cssi/SciSciGPT-SciSciNet huggingface dataset:
Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer.

Objective Patients with epithelial ovarian cancer (EOC) typically present with late-stage disease, posing a significant challenge to treatment. Although taxane and platinum-based chemotherapy plus surgical debulking are initially effective, EOC is marked by frequent recurrence with resistant disease. Immunotherapy represents an appealing treatment paradigm given the ability of immune cells to engage metastatic sites and impede recurrence; however, response rates to checkpoint blockade in ovarian cancer have been disappointing. Here, we tested whether class I HDAC inhibition can promote anti-tumor T cell responses in a spontaneous and nonspontaneous murine model of EOC. Methods We used the spontaneous Tg-MISIIR-Tag and nonspontaneous ID8 models of murine ovarian cancer to test this hypothesis. Whole tumor transcriptional changes were assessed using the nCounter PanCancer Mouse Immune Profiling Panel. Changes in select protein expression of regulatory and effector T cells were measured by flow cytometry. Results We found that treatment with the class I HDAC inhibitor entinostat upregulated pathways and genes associated with CD8 T cell cytotoxic function, while downregulating myeloid derived suppressor cell chemoattractants. Suppressive capacity of regulatory T cells within tumors and associated ascites was significantly reduced, reversing the CD8-Treg ratio. Conclusions Our findings suggest class I HDAC inhibition can promote activation of intratumoral CD8 T cells, potentially by compromising suppressive networks within the EOC tumor microenvironment. In this manner, class I HDAC inhibition might render advanced-stage EOC susceptible to immunotherapeutic treatment modalities.
Perceived Faultlines in Group Dynamics: An Individual-Level Perspective:

The authors elaborate a multilevel model of faultline perceptions across individuals in groups. They develop the concept of individual perceived faultlines and build logic about an individual-level...
Idaho database of solution thermodynamics

Abstract The “Idaho Database of Solution Thermodynamics” (IDST, https://idst.inl.gov/ ) was created by collecting literature vapor liquid equilibrium (VLE) data in the form of practical osmotic coefficients, ϕ m , and solute molal activity coefficients, γ B ( m ) , for binary solutions (solute-solvent). These values, corresponding to isothermal vapor pressure measurements, were collated from literature sources to further research involving concentration dependent solution properties. The initial data cohort includes 473 aqueous datasets and 121 non-aqueous datasets from 119 references. This data has been made publicly available in a graphically, tabularly, and machine-readable forms in a variety of concentration and property units.
Pandemic Pedagogy for the New Normal: Fostering Perceived Control During COVID-19

Before the pandemic, loneliness was already a burden affecting the health and well-being of students. The COVID-19 pandemic, with mandated isolations and closures of campuses, amplifies feelings of...
Patient Health Outcomes following Dialysis Facility Closures in the United States.

Background Ongoing changes to reimbursement of United States dialysis care may increase the risk of dialysis facility closures. Closures may be particularly detrimental to the health of patients receiving dialysis, who are medically complex and clinically tenuous. Methods We used two separate analytic strategies-one using facility-based matching and the other using propensity score matching-to compare health outcomes of patients receiving in-center hemodialysis at United States facilities that closed with outcomes of similar patients who were unaffected. We used negative binomial and Cox regression models to estimate associations of facility closure with hospitalization and mortality in the subsequent 180 days. Results We identified 8386 patients affected by 521 facility closures from January 2001 through April 2014. In the facility-matched model, closures were associated with 9% higher rates of hospitalization (relative rate ratio [RR], 1.09; 95% confidence interval [95% CI], 1.03 to 1.16), yielding an absolute annual rate difference of 1.69 hospital days per patient-year (95% CI, 0.45 to 2.93). Similarly, in a propensity-matched model, closures were associated with 7% higher rates of hospitalization (RR, 1.07; 95% CI, 1.00 to 1.13; P=0.04), yielding an absolute rate difference of 1.08 hospital days per year (95% CI, 0.04 to 2.12). Closures were associated with nonsignificant increases in mortality (hazard ratio [HR], 1.08; 95% CI, 1.00 to 1.18; P=0.05 for the facility-matched comparison; HR, 1.08; 95% CI, 0.99 to 1.17; P=0.08 for the propensity-matched comparison). Conclusions Patients affected by dialysis facility closures experienced increased rates of hospitalization in the subsequent 180 days and may be at increased risk of death. This highlights the need for effective policies that continue to mitigate risk of facility closures.
2020 New Employer Business Indicators in the United States: National and State Trends

The Kauffman New Employer Business Indicators series has been compiled in an effort to provide information on new employer businesses, a subset of all entrepreneurial activity. The series provides users with measures to track trends surrounding the emergence of these businesses, their representation in the population and among all firms, and the time it takes these businesses to become employers. The indicators are constructed using publicly available data from three administrative data sources – the Business Formation Statistics, Business Dynamics Statistics, and Population Estimates Program. These sources include data on people, and new and established businesses, at the state and national level, and can include projected data for some years. This report presents national and state trends in new employer businesses in the United States.
Thermal Analysis for Phenolic Impregnated Carbon Ablator/CV-1144-0 in Hypersonic Test Environments

Analysis of multidimensional in-depth thermal response for the phenolic impregnated carbon ablator (PICA)/CV-1144-0 material system in NASA Langley Research Center Hypersonic Materials Environmenta...
Characterizing the direct care health workforce in the United States, 2010-2019.

Background To describe the growth and characteristics of the direct care health workforce, encompassing home health aides, personal care aides, nursing assistants, and orderlies and psychiatric aides from 2010 to 2019 in the United States. Methods Using nationally representative data from the 2010 to 2019 American Community Survey, we described the growth in the direct care health workforce overall and by type of direct care health worker. In addition, we examined the distribution of direct care workers by geographic region of the country, age categories, citizenship, world area of birth, income, health insurance status, and other characteristics. Results From 2010 to 2019, the number of direct care health workers in the United States per 10,000 individuals decreased slightly from 135.81 in 2010 to 133.78 in 2019. Personal care aides made up 42.1% of the direct care health workforce in 2019, followed by nursing assistants (39.5%) and home health aides (16.3%). In 2019, the number of direct care health workers who were not U.S. citizens accounted for roughly 10% of all workers in each year. The relative percentage of direct care health workers that were not a citizen of the United States was highest among home health aides (16.3%). Among workers born outside of the United States, the majority were from Latin America, followed by Asia. Conclusion From 2010 to 2019, there was little growth in the direct care health workforce despite growing demand for direct care health workers. In the midst of the current and projected shortage of direct care health workers-particularly during the COVID-19 pandemic, longer-term solutions to improve retention of direct care health workers and increase the supply of direct care health workers may be needed.
Fixed-site-carrier facilitated transport of carbon dioxide through ionic-liquid-based epoxy-amine ion gel membranes

Abstract The amine functional groups in room-temperature ionic liquid (RTIL)-based epoxy-amine ion gel membranes allow for the fixed-site-carrier facilitated transport of CO 2 . These membranes were tested under humidified mixed-gas (CO 2 /N 2 ) feeds in order to evaluate the effects of relative humidity, CO 2 partial pressure, and hydrophobicity of the added free RTIL on CO 2 /N 2 separation performance. Changes in relative humidity were found to have little effect on CO 2 /N 2 separation performance at constant CO 2 partial pressure. However, comparison to dry-gas measurements showed that the presence of water vapor is necessary to observe facilitated CO 2 transport in these systems. Increased CO 2 permeability and CO 2 /N 2 selectivity were observed for these epoxy-amine ion gel membranes with decreasing CO 2 partial pressure, as expected for materials operating via the fixed-site-carrier facilitated transport mechanism. The hydrophilicity of the free RTIL was found to influence CO 2 transport, with a more hydrophilic RTIL able to facilitate CO 2 transport at lower relative humidity. Facilitated transport enhances the CO 2 /N 2 separation performance of these epoxy-amine ion gel membranes and enables them to exceed the 2008 Robeson plot upper bound.
A novel localization and coverage framework for real-time participatory urban monitoring

Participatory sensing is a powerful paradigm in which users participate in the sensing campaign by collecting and crowdsourcing fine-grained information and opinions about events of interest (such as weather or environment monitoring, traffic conditions or accidents, crime scenes, emergency response, healthcare and wellness management), thus leading to actionable inferences and decisions. Based on the nature of user involvement, participatory sensing applications can be of two types-automated and user manipulated. The first type of applications automatically collects data samples from smartphone sensors and sends them to the server. On the other hand, the second type of applications depends on the users to manually collect data samples and upload them at their convenience. Because of the high density of smartphone users in urban population and ease of participation, the automated participatory sensing paradigm can be effectively applied to continuous monitoring of various phenomena in urban scenarios (e.g., fine-grained temperature monitoring, noise or air pollution), leading to what is called participatory urban sensing. However, for creating a fine-grained and real-time map of the monitored area, the data samples need to be collected continuously (at a high frequency) which poses several research challenges. First, how to ensure coverage of the collected data that reflects how well the targeted area is monitored? Second, how to localize the smartphones since continuous usage of the location sensor (e.g., GPS) can drain the battery in few hours? Third, how to provide energy efficiency in the data collection process by collecting necessary data samples in each data collection round? In this article, we propose a novel framework called PLUS to address three major issues in real-time participatory urban monitoring applications, namely, ensuring coverage of the collected data, localization of the participating smartphones, and overall energy efficiency of the data collection process. Specifically the PLUS framework can guarantee a specified requirement of partial data coverage of the monitored area in an energy efficient manner. Additionally we devised a Markov-Predictor based energy efficient outdoor localization scheme for the mobile devices to participate in the data collection process. Simulation studies and real life experiments exhibit that PLUS can significantly reduce energy consumption of the mobile devices for urban monitoring applications as compared to traditional approaches.
Morphogenesis and calcification of the statoconia in the chick (Gallus domesticus) embryo: implications for future studies.

The morphogenesis of the statoconia in the chick, Gallus domesticus, injected with a carbon anhydrase inhibitor is studied. The preparation of the embryo specimens for analysis is described. The early, middle, and late stages of embryonic development are examined. The data reveal that acetozolamide inhibits statoconia formation in the middle stage of development and the calcification process follows statoconia formation. The spatial relationship between the development of type 1 and type 2 hair cells and the appearance and maturation of the statoconia is investigated.
Interactions of standard antibody with Australia antigens in Au Ag-Ab radioimmunoassay.

Human antisera against Australia (Au) antigen have been characterized by liquid-phase radioimmunoassay (RIA) for their precipitation of 125I-labeled Au antigen. The end-point dilutions of sera (anti-Au) which precipitated 50% of 125I-Au antigen by RIA correlated well with complement fixation titers but had a much wider range, indicating a greater precision and perhaps a better sensitivity of assay. Anti-Au serum diluted to precipitate 50% of 125I-labeled Au antigen was used as standard antibody in RIA tests to detect either inhibition or enhancement of the reaction by preincubated mixtures of Au antigen and antibody specimens. Without free Au antigen or antibody in the resultant mixtures there was no inhibition or enhancement; the mixtures presumably contained immunoreactively equivalent proportions of Au antigen and antibody. RIA data for diagnostic specimens indicated an end-point sensitivity which was proportional to the dilution of the standard anti-Au sera used in the test. High concentrations of the standard antibody permitted detectable inhibition of 125I-Au antigen precipitation at lower antigen specimen concentrations. Similarly, low concentrations of the standard antibody permitted detectable enhancement of 125I-Au antigen precipitation at lower antibody specimen concentrations. Omitting the standard antibody altogether resulted in a more sensitive RIA for Au antibody in test sera.
Impact of 20 Years of Land‐Cover Change on the Hydrology of Streams in the Southeastern United States1

Cruise, James F., Charles A. Laymon, and Osama Z. Al-Hamdan, 2010. Impact of 20 Years of Land-Cover Change on the Hydrology of Streams in the Southeastern United States. Journal of the American Water Resources Association (JAWRA) 46(6):1159–1170. DOI: 10.1111/j.1752-1688.2010.00483.x Abstract: Land-cover changes for portions of Alabama, Georgia, and Tennessee were estimated for the years 1980, 1990, and 2000 using classified Landsat images, and associated with hydrologic indices for 12 watersheds in the region. Rainfall-adjusted mean annual streamflow, an ET proxy (precipitation minus runoff), frequency of inundation above thresholds, and duration of inundation were used to characterize the hydrologic response of the test basins over the two-decade study period. Results indicate that several of the watersheds had undergone significant (>20%) reductions in agricultural land cover with a coincident increase in forested land. Attempts to correlate the hydrologic results with the land-cover changes were only partially successful. Watersheds with the largest land conversion from agriculture to forest (20% or more) did show significant trends in hydrologic indices indicating decreasing streamflow; however, other basins evidenced ambiguous results. The net conclusions of the study are that land-cover effects on hydrologic variables may be nuanced and can sometimes be only indirectly evident, and that a rigorous and detailed land-cover classification effort along with a battery of statistical tests with the same objective may be necessary to uncover these effects.
Drying gels: VIII. Revision and review

Abstract In Part I of this series, a method was presented for analysis of the stresses that develop during drying of a porous body, such as a gel. That formulation did not take propert account of the effect of local variations in network shrinkage on the pressure in the liquid. In this paper, an improved analysis is presented. The form of the original equations is generally preserved, except that the pressure in the liquid is shown to depend on both the shear and bulk moduli (or viscosities), rather than simply on the bulk modulus (or viscosity). The present modification is most important for the case of a warping plate or a film on a rigid substrate. The connection of this model with those of Biot and others is discussed.
An Alleged Yeast Polyphosphate Kinase Is Actually Diadenosine-5′,5‴-P1,P4-tetraphosphate α,β-Phosphorylase

Polyphosphates are a major constituent of the yeast Saccharomyces cerevisiae. A purification of the enzyme polyphosphate kinase (E.C. 2.7.4.1) from this organism has been reported (Felter, S., and Stahl, A.J.C. (1973) Biochimie (Paris) 55, 245-251). The assay for activity used in this purification was the production of 32P-labeled nucleotide, presumed to be ATP, in the presence of [32P]polyphosphate and ADP. We have found that this assay does not reflect the activity of a polyphosphate kinase but rather the combination of an exopolyphosphatase, releasing free [32P]phosphate from the added [32P]polyphosphate, and the ADP-[32P]phosphate exchange activity of the enzyme diadenosine 5',5"'-P1, P4-tetraphosphate alpha, beta-phosphorylase (Ap4A phosphorylase). We also present direct evidence for the formation of an enzyme-AMP intermediate in the actin of Ap4A phosphorylase.
Sex, Drugs, and Violence: Neuromodulation of Attachment and Conflict in Voles

Prairie voles (Microtus ochrogaster) are a rodent species that display socially monogamous pair-bonds, a behavior illustrated by several types of social interactions such as mating-induced partner preference, selective aggression toward conspecific strangers, and bi-parental care. Therefore, this species has provided an excellent opportunity for the study of pair-bonding and its underlying neurochemical mechanisms. This chapter discusses the utility of this unique rodent in the study of attachment and conflict, and reviews recent findings illustrating the neuromodulatory mechanisms underlying mating-induced partner preference and aggression. Finally, implications of research using this animal model in human mental health are also discussed.
Model-free analysis of quadruply imaged gravitationally lensed systems and substructured galaxies

Multiple image gravitational lens systems, and especially quads are invaluable in determining the amount and distribution of mass in galaxies. This is usually done by mass modeling using parametric or free-form methods. An alternative way of extracting information about lens mass distribution is to use lensing degeneracies and invariants. Where applicable, they allow one to make conclusions about whole classes of lenses without model fitting. Here, we use approximate, but observationally useful invariants formed by the three relative polar angles of quad images around the lens center to show that many smooth elliptical+shear lenses can reproduce the same set of quad image angles within observational error. This result allows us to show in a model-free way what the general class of smooth elliptical+shear lenses looks like in the three dimensional (3D) space of image relative angles, and that this distribution does not match that of the observed quads. We conclude that, even though smooth elliptical+shear lenses can reproduce individual quads, they cannot reproduce the quad population. What is likely needed is substructure, with clump masses larger than those responsible for flux ratio anomalies in quads, or luminous or dark nearby perturber galaxies.
The evolution of preference strength under sensory bias: a role for indirect selection?

Evidence suggests that female preferences may sometimes arise through sensory bias, and that males may subsequently evolve traits that increase their conspicuousness to females. Here, we ask whether indirect selection, arising through genetic associations (linkage disequilibrium) during the sexual selection that sensory bias imposes, can itself influence the evolution of preference strength. Specifically, we use population genetic models to consider whether or not modifiers of preference strength can spread under different ecological conditions when female mate choice is driven by sensory bias. We focus on male traits that make a male more conspicuous in certain habitats—and thus both more visible to predators and more attractive to females—and examine modifiers of the strength of preference for conspicuous males. We first solve for the rate of spread of a modifier that strengthens preference within an environmentally uniform population; we illustrate that this spread will be extremely slow. Second, we used a series of simulations to consider the role of habitat structure and movement on the evolution of a modifier of preference strength, using male color polymorphisms as a case study. We find that in most cases, indirect selection does not allow the evolution of stronger or weaker preferences for sensory bias. Only in a “two-island” model, where there is restricted migration between different patches that favor different male phenotypes, did we find that preference strength could evolve. The role of indirect selection in the evolution of sensory bias is of particular interest because of ongoing speculation regarding the role of sensory bias in the evolution of reproductive isolation.
Interleukin-7 deficiency in rheumatoid arthritis

Interleukin-7 (IL-7) is a stromal factor that is crucial for the development of T lymphocytes in humans and mice, and also B lymphocytes in mice. IL-7 can act as a T cell growth factor as well as a critical anti-apoptotic survival factor. The essential non-redundant role of this cytokine for T cell development in vivo is indicated by the phenotype of murine knockout models as well as by humans with a T-B+NK+ form of severe combined immunodeficiency (SCID) resulting from mutations in IL-7 receptor α chain. IL-7 deficiency has now been found in patients with rheumatoid arthritis, a finding that relates not only to the T-lymphocyte status in this disease but also to the ability of patients with rheumatoid arthritis to recover from therapy-induced lymphopenia.
Digital subtraction rotational angiography for aneurysms of the intracranial anterior circulation: injection method and optimization.

PURPOSE To optimize parameters of rotational angiography for examination of the internal carotid circulation; to compare rotational angiography with standard digital subtraction angiography (DSA) in the evaluation of aneurysms of the intracranial internal carotid circulation; and to determine tolerance and safety limits of prolonged internal carotid injection angiography. METHODS Rotational angiograms were obtained during injection of the internal carotid circulation as part of the clinical angiographic evaluation of aneurysms in 41 patients. Injection rates, X-ray delays, and fields of view were studied retrospectively. Findings at rotational angiography and standard DSA were compared. Nonionic contrast material was injected over 6 seconds, and patients were studied before and after prolonged injection angiography by physical and laboratory examination, including measurement of blood pressure, pulse, and intracranial pressure. RESULTS Vascular conspicuity was equivalent at carotid injection rates of 4 and 5 mL/s delivered over 6 seconds. At 3 mL/s, more image manipulation was required to see small vascular structures. One-second X-ray delay combined with 6-second injection duration provided the best arterial depiction of intracranial vessels from start to end of rotational angiography. Maximal rotational resolution was with a 17-cm field of view. Identification of aneurysms and small vessels was equivalent at all injection rates. Aneurysm detection was equivalent with rotational angiography and DSA. In 9 of 31 aneurysms, the neck was defined more clearly with rotational angiography than with DSA, compared with 2 of 31 that were seen better with DSA. Aneurysms of the intracranial internal carotid circulation were seen with rotational angiography and not DSA in 12 of 41 cases. No change was noted in clinical or laboratory findings. CONCLUSION Rotational angiography provided better definition of the aneurysmal neck and greater clarity of aneurysms than did DSA; it also improved the level of confidence in predicting the presence or absence of aneurysms, especially in the anterior communicating artery; however, in our small series it did not significantly increase the detection of aneurysms. Prolonged injection angiography was well tolerated in all patients.
On the Reception of Quasi-Monochromatic, Partially Polarized Radio Waves

The response of an elliptically polarized antenna to a quasi-monochromatic, partially polarized radio wave is treated from the standpoint of coherence theory. A general formula is derived for the available power at the terminals of a receiving antenna in terms of appropriately chosen coherency matrices for the antenna and the incident wave. It is shown that the result is formally identical with the basic interference law of partially coherent, quasi-monochromatic wave fields. Conditions for the maximum available power are discussed, and a geometrical interpretation of the result is given. The coherency matrix for the antenna is determined uniquely in terms of the transmitting properties of the antenna. It is shown that the coherency matrix formalism for the interaction of an antenna with an incident wave fits very well with those used in the modern theory of optics and quantum mechanics. A new definition for the antenna effective aperture using the coherency matrix is suggested, which takes into account the polarization property of the antenna.
1020-4 Proximal Isovelocity Surface Area Method Applied to Non-Planar Surfaces: Implications of In Vitro Studies for Clinical Regurgitation and Stenosis

The color Doppler proximal isavelocity surface area (PISA) method accurately estimates volume flow rate (Q) across a planar surface in vitro. This method has been applied clinically to estimating valvular regurgitant flow using a hemispherical formula requiring measurement of a single axial radius. However, since cardiac valves may approximate convex shape, the most accurate PISA formula for calculating Q across a valve should be different from that for a planar model. We evaluated variations of PISA formula in a planar model and two convex-shaped models. Methods Three circular orifice diameters (O = 5.2, 8, 12 mm) on hemispherical bails (diameter, D = 38 and 58 mm) and one planar model were studied in a constant flow system (Fig. 1). The radii (A and B) of PISA were measured in axial and transverse views. Flow velocity and actual Q across orifices were varied from 0.3–7.7 m/s and 0.9–8.6 l/min, respectively. Results 1) B/A ratios were dependent on actual Q and orifice sizes. 2) B/A ratios were significantly larger for convex models than for a planar model at actual Q below 5 l/min (p l 0.001) (Fig.2 shows data for orifice O = 8 mm at aliasing velocity between 15 and 30 cm/s). 3) In a convex model (D = 38 mm), B/A ratios for orifices O = 5.2,8,12 mm at actual Q = 1.5 l/min were 1.35 ± 0.07, 1.62 ± 0.07 and 1.85 ± 0.08, respectively (p l 0.001). The D = 58 mm convex model demonstrated similar results. Conclusion The shape of PISA for a convex surface is less hemispherical than for a planar surface. Decreased axial radius is partially compensated for by increased transverse radius. Since precise orifice geometry is often unknown clinically, measurement of both PISA axial and transverse radii is important to minimize under-estimation of regurgitant or stenotic flow Download : Download high-res image (92KB) Download : Download full-size image Download : Download high-res image (90KB) Download : Download full-size image
A 3–20 GHz SiGe HBT ultra-wideband LNA with gain and return loss control for multiband wireless applications

We present an ultra-wideband, Low Noise Amplifier (LNA) implemented in Silicon-Germanium Heterojunction Bipolar Transistor (SiGe HBT) technology. This SiGe LNA is broadband, covering the frequency range of 3–20 GHz, and achieves a peak gain of 21.3 dB. The SiGe LNA exhibits a Noise Figure (NF) of 4.2–5.2 dB across an 8–18 GHz band and consumes 35.2 mA from a 3.3 V supply.
State abortion policy and infant health: A simulation model of the impact of hypothetical patterns of state laws proscribing abortion services

Prior research suggests that the availability of abortion services may affect the proportion of observed births with poor outcomes (e.g., low birth weight). Recent Supreme Court decisions and changes in the composition of elected officials of state governments have increased the saliency of state discretion over abortion related policies. This paper presents results from a simulation model of the effects of hypothetical state laws prohibiting abortion on observed measures of infant health in the states regarded as most likely to adopt laws significantly restricting abortion access. Under several model scenarios, both the incidence of low birthweight infants and neonatal mortality among blacks are predicted to increase substantially in states adopting restrictive abortion laws. The predicted impact among whites, however, is relatively small.
Practical consequences of the assessment of different energy health risks

Abstract Public authorities must make decisions about energy, and the risks of alternative strategies need to be calculated including health and environmental costs. Information from various sources must be organized into a logical framework for comparing impacts. This must include the widest practicable range of health and environmental damage — public-health impact of pollution, role of accidents, disease and hazardous materials in the workplace, and odds for catastrophes. It must put each part of the energy cycle into perspective-giving particular attention to uncertainties in knowledge - to convey what is known, what is uncertain, and the importance of each factor in the overall picture. This paper gives examples of the use of health-impact assessment by decisionmakers: (1) comparative risk assessment of the health effects of coal and nuclear fuel cycles used in nuclear power plant siting and licensing hearings, and (2) health risks of acid deposition and other air-transported pollutants, carried out as part of an assessment for the U.S. Congress Office of Technology Assessment.
Pharmacology of Local Anesthetics

A S MY WIFE (an ophthalmologist) is always eager to point out, the major discoveries in anesthesia were made by surgeons. Although debatable in the general field of anesthesiology, the initial utilization of local anesthetics is certainly attributable to surgeons. The first documented use of local anesthesia for surgery was made by Carl Koller on September 11, 1884, when he demonstrated ocular surface anesthesia with the application of cocaine and performed an operation for glaucoma. (August Bier, a German surgeon, performed the first spinal anesthetic in 1899, also with cocaine. He also described the first postdural puncture headache immediately afterward.) By November 1884, the ophthalmologist C.S. Bull had reported on his use of cocaine as a topical anesthetic for surgery on the cornea and conjunctiva for 150 cases. Over the next 100 years and leading to today, the uses and types of local anesthetics have grown enormously, as has our understanding of the mechanism of action of this class of drug. As practitioners utilizing these agents, the safe and effective use depends on our understanding of the pharmacology, specific uses, and toxicity of the various local anesthetics available today.
DIFFUSION AND SURVIVAL OF THE POLIOMYELITIC VIRUS.

The ordinary virus of poliomyelitis present in aseptically removed brain tissue of paralyzed monkeys survives in an ascitic fluid kidney medium at the temperature of 37°C. for a period of at least twenty, but not of thirty days. Under the conditions of moderate anaerobiosis, the minute microorganism cultivated from poliomyelitic tissues tends not to develop in cultures from the brain tissue; hence its presence does not complicate the survival test. The diffusion of the ordinary poliomyelitic virus from a noncomminuted fragment of brain tissue into a surrounding medium of ascitic fluid is so slight as not to be detectable by inoculation experiments conducted with usual quantities of the fluid. The specific effects of the microorganism cultivated from poliomyelitic tissues are not caused by an admixture in the cultures of the ordinary virus of poliomyelitis; hence they must be caused by the pathogenic action of the microorganism itself. The minute microorganism is therefore to be regarded as the specific microbic cause of epidemic poliomyelitis.
Paying for What Ails You: Sociocultural Issues Influencing the Ways and Means of Therapy Payment in South India

Illness costs in many different ways: in time, cash, emotions, social relations and choices. Economic considerations are commonly cited as important determinants of when and how people choose to use the services of different types of practitioners in pluralistic health care arenas. Perhaps because economic considerations are such obvious factors influencing health care decision-making, they are often over-looked as a subject for rigorous qualitative research. There is a poverty of research on both how much the poor spend on various illnesses experienced by different family members (by age and gender) and what the costs of illness in time, disposable income and loans mean in terms of family life and health. Even less research has been conducted on patterns of payment for health care services and the social factors influencing these patterns. It is the social relations of paying for therapy and asking for fees which will be the focus of this chapter.
Integrated liquid-core optical fibers for ultra-efficient nonlinear liquid photonics

We have developed a technique that allows splicing of liquid core optical fiber (LCOF) to standard fiber with low loss. As an example, we demonstrated ultralow threshold Raman generation in an integrated CS 2 filled LCOF.
Effect of Monomer Functionality on the Morphology and Performance of the Holographic Transmission Gratings Recorded on Polymer Dispersed Liquid Crystals

Transmission gratings were formed holographically in polymer dispersed liquid crystal (HPDLC) composite materials using commercially available UV-curable acrylate monomers and the nematic liquid crystal TL203. Monomer mixtures with average functionality ranging from 1.3 to 3.5 were used to prepare HPDLC transmission gratings. The phase-separated morphology and surface topology of the transmission gratings as observed through scanning electron microscopy and atomic force microscopy varied profoundly with the different monomer mixtures characterized by their average functionalities. The switching properties of the HPDLC gratings were correlated with the morphological changes.
Analysis of C- V data in the accumulation regime of MIS structures

Abstract Hynecek's method for deriving flat band from C - V data of MIS structures in the accumulation regime is modified to provide a precise determination of the insulator capacitance. The effect of interface states on flat band determination is discussed and it is shown that an upper limit on the surface state density can be obtained from high frequency measurements in the accumulation regime without requiring the substrate dopant concentration.
Viral Induced CD28 Loss Evokes Costimulation Independent Alloimmunity

Abstract Background Belatacept, a B7-specific fusion protein, blocks CD28-B7 costimulation and prevents kidney allograft rejection. However, it is ineffective in a sizable minority of patients. Although T-cell receptor and CD28 engagement are known to initiate T-cell activation, many human antigen-experienced T-cells lose CD28, and can be activated independent of CD28 signals. We posit that these cells are central drivers of costimulation blockade resistant rejection (CoBRR) and propose that CoBRR might relate to an accumulation of CD28 − T-cells resulting from viral antigen exposure. Materials and methods We infected C57BL/6 mice with polyomavirus (a BK virus analog), murine cytomegalovirus (a human cytomegalovirus analog), and gammaherpesvirus (HV68; an Epstein–Barr virus analog) and assessed for CD28 expression relative to mock infection controls. We then used mixed lymphocyte reaction (MLR) assays to assess the alloreactive response of these mice against major histocompatibility complex-mismatched cells. Results We demonstrated that infection with polyomavirus, murine CMV, and HV68 can induce CD28 downregulation in mice. We showed that these analogs of clinically relevant human viruses enable lymphocytes from infected mice to launch an anamnestic, costimulation blockade resistant, alloreactive response against major histocompatibility complex-mismatched cells without prior alloantigen exposure. Further analysis revealed that gammherpesvirus–induced oligoclonal T-cell expansion is required for the increased alloreactivity. Conclusions Virus exposure results in reduced T-cell expression of CD28, the target of costimulation blockade therapy. These viruses also contribute to increased alloreactivity. Thus, CD28 downregulation after viral infection may play a seminal role in driving CoBRR.
Cyclic Peptides as Molecular Adapters for a Pore-Forming Protein

Recently, cyclodextrins were shown to act as adapters for the pore-forming protein staphylococcal α-hemolysin (αHL). The bagel-shaped molecules bind in the lumen of the transmembrane channel formed...
Studies on the accuracy of time-integration methods for the radiation-diffusion equations

The governing equations for the radiation-diffusion approximation to radiative transport are a system of highly nonlinear, multiple time-scale, partial-differential equations. The numerical solution of these equations for very large-scale simulations is most often carried out using semi-implicit linearization or operator-splitting techniques. These techniques do not fully converge the nonlinearities of the system so as to reduce the cost and complexity of the transient solution at each time step. For a given time-step size, this process exchanges temporal accuracy for computational efficiency. This study considers the temporal-accuracy issue by presenting detailed numerical-convergence studies for problems related to radiation-diffusion simulations. In this context a particular spatial discretization based on a Galerkin finite-element technique is used. The time-integration methods that we consider include: fully implicit, semi-implicit, and operator-splitting techniques. Results are presented for the relative accuracy and the asymptotic order of accuracy of the various methods. The results demonstrate both first-order and second-order asymptotic order of accuracy for the fully implicit, semi-implicit, and the operator-splitting schemes. Additionally a second-order operatorsplitting linearized-diffusion method is also presented.
Charges and bond orders in covalent xenon compounds using the structure—resonance paradigm

Abstract An empirical structure-resonance theory model for the xenon fluorides and oxyfluorides is examined, and quantitative estimates of atom charges and bond orders are derived. The results are correlated with other theoretical estimates and with related experimental properties. Realistic representations of molecular structures for the compounds containing xenon with higher oxidation states require that large numbers of octet structures, ionic resonance forms and/or expanded valence shell structures contribute to the final resonance hybrids. The representation of the effective structure—resonance theory Hamiltonian matrix by a graph allows the resulting high dimension eigenproblem to be greatly reduced using graph theoretical topological and symmetry restraints. XeF bond orders and fluorine atom charges are found to show little variation over the entire range of xenon oxidation state. The calculated xenon charges are generally much smaller but proportional to the formally assigned oxidation numbers.
Diazocyclopentadiene (DACP), a light sensitive reagent for the ethylene receptor in plants

Diazocyclopentadiene (DACP) has been shown to be an effective reagent for the ethylene receptor. Treatment of mung bean sprouts or tobacco leaves with DACP in the light or in the dark inactivates much of the ethylene binding. In the light, inactivation seems to be permanent, while in the dark, the site becomes active again after the DACP diffuses away. The compound is 10 times more effective in the light than in the dark. DACP inhibits banana ripening indicating the physiological receptor is involved. It also overcomes the inhibitory effect of ethylene on mung bean seedling growth (Km = 0.09 µl/1 E) at low ethylene levels. At high ethylene levels, an apparent high ethylene level site becomes apparent (Km = 50 µl/1 E) and growth is inhibited.
Eclosion hormone may control all ecdyses in insects

The moulting process in insects is initiated and directed by the hormone 20-hydroxyecdysone1, which causes the secretion of a new cuticle and the internal changes that are necessary for the new stage. When the new cuticle is complete, the old one is then shed or ecdysed. In Lepidoptera a neurosecretory peptide, eclosion hormone (EH)2–4, triggers adult ecdysis by acting on the central nervous system to elicit the ecdysial motor programmes5 and also causes other physiological changes associated with ecdysis6. Although it was originally thought that EH was used only for the rather specialized adult ecdysis3, we report here that the hormone is used for all postembryonic ecdyses in the life history of moths, but its source varies with developmental stage. Moreover, EH may be common to a wide variety of insects. For the ecdyses of the adult4, pupa7 and the 5th instar larva of the tobacco hornworm, Manduca sexta (P.F.C., unpublished results), EH appeared in the blood before the start of the behaviour. Also, injections of partially purified EH caused precocious ecdysis of the three stages with 50% responses occurring at 0.3, 0.02 and 0.01 EH units, respectively.
Postoperative delirium in elderly patients.

OverviewNearly 40% of all surgeries in the United States are performed on adults ages 65 and older. One of the most common surgical complications in this population is postoperative delirium, which is associated with extended lengths of stay, higher patient care costs, increased morbidity, and great
CT Imaging of a Pancreatic Pseudocyst: Clinical and Anatomic Implications

We report the case of a 42-year-old man with a large pancreatic pseudocyst, the presence of which was not suspected upon initial presentation. This case provides an example of when imaging may be useful for the detection of pancreatitis and its complications. It also demonstrates classic pseudocyst localization to the lesser sac and left anterior pararenal space. The unusually large size of this pseudocyst provides a clear delineation of retroperitoneal fascial planes and an illustration of possible clinical consequences of mechanical obstruction by pseudocyst.
Homogeneous groups and multiscale intensity models for multiname credit derivatives

We discuss a computationally tractable approach to the valuation of multiname credit derivatives employing name grouping for dimension reduction, and singular perturbation approximations for model robustness. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Kyou-sou in the Nippon baseball leagues

There is a well-established long-term trend towards increased competitive balance in US major-league baseball. Kyou-sou (competing) in the Nippon leagues has been on a similar upward trend. Nippon baseball, however, has not undergone the substantive institutional changes that mark the major leagues. After accounting for some of the factors that might explain this upward trend and eliminating some other plausible explanations, it is concluded that the greater competitive balance that currently exists may be the outgrowth of management policies that work to the benefit of fans as well as owners.
New therapeutic targets revealed through investigations of innate immunity.

Objective: This review describes efforts to define new therapeutic targets by utilizing information derived from studies of the innate immune response to infection. These targets will provide new means to design novel therapeutics for the treatment of human disease caused by dysregulation of the innate immune response. Data Sources and Analysis: The results were derived from model systems that reflect the cellular changes accompanying activation of the innate immune system. These model systems include the use of a rabbit model of endotoxin shock that requires multiple exposures to lipopolysaccharide to induce severe pathophysiological changes that result in death. The cellular systems range from primary explants of myeloid lineage cells to stably transfected lines bearing key receptors of the innate immune system, the latter of which includes the Toll-like receptors and CD14. Studies in animal models include blocking monoclonal antibodies to rabbit CD14 and rabbit tumor necrosis factor-α. Cellular studies use measurements of cell activation as defined by activation of nuclear factor-κB, MAP kinase, and gene expression. In some studies, direct measurements of secreted cytokine levels were performed. Standard approaches to data analysis have been used. Conclusions: Evidence demonstrates the utility of anti-CD14 monoclonal antibody therapy in septic shock and the potential value of targeting intracellular kinases to modulate harmful cellular responses during sepsis. The key element to each of these approaches is to blunt, but not eliminate, the dysregulated inflammatory response that may occur in sepsis.
The influence of researcher identity on ethnographies in multiracial schools

This article explores how researchers’ social identities influence data gathered through ethnographic research in multiracial K-12 educational settings. We examine how the processes of conducting, interpreting, and analyzing ethnographic fieldwork are impacted when researchers belong to marginalized social groups. The racial and ethnic diversity among the participants at the research settings further complicated how researcher identity influenced these processes. We want to reimagine the role of the researcher of color when conducting research about and with communities of color. We suggest that researchers can act as critical participants to create opportunities for dialog about racism, sexism, and other inequities in educational settings. By doing so, we might not only improve the quality of data collected but also develop concrete ways to challenge inequities in the moment at our research sites.
Effects of calcium channel blockers on ouabain-induced oscillatory afterpotentials in organ-cultured young embryonic chick hearts.

Abstract Ouabain induces oscillatory afterpotentials (OAPs) in organ-cultured young Since increased [Ca] i resulting from an inhibition of the Na pump by ouabain triggers oscillatory movements of Ca 2+ (i.e. OAPs) intracellularly, Ca 2+ influx through the cell membrane, which tends to increase [Ca] i , may be important in developing the OAPs. Therefore, in the present experiments, effects of calcium channel blockers on ouabain-induced OAPs in organ-cultured 3 day old embryonic chick hearts were examined. Automaticity was suppressed by elevating [K] ° to 6 mM. To induce the OAPs, the preparations were stimulated (0.5 Hz) in the presence of ouabain (2.5–6.3 μM). The calcium channel blockers (10 μM) depressed the OAPs in the following order of potency: bepridil > verapamil > nifedipine > diltiazem. This order of potency of the calcium channel blockers in depressing the OAPs was the same as that for drug penetration into the cells, but different from that for depressing slow action potentials: nifedipine > diltiazem > verapamil > bepridil (our previous findings). These results suggest that an intracellular site of action of the calcium channel blockers is important for depression of the OAPs, and suppression of the slow inward Ca 2+ current cannot be the sole mechanism for suppression of the OAPs by these drugs.