonstrated strong activity on the synthetic substrates TAME and BAPA; a pH optimum at 8.35–8.45 was found for both substrates. The TAME components were found to be stable at pH 4.5–8.0. 2. 2. The TAME and BAPA activities were inhibited by ovumucoid and DFP, suggesting the presence of a tryptic-like serine proteinase. 3. 3. The crude extracts demonstrated strong carboxypeptidase-A activity on the synthetic substrate HPLA, with pH optima at 5.2 and 7.7. The carboxypeptidase-A activity was inhibited 30 per cent with EDTA and 1,10-phenanthroline. Crude extracts demonstrated activity on Bz-GL, with a pH optimum at 7.7–8.0. 4. 4. No enzymatic activity occurred with the synthetic substrates l-leucinamide and GPANA. 5. 5. Thirteen protein components were separated by acrylamide gel electrophoresis of which five demonstrated caseinase activity. 6. 6. The first and second isolated proteolytic components did not hydrolyze any of the synthetic substrates tested. 7. 7. Proteolytic components 3 and 5 hydrolyzed HPLA. Component 3 demonstrated pH optima of 5.2 and 7.7, while component 5 had a pH optimum of 7.7 only. 8. 8. Proteolytic component 4 hydrolyzed TAME and BAPA. Component 4 also hydrolyzed Bz-GL, the amino side of the basic amino acid. 9. 9. A sixth component hydrolyzed Bz-GL, but caseinase activity was not apparent.
Empirical methods for evaluating dialog systems

We examine what purpose a dialog metric serves and then propose empirical methods for evaluating systems that meet that purpose. The methods include a protocol for conducting a wizard-of-oz experiment and a basic set of descriptive statistics for substantiating performance claims using the data collected from the experiment as an ideal benchmark or "gold standard" for making comparative judgments. The methods also provide a practical means of optimizing the system through component analysis and cost valuation.
Echocardiographic and pathologic features of explanted Hancock and Carpentier-Edwards bioprosthetic valves in the mitral position

Modes of failure of Hancock and Carpentier-Edwards (C-E) porcine bioprosthetic valves placed in the mitral position are not completely understood. We reviewed transesophageal echocardiographic (n = 19) and pathologic features of failed Hancock (n = 22) and C-E (n = 8) porcine mitral valves in 30 patients (mean age 70 +/- 13 years). Age at implantation (59 +/- 14 vs 58 +/-14 years, p = 0.9), time to implanted valve degeneration (13 +/- 5 vs 11 +/- 2 years, p = 0.3), and size of bioprosthesis (30 +/- 2 vs 31 +/- 2 mm, p = 0.14) of the implanted Hancock and C-E valves were similar. Anterior leaflet was flail in 15 versus flail posterior leaflet in 5 patients (p = 0.0004). Eccentric posterior mitral regurgitation jet was present in 12, eccentric anterior jet in 2, central jet in 2, and paravalvular jet in 3 patients. Stenosis of bioprosthesis was present in 1 1 Hancock versus 1 C-E valve (p = 0.06). Stent creep at any stent post was present in 14 Hancock versus no C-E valve (p = 0.0013). Large commissural dehiscence was present in 5 C-E versus 1 Hancock valve (p = 0.0006). Ring margin perforation was the most common perforation in Hancock valves (p <0.05, analysis of variance versus all other Hancock perforations). Dehiscence at the stent posts was the most common perforation in C-E valves (p <0.05 vs other C-E perforations, analysis of variance and p <0.001 versus Hancock valves). Thus, Hancock valves showed greater stenosis and stent creep, whereas C-E valves showed large dehiscences at the stent posts on explantation. The anterior leaflet degenerated most frequently in both valves. These findings suggest that the valve design may influence the mechanisms of porcine valve degeneration.
Determination of the dissociation kinetics of a transient intermediate

Tandem mass spectrometry provides information on the dissociation pathways of gas-phase ions by providing a link between product ions and parent ions. However, there exists a distinct possibility that a parent ion does not dissociate directly to the observed product ion, but that the reaction proceeds through unobserved reaction intermediates. This work describes the discovery and kinetic analysis of an unobserved reaction intermediate with a quadrupole ion trap. [a 4−NH3] ions formed from [YGβFL+H] ions dissociate to [(F*YG−NH3)−CO] ions. It is expected, however, from previous results, that [F*YG−NH3] ions should form prior to [(F*YG−NH3)−CO] ions. Double-resonance experiments are used to demonstrate the existence of intermediate [F*YG − NH3] ions. Various kinetic analyses are then performed using traditional collision-induced dissociation kinetics and double-resonance experiments. The phenomenological rates of formation and decay of peptide rearrangement ion dissociation products are determined by curve fitting decay and formation data generated with the kinetics experiments. The data generated predict an observable level of the intermediate in a time frame accessible but previously not monitored. By examining early product-ion formation, the intermediate ions, [F*YG−NH3]+, are observed.
Aircraft-Electric-Accessory-Vibration Investigations

Flight and laboratory tests are in progress to determine changes in design of aircraft generators which will improve their resistance to vibration-fatigue failure. Vibrations near mountings of generator voltage regulators and reverse-current relays are being measured to provide data for design and testingof these accessories. The paper presents flight vibration data and discusses sources of vibration in aircraft, accessory-vibration characteristics, vibration test apparatus, and investigations of failures of generator mountings and flexible drive asemblies. On the basis of the flight and laboratory tests and other avilable information, recommendations are made for the design of generators which will give most satisfactory mechanical performance. The primary requirements of a generator from the standpoint of avoiding vibration failures are a stiff mounting flange and a flexible drive assembly having a satisfactory damping device.
The impact of airline mergers and hub reorganization on aviation fuel consumption

Abstract In a time of growing aviation cost and competition, airlines are seeking merger partners strategically to reduce cost and boost revenue. A merged airline can eliminate network redundancy by reorganizing and consolidating hub networks and operations resulting in improved fuel efficiency from flow economies of scale. Mergers, however, can have a detrimental impact on customers through decreased service. In this study we investigate the potential of mergers to reduce fuel consumption and balance this against their impact on passengers through service level degradation. We find that across two major US airline mergers in the late 2000s – early 2010s, the number of non-stop destinations and flight frequency per connection dropped significantly while the number of passengers increased considerably. We find the fuel savings achieved by both merged airline networks, ranging from 25 to 28 percent, greatly outweighs the value of passenger service degradation. In projecting these results to predict the potential fuel savings from a merger of the remaining two largest US carriers, we define their future hub structure, consolidation of flows, and find a resulting fuel consumption savings of 23–27 percent.
582. CNS Gene Delivery Targeting CCR3 Protects Brain Microglia from HIV-1

Top of pageAbstract Infection by human immunodeficiency virus (HIV-1) requires virus binding to human CD4 plus a coreceptor. CCR5 and CXCR4, are the primary coreceptors used by most HIV-1 isolates. The eotaxin receptor (CCR3) has also been implicated as a coreceptor for HIV infection, particularly in the microglial cells of the brain. This study focuses on the role of CCR3 in CNS HIV-1 infection and therefore as a target for manipulation gene transfer. Two approaches were applied to targeting CCR3. First an anti- CCR3 hybridoma, 5E8-G9-B4, was used to develop a single chain antibody (SFv) that contained the immunoglobulin variable heavy (VH) and variable light (VL) chain. Using overlapping RT-PCR techniques with hybridoma mRNAs, the two V region coding sequences, separated by a flexible hinge region, were cloned into a mammalian expression vector. We also tested a panel of interfering RNA's designed to target a sequence shared by mouse and human CCR3 transcripts. Both approaches were used to test the effectiveness of CCR3 downregulation and consequent protection from M-tropic strains of HIV-1. Cells were treated by adding soluble siRNAs and by transfecting with an expression construct carrying the SFv cDNA. Transfection efficiencies were measured using a marker gene. Of a panel of CCR3 siRNAs, R3-526, and SFv addition to cultures resulted in 60-80% decrease in CCR3 expression when tested in U87.CD4.CCR3 cells, primary human microglia derived from fetal brain and monocyte derived macrophages (MDM). CCR3 downregulation was measured using FACS and immunostaining. Both the SFv and siRNA also significantly decreased (>70%) productive HIV-1 infection, as measured by p24 HIV infection in microglia cells when tested using two different CCR3-tropic HIV-1 isolates: HIV-1ADA and a primary brain isolate. Strains of HIV-1 that utilize only CCR5 as a coreceptor were not inhibited. Because of their effectiveness in transducing microglial cells, rSV40 vectors carrying these moieties are being prepared. Studies involving transduction of these anti-CCR3 moieties, both to assess their effectiveness in downregulating CCR3 and protecting from CCR3- tropic strains of HIV-1, are in progress. Since CCR3 and CCR5 are expressed by microglial cells, therapies targeting both may be needed in treating CNS AIDS. Utilization of CCR3 by these HIV-1 isolates and their susceptibility to inhibition by anti-CCR3 siRNA and SFv in primary brain microglia/macrophages may both help clarify the role of CCR3 as a coreceptor in CNS establishing HIV-1 and provide useful therapeutic insights.
A physiologically based pharmacokinetic model for retinoic acid and its metabolites

Abstract Background: A physiologically based pharmacokinetic (PBPK) model for all- trans -retinoic acid (tretinoin) was developed to provide a coherent description of tretinoin absorption, distribution, metabolism, and excretion across species and routes of administration. Objective: The goal of developing such a model is to provide a measure of internal dose that would be a biologically relevant surrogate for administered dose in assessing human teratogenic risk from topically applied tretinoin emollient cream. Methods: The developed PBPK model included compartments for plasma, liver, gut, intestinal lumen, fat, skin, richly and slowly perfused tissues, placenta, and embryo. Tretinoin metabolism to 13- cis retinoic acid, oxidation, and glucuronidation were incorporated. Dose surrogates, including the maximum plasma concentration (C max ) and area under the concentration-versus-time curve were calculated from the model. Results: The ability of the model to predict tretinoin pharmacokinetics and to extrapolate across species and routes of administration was tested and validated. Model-derived estimates of dose surrogates demonstrated that the internal exposure to retinoids after topical treatment with 0.05% tretinoin emollient cream is minimal in comparison to that for teratogenic oral doses. The ratio of areas under the curve for total active retinoids after teratogenic oral doses in monkeys versus therapeutic topical doses in human beings, for example, was greater than 450,000 to 1. Conclusion: For topical application of tretinoin in human beings, detoxification via the glucuronidation pathway predominates, resulting in a much lower internal exposure to active retinoids than was inferred from total radioactivity data. The model predicts that topical application of tretinoin results in an internal exposure that is four to six orders of magnitude lower than a minimally teratogenic dose. (J Am Acad Dermatol 1997;36:S77-S85.)
Application of the limit of truncated isotonic regression in optimization subject to isotonic and bounding constraints

An isotonic regression truncated by confining its domain to a union of its level sets is the isotonic regression in the reduced function space. When some of the weights with which the inner product system is defined go to infinity, the truncated isotonic regression converges. This limit can be used in discribing the projection onto the set of vectors which satisfy an order restriction and have one or more of its coordinates bounded above and/or below. Through this characterization, two inequalities associated with the projection are established and found useful in order and bound restricted statistical inference. The results obtained show that for an exponential distribution family the inequalities lead to the linkage of the order and bound restricted MLE with the projection of the unrestricted MLE, and the dominance of the order and bound restricted MLE over the unrestricted MLE with respect to two classes of loss functions and risks as well as Bayes risks.
Studies of Lipase Action. I. Lipase Action in Normal Milk

Summary By a direct determination of the free acids in the fat phase, it has been shown that lipolysis occurs in practically all samples of raw milk, and that there is an appreciable increase in free fatty acids between the time of milking and the time of delivery to a pasteurizing plant. There is only a slight variation in the acidity of the fat in the milk of different cows when it is drawn from the udder, but after a few hours there may be wide variations in the acidity. The rate of lipase action is influenced by the rate of cooling of the milk, being retarded by sufficiently rapid cooling. Milk contains at least two lipases. One is inhibited completely by very small amounts of formalin. The other is apparently not sensitive to moderate amounts of formaldehyde.
Diffusive Coordinate Model for Blinking Suppression and Intensity Fluctuations in CdSe-OPV Quantum Dots

We describe here numerical simulation of a modified Frantsuzov-Marcus diffusive coordinate (DC) model[1] which yields blinking suppression and low frequency fluctuations as observed[2] in Oligo-(phenylene vinylene) (OPV) coated CdSe quantum dots.
Petrographic and chemical characterization of igneous lithic clasts from mesosiderites and howardites and comparison with eucrites and diogenites

Petrographic, electron microprobe, and instrumental neutron activation analysis (INAA) studies of igneous lithic clasts separated from mesosiderites and howardites and INAA investigation of whole rock eucrites and diogenites are presented. The trace element abundances in basaltic lithic clasts indicate more complex differentiation episodes than in eucrites which include sequential melting and expulsion of liquid from the source region and remelting of cumulate materials. Pyroxenites from mesosiderites show slight enrichments in Sc and Mn than diogenites suggesting that these pyroxenites are not fragments of diogenites. It is concluded that the heat source characteristics are spatially and temporally variable, suggesting that heating of the differentiated meteorite parent bodies may have partly come from outside the parent body.
Role of Rac1-GTPase in Glucose Inhibition of Glucagon Secretion

The significance of glucagon in glucose homeostasis is becoming ever clearer, yet the mechanisms underlying its secretion from pancreatic α-cells remain poorly understood. Clinical studies show that drugs that suppress glucagon secretion can restore normoglycemia in diabetic patients, suggesting a possible alternative to insulin treatments. Two classes of models have been proposed to explain glucose inhibition of glucagon secretion (GIGS), but both share a requirement for Ca2+ triggering. In contrast, data from our lab show that changes in α-cell Ca2+ activity do not correlate with GIGS. This suggests that glucagon secretion is suppressed downstream of membrane depolarization, potentially at the level of exocytosis. The F-actin modifying Rac1-GTPase can regulate insulin secretion from β-cells by direct action on the exocytotic machinery. It has been shown that cAMP can regulate Rac1 activation in β-cells through PKA activation. Additionally, glucose metabolism activates the cAMP pathway independently of Ca2+ oscillations, though the complete role of metabolic activity in exocytosis is unknown.Since the α-cell and β-cell are closely related, we hypothesize that GIGS depends on cAMP signaling that leads to deactivation of Rac1 and down-regulation of exocytosis. To identify the role of Rac1 in regulating GIGS, we have developed EGFP-tagged dominant negative and constitutively active Rac1 viral constructs that we use to infect murine islets with RFP-labeled α-cells. This allows us to study directly the effects of Rac1-GTP and Rac1-GDP on α-cell glucagon secretion, Ca2+ activity, and glucose metabolism to determine their relative roles in Rac1-mediated GIGS. Additionally, we are characterizing the glucose dose-response of Rac1 activation in α-cells. Finally, to determine the role of cAMP signaling we are using cAMP and PKA agonists at low and high glucose to identify their effects on Rac1 activation state and glucagon secretion.
Interaction of microwave radiation with turkey sperm.

Turkey sperm were exposed to 2.45 GHz microwave radiation in a temperature controlled waveguide apparatus. Temperature was maintained at 40.0 ± 0.5° C. The sperm were exposed for 30 min to a specific absorption rate (SAR) of 1, 10, or 50 mW/g. Before and following microwave exposure the following parameters were examined: percentage viability, percentage abnormal sperm, and release of the enzymes lactate hydrogenase (LDH) and glutamic oxalic transaminase (GOT). These parameters were not altered significantly by microwave exposure under the conditions tested.
Age, birth cohorts, and drinking: an illustration of the hazards of inferring effects from cohort data.

The ambiguity of many sets of cohort data is illustrated by cohort data on drinking alcoholic beverages from American national surveys conducted during the late 1950s, late 1960s, and late 1970s. Although the data approximate the pattern predicted by pure linear cohort effects, examination of "side information" reveals that they are likely to reflect positive period effects offset from one date to the next by negative age effects. Researchers are cautioned that all available "side information" should be considered before statistical cohort models are tested. Some researchers have tried to use tests of statistical models to answer questions which must be answered before appropriate statistical tests can be applied. Language: en
Thermoregulatory effects of (D-ala2)-methionine-enkephalinamide in the cat. Evidence for multiple naloxone-sensitive opioid receptors.

(D-ala2)-methionine-enkephalinamide (DAME) was injected into the third cerebral ventricle of unrestrained cats. At ambient temperature (Ta)=22°C, 3.1–50 μg caused dose-related hyperthermias. As dosage was increased, the hyperthermias diminished and in some cats hypothermia developed. Hyperthermia was not due to pyrogenic contamination or prostaglandin synthesis since it was not altered by pretreatment with a large IV dose of indomethacin. However, pretreatment with naloxone did cause a dose-related reduction in the hyperthermia. A low dose of DAME (12.5 μg) also caused hyperthermia at Ta=4 and 32°C, indicative of an increase in the level about which body temperature was regulated. On the other hand, a dose of 200 μg, which caused hyperthermia at Ta=22 and 32°C, usually caused hypothermia at Ta=4°C, perhaps due to impairment of thermoregulatory control mechanisms. The response to DAME in the cold was reduced by naloxone pretreatment or reversed by subsequent injection of naloxone. Differences in hyperthermic patterns over a range of Tas and the lack of hypothermogenic action of morphine indicate that DAME alters thermoregulation in the cat by acting on morphine-insensitive, but naloxone-sensitive, receptors. Central injection of β-endorphin (5–50 μg) caused a dose-related hyperthermia. (Des-tyr1)-leucine-enkephalin (10–250 μg) was weakly hyperthermogenic, and kyotorphin (500 μg) did not consistently alter body temperature.
Processing of visual and name codes in good and poor readers

Abstract Good and poor readers of three different ages (7, 9, and 11 years) were required to respond to stimuli which could be matched by physical similarity (e.g., A-A ) or by name (e.g., A-a ). It was argued that these two matches allow for the differentiation of two primary levels of processing required of a visual input. Both age and reading competence proved to be significant variables in relationship to the time required for the physical and name matches. The lack of a significant age or reading competence interaction with the type of match (physical or name) made the deficiency present in the name match difficult to interpret. However, data were discussed which indicate that poor readers are less efficient in anticipating the form required in the name match. This inability to reduce required visual processing through anticipation may reflect a general processing deficiency of the poor reader.
Phenylbutyrate-induced G1 arrest and apoptosis in myeloid leukemia cells: structure-function analysis.

Phenylbutyrate-induced G1 arrest and apoptosis in myeloid leukemia cells: structure–function analysis
High output power 1540 nm vertical cavity semiconductor optical amplifiers

Vertical cavity semiconductor optical amplifiers operating at 1540 nm are presented. The use of AlInGaAs multiple quantum well active regions resulted in record-high saturation output power of +0.5 dBm and 16 dB of fibre-to-fibre gain. These results were achieved in reflection mode operation using optical pumping by a 980 nm semiconductor laser.
The Origin of Cosmic Rays

The original idea of Menzel and Salisbury concerning the origin of cosmic rays has been extended and some of its possible consequences worked out in more detail. It is concluded that low frequency electromagnetic waves (a few cycles per second) may exist in limited regions near the outer edge of the solar corona, and could accelerate ions to cosmic-ray energies. An attempt is made to explain both the "ordinary" cosmic rays and the intensity increases following solar flares in terms of the action of these waves.
Measurement of Thermal Time Constant in 65-nm PD-SOI Technology with Sub-ns Resolution

In PD-SOI the oxide layer between MOSFETs and the underlying silicon substrate presents a thermal resistance that can lead to significant temperature rise for power dissipating devices. This can impact circuit performance and also introduce differences between device characteristics measured under DC conditions and those experienced under "at speed" operating conditions with low duty cycles common for CMOS circuits. Here a new technique for measuring the thermal time constant of PD-SOI MOSFETs in an adjacent heating configuration with sub-ns time resolution is presented. Experimental results for specific layouts in experimental 65 nm PD-SOI hardware show time constants of order 20 - 30 ns.
Future prospects in magnetic resonance imaging

Cardiovascular magnetic resonance (CMR) is widely regarded as capable of providing a cornucopia of detailed diagnostic information. However, of that information, very little is truly unique, and can be obtained by a combination of alternate diagnostic modalities. Given this, it is anticipated that in the short term (1-5 years) CMR will find use primarily as a modality to service patients whose diagnosis is inaccessible to established technologies such as ultrasound and radionuclide imaging. Due to the evolving emphasis on finding new and more efficient approaches to disease detection and prevention, as outlined in a policy-setting speech given by the director of the National Institutes of Health, it is anticipated that the scientific and clinical trial communities will adopt CMR at a more rapid pace due to its inherent dimensional accuracy and comprehensive nature. CMR is particularly well suited to participate in the approaching explosion of nanoparticle technologies, as they are applied to diagnostic and therapeutic approaches. In the longer term (5-10 years), as paradigms of disease detection likely expand beyond evaluation of symptoms and risk factors, the comprehensive nature of information provided by CMR will drive the increase of its use as a primary, first-tier, diagnostic modality. In summary, the use of CMR will become increasingly common, and as understanding of disease processes expand, it will emerge as a diagnostic modality that provides an abundance of unique information.