cssi/SciSciGPT-SciSciNet huggingface dataset:
Visualization of transient encounter complexes in protein-protein association.

Protein–protein interactions are involved in a large number of biological processes, and though X-ray crystallography and nuclear magnetic resonance spectroscopy can be used to examine two (or more) proteins in a complex, it is difficult to establish how the two proteins interact before they form this final complex. Tang et al. have used nuclear magnetic resonance spectroscopy to directly visualize an ensemble of transient, non-specific encounter complexes for the first binary complex in the bacterial phosphotransferase system (the N-terminal domain of enzyme I and the phosphocarrier protein HPr). Of particular interest is the observation that the distribution of encounter complexes correlates with the electrostatic surface potentials on the interacting proteins. Nuclear magnetic resonance spectroscopy is used to visualize directly an ensemble of transient, non-specific 'encounter' complexes for the first binary complex in the bacterial phosphotransferase system (the N-terminal domain of enzyme I and the phosphocarrier protein HPr). An atomic probability distribution map suggests that long-range electrostatic interactions facilitate the formation of the final protein–protein complex by reducing the dimensionality of the search process. Kinetic data on a number of protein–protein associations have provided evidence for the initial formation of a pre-equilibrium encounter complex that subsequently relaxes to the final stereospecific complex1. Site-directed mutagenesis2,3,4 and brownian dynamics simulations5,6,7 have suggested that the rate of association can be modulated by perturbations in charge distribution outside the direct interaction surfaces. Furthermore, rate enhancement through non-specific binding may occur by either a reduction in dimensionality8 or the presence of a short-range, non-specific attractive potential9. Here, using paramagnetic relaxation enhancement, we directly demonstrate the existence and visualize the distribution of an ensemble of transient, non-specific encounter complexes under equilibrium conditions for a relatively weak protein–protein complex between the amino-terminal domain of enzyme I and the phosphocarrier protein HPr. Neither the stereospecific complex10 alone nor any single alternative conformation can account fully for the intermolecular paramagnetic relaxation enhancement data. Restrained rigid-body simulated annealing refinement against the paramagnetic relaxation enhancement data enables us to obtain an atomic probability distribution map of the non-specific encounter complex ensemble that qualitatively correlates with the electrostatic surface potentials on the interacting proteins. Qualitatively similar results are presented for two other protein–protein complexes.
The carbon economy of a maize crop exposed to elevated CO2 concentrations and water stress, as determined from elemental analyses

Abstract Maize crops grown in open fumigation chambers under field conditions were exposed to four levels of atmospheric CO 2 supply and two levels of water supply. Photosynthetic and respiratory activities were assessed from elemental analyses of above-ground biomass. Elemental composition varied little with CO 2 or water treatment. The mean elemental composition of organic materials per 100 g biomass at a harvest during grain filling was C 3.63 H 6.04 N 0.093 O 2.87 S 0.002 . (The balance of the mass, 2.08 g, was due to minerals). That material had more C and H and less N and was more reduced chemically than pre-anthesis biomass. While crop growth rates were affected by CO 2 and water, the growth respiration factor (0.11 g C g −1 biomass and the fraction of estimated gross photosynthesis used in growth respiration were small and unaffected by treatment. It is estimated that net carbon storage amounted to 53% of gross photosynthesis while 14% went to growth respiration and 33% went to maintenance.
The in vitro neuronal toxicity of pentraxins associated with Alzheimer's disease brain lesions

Serum amyloid P component (AP) and C-reactive protein (CRP) are normal serum components which belong to the pentraxin family of proteins. These proteins have been previously localized by immunohistochemical method to the brain lesions of Alzheimer's disease (AD). AP is a constant constituent of amyloid deposits including those found in AD. Both AP and CRP have been localized to AD neurofibrillary tangles. An indirect role for these proteins has been previously suggested in the etiology of AD. We studied the effects of serum AP and CRP on a human-derived neuronal cell line (hNT). In treated cell cultures, AP and CRP were detected immunohistochemically within hNT neurons, indicating cellular uptake of these proteins. Serum AP at the lowest serum physiological concentration (8 μg/ml) showed a marked toxicity to hNT neurons. CRP also displayed toxicity to the hNT neurons but at a level compatible with inflammatory states (50 μg/ml). These results suggest a more direct role for serum AP and CRP in the pathogenesis of AD.
Bernice Pauahi Paki and Charles Reed Bishop: A Marriage of Imperialism and Intimacy in Nineteenth-Century Hawaiʻi

As a commercial acquisition and ideal location for American settlement, Hawaii was a vulnerable kingdom during the era of Manifest Destiny. Perhaps, it was this vulnerability, which underlay King Kamehameha III’s opposition to Hawaiian women “taking up with foreigners for husbands.” In 1850 at the age of 18, Princess Bernice Pauahi Paki challenged dynastic resistance when she terminated an arranged betrothal to a royal cousin in favor of marriage to a New England entrepreneur named Charles Reed Bishop. The joining of a Native Hawaiian princess and Anglo American foreigner at a time when Hawaii was the “object of expansionist lust” offers a rare but rich opportunity to examine the interplay of ethnicity, religion, class, and gender in attitudes toward interracial marriage. Moreover, an alliance of two unequally ranked individuals in such a complicated, power-laden scenario raises crucial questions about structures of dominance. For example, are power struggles and mutual love incompatible? Placing the Bishop marriage within a comprehensible framework that considers both imperialism and intimacy, this microhistorical narrative opens to critical scrutiny the idea that the union was a love match, strategic alliance, or both romantic and diplomatic. With its incorporation of Hawaii and United States histories, this project is a provocative analysis of a single marriage as an intimate and ambiguous zone of empire. My study of the intimate is not to turn away from structures of dominance entirely, but rather to relocate possibilities for individual agency in quasi-colonial contexts.
An Application of Vector Time Series Techniques to Macroeconomic Forecasting

A wide variety of time series techniques are now used for generating forecasts of economic variables, with each technique attempting to summarize and exploit whatever regularities exist in a given data set. It appears that many researchers arbitrarily choose one of these techniques. The purpose of this article is to provide an example for which the choice of time series technique appears important; merely choosing arbitrarily among available techniques may lead to suboptimal results.
Vulnerability to ventricular fibrillation during acute coronary arterial occlusion and release

The effect of 10 minutes of occlusion, and release of occlusion, of the left anterior descending coronary artery on vulnerability to ventricular fibrillation was studied in 15 dogs. Ventricular fibrillation threshold was determined by inducing a sequence of three closely coupled extrasystoles (sequential R/T pulsing). Within 3 minutes of occlusion the current required to induce fibrillation decreased from a control value of 56 +/- 7 ma (mean +/- standard error) to 1.6 +/- 0.3 ma (P less than 0.001). It remained at this level for about 4 minutes and then rapidly returned to the control level in 8 of 10 dogs. Upon release of occlusion at 10 minutes, the ventricular fibrillation threshold was again greatly reduced; this period of reduction occurred shortly after reperfusion and was of brief duration. After both occlusion and release the duration of the ventricular vulnerable period was prolonged. The time course of change in cardiac vulnerability parallels the altered susceptibility to ventricular fibrillation after coronary arterial occlusion and release. These results recommend sequential R/T pulsing as a useful technique for probing changes in cardiac vulnerability under diverse experimental conditions.
Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer.

Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer
THE CAPITAL INVESTMENT PROJECT AS A SET OF EXCHANGE OPTIONS

Models for valuing an option to exchange one commodity for another, or any combination of n commodities for some combination of m others, are applied to the capital budgeting problem. By analyzing a project in the exchange option pricing framework, it is possible to draw wellfounded conclusions about the effects on project value of such attributes as flexibility and innovativeness. A project which uses systems that have many alternative uses is recognized by such analysis to be more valuable than an otherwise identical project which uses very specialized systems, because the former provides a greater array of choices. Likewise, a company which thinks of a new use for some kind of system will be able to generate a project which has a higher value than any other company could generate from the same system. By including divestiture as one of the alternatives in the portfolio of options representing a project, it is possible to incorporate project abandonment into the analysis, which is an improvement over earlier methodologies which simply add the value of the “abandonment option” to the discounted cash flow net present value. Finally, shortcomings of the options approach to capital budgeting are discussed.
Action of Human Plasma on the Isolated Frog Heart: Observations on Subjects with and without Essential Hypertension

Plasma samples from certain patients affect the staircase phenomenon of the frog heart. Comparison of 3 groups of subjects, normal controls, patients without essential hypertension, and patients with severe essential hypertension shows that plasmas from the last group generally abolish the staircase, whereas plasmas of the other 2 groups exhibit little or no such activity.
Experiencing disciplined software engineering at the personal level

Personal Software Process (PSP) is a new process management technique based on personal software development statistics developed at the Software Engineering Institute. This paper discusses the experiences we have gained in implementing PSP in software development and a new disciplined software engineering certificate program developed based on PSP and Capability Maturity Model (CMM).
Surface renewal and penetration models in the transient state

The transient models for some interphase transport processes have been developed based on the transient age distributions derived from the population balance. These models appear to represent physical reality more accurately than do the steady state models during the start-up period of the transport processes.
ON THE COMPOSITION AND STRUCTURE OF INDIVIDUAL GANGLIOSIDES FROM THE BRAIN OF ELASMOBRANCHES

Gangliosides with a short carbohydrate chain: II3(NeuAc)2-LacCer, II3(NeuAc)2-GgOse3Cer, II3(NeuAc)3-LacCer, II3NeuAc-LacCer, and II3NeuAC-GgOse3 Cer, were found to be predominant in the brain of 8 species of cartilaginous fish, elasmobranches. N-acetylneuraminic acid was the only sialic acid found in these gangliosides, the N-glycolyl derivative being practically absent. 4-Sphingenine was shown to be the predominant sphingoid in elasmobranch brain gangliosides. The sequential enzymatic hydrolysis of II3(NeuAc)2 -LacCer from shark and ray brain by acylneur-aminyl hydrolase (EC 3.2.1.18) and β-D-galactoside-galactohydrolase (EC 3.2.1.23), as well as permethylation studies, provide further evidence for the following structure of this major elasmobranch brain ganglioside:
The relationship between radar scattering and surface roughness of lunar volcanic features

Lunar roughness measurements derived from the Lunar Orbiter Laser Altimeter are compared to 12.6 cm wavelength radar data collected by the Miniature Radio Frequency instrument and 70 cm wavelength radar data collected by the Arecibo Observatory. These data are compared to assess how surface and subsurface roughness are correlated and affected by parameters including age and composition at length scales between 0.1 and 100 m. A range of features are analyzed including volcanic domes (Marius Hills, Rumker Hills, Gruithuisen, and Mairan Domes); mare (Imbrium, Serenitatis, and Oceanus Procellarum); pyroclastic dark mantle deposits (Sinus Aestuum, Sulpicius Gallus, and Mare Vaporum); and two young craters (Copernicus and Tycho). Statistically significant positive correlations exist between topographic roughness and both P- and S-band circular polarization ratios. The strongest correlation is observed at the longest length scales. Correlations weaken as length scales become less similar, potentially due to distinct processes controlling surface modification. Roughness is not significantly correlated with local slope. Although the Marius Hills are compositionally distinct from the Gruithuisen and Mairan domes, they are indistinguishable in roughness characteristics. Conversely, the Rumker Hills, mare, and dark mantle deposits are smoother at the length scales examined, possibly due to fine-grained mantling of regolith or pyroclastic deposits. The floor and ejecta of Tycho are the roughest surfaces measured in this study, while the floor and ejecta of Copernicus overlap the roughness distribution of the volcanic features. This study shows that many factors control the evolution of roughness over time on various length scales.
Continuous wave terahertz reflection imaging of human colorectal tissue

Continuous wave terahertz (THz) imaging has the potential to offer a safe, non-ionizing, and nondestructive medical imaging modality for delineating colorectal cancer. Fresh excisions of normal colon tissue were obtained from surgeries performed at the University of Massachusetts Medical School, Worcester. Reflection measurements of thick sections of colorectal tissues, mounted in an aluminum sample holder, were obtained for both fresh and formalin fixed tissues. The two-dimensional reflection images were acquired by using an optically pumped far-infrared molecular gas laser operating at 584 GHz with liquid Helium cooled silicon bolometer detector. Using polarizers in the experiment both co-polarized and cross-polarized remittance form the samples was collected. Analysis of the images showed the importance of understanding the effects of formalin fixation while determining reflectance level of tissue response. The resulting co- and cross-polarized images of both normal and formalin fixed tissues showed uniform terahertz response over the entire sample area. Initial measurements indicated a co-polarized reflectance of 16%, and a cross-polarized reflectance of 0.55% from fresh excisions of normal colonic tissues.
Aspirin for Primary Prevention: A Challenging Decision

Aspirin for primary prevention of cardiovascular disease (CVD) remains a challenging issue for clinicians, patients, and health policy makers. Even with the availability of multiple randomized trials and several high-quality systematic reviews and meta-analyses, significant debate remains about
Prostate Specific Membrane Antigen-Based Therapeutics

Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with 177Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.
Wave dynamics in mantle plume heads and hotspot swells

Laboratory experiments with thermal plumes in fluid with temperature-dependent viscosity suggest that wave-like instabilities can form in the horizontally flowing, disk-shaped head of the plume. The waves propagate radially outward from the axis of the plume and appear to be most intense in a finite band near the perimeter of the plume head. A simple theoretical model shows that interfacial waves in a highly viscous fluid may occur if the plume-head is comprised of temperature-dependent-viscosity fluid that cools as it flows between two boundaries. The model suggests that the waves arise as an oscillatory instability and that wave formation is most robust in the colder regions of the plume-head, as indicated by the experiments. The theory also predicts that the instability will only occur above some critical plume-head flow velocity, and that mantle plume conditions are generally supercritical.
Specific oral tolerance induction (SOTI) in pediatric age: clinical research or just routine practice?

Miceli Sopo S, Onesimo R, Giorgio V, Fundaro C. Specific oral tolerance induction (SOTI) in pediatric age: Clinical research or just routine practice? Pediatr Allergy Immunol 2010: 21: e446–e449. © 2009 John Wiley & Sons A/S Specific Oral Tolerance (SOTI) is a promising therapy of food allergy, specially for IgE-mediated cow milk allergy (CMA) in pediatric age. Randomized controlled trials have reported that about 35% of children, at least 5 years of age, became full tolerant to cow milk proteins after SOTI. Regard to the safety, literature describes about 200 children who underwent SOTI, with no fatal events. Nevertheless, a considerable percentage of those children (15%–20%) had to stop SOTI, because of important adverse effects. Numerous protocols have been described, some audacious and other prudent, however all demand an intense commitment either of the doctors and of the families. The information about the follow up of the children who underwent SOTI are still insufficient. For these reasons, we think that SOTI is still an experimental therapy.
Modeling of Multiarticular Muscles: Importance of Inclusion of Tendon–Pulley Interactions in the Finger

The purpose of this study was to examine force transmission from one of the major multi-articular muscles of the finger, flexor digitorum pro-fundus (FDP), to the index finger. Specifically, we examined whether the popular moment arm (MA)-joint torque technique of modeling muscle force transmission can accurately represent the effects of the FDP on finger movement. A dynamic finger model employing geometric MA values (model I) was compared with another model including realistic tendon force transformation mechanisms via pulley structures and joint reaction forces (model II). Finger flexion movements generated by these models were compared with those obtained from in vivo stimulation experiments. The model with the force transformation mechanisms (model II) resulted in more realistic joint spatial coordination (i.e., proximal interphalangeal > metacarpophalangeal ges distal interphalangeal) than the MA-based model (model I) in relation to the movement patterns evoked by stimulation. Also, the importance of the pulley structures and passive joint characteristics was confirmed in the model simulation; altering/eliminating these components significantly changed the spatial coordination of the joint angles during the resulting movements. The results of this study emphasize the functional importance of the force transformation through various biomechanical components, and suggest the importance of including these components when investigating finger motor control, such as for examining injury mechanisms or designing rehabilitation protocols.
Worldwide assessments of laser radar tactical scenario performance variability for diverse low altitude atmospheric conditions at 1.0642 μm and 1.557 μm

Spatial, spectral and temporal variations in operating conditions are major contributors to the expected variability/uncertainty in system performance. The ratio of signal-to-noise ratio (SNR) based on climatological data to a standard atmosphere is the primary performance metric used, with results presented in the form of histograms and maps of worldwide LADAR performance variation. This metric is assessed at 2 wavelengths, 1.0642 µm and 1.557 µm, for a number of widely dispersed land and maritime locations worldwide over oblique and vertical air to surface paths in which anticipated clear air aerosols and location specific heavy rain and 150 m thick fog occur. Seasonal, boundary layer, and time of day variations for a range of relative humidity percentiles are also considered. In addition to realistic vertical profiles of molecular and aerosol extinction, air-to-ground cloud free line of sight (CFLOS) probabilities as a function of location for this geometry are computed. Observations from the current study strongly indicate that use of the standard atmosphere to predict performance will produce overly optimistic, in many cases extremely so, estimates of expected performance. Locally heavy rain, when present, severely limits LADAR system performance at these wavelengths. Some operational capability exists for vertical looks through fog.
Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization

Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Background. Nephrotic syndrome is a common kidney dis- ease in both children and adults that is characterized by dra- matic structural changes in the actin-rich foot processes of glomerular podocytes. Although glucocorticoids are the pri- mary treatment for nephrotic syndrome, neither the target cell nor mechanism of action of glucocorticoids in nephrotic syn- drome is known. For the last 30 years glucocorticoids have been presumed to act by reducing the release of soluble mediators of disease by circulating lymphocytes. In contrast, we hypothesized that glucocorticoids exert their beneficial effects in nephrotic syndrome by direct action on podocytes. Methods. Cultured murine podocytes were treated with glu- cocorticoids in the presence and absence of mifepristone (to inhibit glucocorticoid-induced transcriptional activation) and challenged using our previously reported in vitro model of puromycin aminonucleoside (PAN)-induced podocyte injury, as well as by direct disruption of actin filaments with latrun- culin and cytochalasin. Cell viability, actin filament distribution, total polymerized actin content, and actin-regulating guanine triphosphatase (GTPase) activities were measured. Results. We demonstrated that treatment of cultured murine podocytes with the glucocorticoid dexamethasone both pro- tected and enhanced recovery from PAN-induced injury. Dexamethasone also increased total cellular polymerized actin, stabilized actin filaments against disruption by PAN, latrunculin, or cytochalasin, and induced a significant increase in the activity of the actin-regulating GTPase RhoA. Conclusion. These data suggest that, contrary to the current therapeutic paradigm, the beneficial effects of glucocorticoids in nephrotic syndrome may result, at least in part, from direct effects on podocytes leading to enhanced actin filament stability.
Digital learning, digital scholarship and design thinking

This paper identifies opportunities for design thinking to be integrated into digital learning and digital scholarship initiatives. The paper traces how the rise of digital culture has led to the reconsideration of models for learning and the call for new modes of knowledge production, spearheaded by an array of fields from writing programs to computer science. Drawing upon case studies from new media education and the digital humanities, the paper argues that design thinking that is situated, interpretive, and user-oriented is well suited to these initiatives. The paper concludes with a call for design thinking research to engage with emerging models for learning and knowledge production, work whose effects could be felt at an epistemic level for generations.
USE of ORGANIC SOLVENTS FOR IMPROVING PEELABILITY of TOMATOES

A prepeeling dip was used to demonstrate that removal or modification of the cuticular waxes from the tomato fruit could be used to improve the tomato peeling process. The tomatoes were dipped at various temperatures for 1 mi. prior to regular lye peeling. The optimum temperature was found to be 45C. Several organic solvents including chloroform, ethyl dcetate, ketones, and alcohols were used. These tomatoes were compared to tomatoes peeled using the lye without the dip. The prepeeling dip reduced the thickness of the cuticular wax layer and produced cracks in the cutin surface. This facilitated good penetration of lye into the tomato resulting in more complete peeling. Peeling after pretreatment produced 86% well peeled tomatoes as compared to 33% well peeled in the control run.
Scaling of decoherence for a system of uncoupled spin qubits

Significant experimental progresses in recent years have generated continued interest in quantum computation. A practical quantum computer would employ thousands if not millions of coherent qubits, and maintaining coherence in such a large system would be imperative for its utility. As an attempt at understanding the quantum coherence of multiple qubits, here we study decoherence of a multi-spin-qubit state under the influence of hyperfine interaction, and clearly demonstrate that the state structure is crucial to the scaling behavior of n-spin decoherence. Specifically, we find that coherence times of a multi-spin state at most scale with the number of qubits n as √n, while some states with higher symmetries have scale-free coherence with respect to n. Statistically, convergence to these scaling behavior is generally determined by the size of the Hilbert space m, which is usually much larger than n (up to an exponential function of n), so that convergence rate is very fast as we increase the number of qubits. Our results can be extended to other decoherence mechanisms, including in the presence of dynamical decoupling, which allow meaningful discussions on the scalability of spin-based quantum coherent technology.
How future mobility meets IT: Cyber-physical system designs revisit semiconductor technology

Cyber-Physical System (CPS) exemplified by future mobility application systems necessitates unconventional embedded design considerations in embedded systems; multiples latency-aware computing and communication construction, the importance of once non-functional requirements like security and safety to cover physical- and cyber-systems, and VLSI life-time design by ecology. All in all we have to reexamine and re-organize current semiconductor technology to produce platform bases for connected open collaborations to tackle global human challenges.
Large Scale Policy Making

Challenging pluralist theory and the incremental model of policy making, Paul Schulman argues that many public policy undertakings may fail because of critical mismatches between the scale requirements of an objective and the political and organizational resources actually applied to its pursuit. At the same time, the book explores some of the special risks and hazards associated with large-scale policy frameworks.
Actinide Speciation in Spent Fuel Leaching Studies

The uranium and plutonium chemistry relevant for spent fuel leach studies is discussed. Model calculations are evaluated by comparison with the results of spent UO2 fuel leaching obtained in the Swedish SKB program. The thermodynamic data were found to agree sufficiently with the measured solution concentrations that it can be assumed that in oxic natural waters, leachate uranium from spent fuel would be uranyl carbonate complexes in the solution (or hydroxo complexes in the absence of carbonate) while schoepite would be the solubility limiting solid. For plutonium, PuO2+ would be the solution species and Pu(OH)4 the solubility limiting solid.
The effect of do-not-resuscitate orders on length of stay.

In 1988, a new do-not-resuscitate policy aimed at assisting professional staff, nurses, patients, and families in end-of-life choices replaced the existing policy at The Cleveland Clinic Foundation. We conducted a retrospective chart review to examine the effects of the new policy on length of stay. Data were collected on demographics, clinical information, length of stay, and the frequency of do-not-resuscitate orders for expired Medicare patients in 1987 (n=125) and 1989 (n=135). Length of stay for patients who received a do-not-resuscitate order was significantly reduced in 1989 compared with 1987, partly because the orders were issued earlier in patients’ stays in 1989. The number of days from writing the order until death did not change significantly from 1987 to 1989. We conclude that a well-defined do-not-resuscitate policy can reduce length of stay.
Excess Burden of Taxation

The excess burden of taxation is the efficiency cost, or deadweight loss, associated with taxation. Excess burden is commonly measured by the area of the associated Harberger triangle, though accurate measurement requires the use of compensated demand and supply schedules. The generation of empirical excess burden studies that followed Arnold Harberger’s pioneering work in the 1960s measured the costs of tax distortions to labor supply, saving, capital allocation, and other economic decisions. More recent work estimates excess burdens based on the effects of taxation on more comprehensive measures of taxable income, reporting sizable excess burdens of existing taxes. JEL Classifications: H21, D61. James R. Hines Jr. Department of Economics University of Michigan 343 Lorch Hall 611 Tappan Street Ann Arbor, MI 48109-1220
Subsurface Transport of Cryptosporidium in Soils of Wisconsin's Carbonate Aquifer Region

is a waterborne pathogen known to have a significant reservoir in bovine manure. Land-dependent manure disposal may not result in significant or reliable pathogen attenuation and, therefore, presents a risk for transport of pathogenic spp. to groundwater. One factor missing in the existing literature is the role soil characteristics play in affecting oocyst transport. Of specific concern in regions with carbonate geology are macropores and other soil structures that contribute to preferential flow. Therefore, research is needed to understand soil type effects and important transport pathways for pathogens such as oocysts to drinking water wells. This study investigated transport potential in several soils overlying Wisconsin's vulnerable carbonate aquifer and related the soil transport to soil series and textural class. Experimental work involved monitoring the transport of oocysts through intact soil columns of different soil series under simulated rain conditions. Results demonstrate that a significant portion of oocysts will sorb or be physically entrapped in the soil, especially in soil with high clay content. However, silt loam soils with comparatively lower clay content demonstrated an ability to transport oocysts through the soil profile primarily via the first flush of water infiltrating through soil macropores. The rate of oocyst migration in silt loam soils paralleled the bromide tracer front, thus bypassing the soils' ability to strain or adsorb oocysts out of infiltrating water. Nevertheless, proper manure treatment and management are necessary to minimize public health risks.
Aldehyde dehydrogenase 2 activation and coevolution of its εPKC-mediated phosphorylation sites

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a key enzyme for the metabolism of many toxic aldehydes such as acetaldehyde, derived from alcohol drinking, and 4HNE, an oxidative stress-derived lipid peroxidation aldehyde. Post-translational enhancement of ALDH2 activity can be achieved by serine/threonine phosphorylation by epsilon protein kinase C (ePKC). Elevated ALDH2 is beneficial in reducing injury following myocardial infarction, stroke and other oxidative stress and aldehyde toxicity-related diseases. We have previously identified three ePKC phosphorylation sites, threonine 185 (T185), serine 279 (S279) and threonine 412 (T412), on ALDH2. Here we further characterized the role and contribution of each phosphorylation site to the enhancement of enzymatic activity by ePKC. Each individual phosphorylation site was mutated to a negatively charged amino acid, glutamate, to mimic a phosphorylation, or to a non-phosphorylatable amino acid, alanine. ALDH2 enzyme activities and protection against 4HNE inactivation were measured in the presence or absence of ePKC phosphorylation in vitro. Coevolution of ALDH2 and its ePKC phosphorylation sites was delineated by multiple sequence alignments among a diverse range of species and within the ALDH multigene family. We identified S279 as a critical ePKC phosphorylation site in the activation of ALDH2. The critical catalytic site, cysteine 302 (C302) of ALDH2 is susceptible to adduct formation by reactive aldehyde, 4HNE, which readily renders the enzyme inactive. We show that phosphomimetic mutations of T185E, S279E and T412E confer protection of ALDH2 against 4HNE-induced inactivation, indicating that phosphorylation on these three sites by ePKC likely also protects the enzyme against reactive aldehydes. Finally, we demonstrate that the three ALDH2 phosphorylation sites co-evolved with ePKC over a wide range of species. Alignment of 18 human ALDH isozymes, indicates that T185 and S279 are unique ALDH2, ePKC specific phosphorylation sites, while T412 is found in other ALDH isozymes. We further identified three highly conserved serine/threonine residues (T384, T433 and S471) in all 18 ALDH isozymes that may play an important phosphorylation-mediated regulatory role in this important family of detoxifying enzymes. ePKC phosphorylation and its coevolution with ALDH2 play an important role in the regulation and protection of ALDH2 enzyme activity.
The Use of “Omics” to Guide the Selection of Targeted Therapy

In this book, the role of many different proteins, pathways, or genetic events in affecting the function of leukemic cells, as well as their suitability for therapeutic modulation, is discussed. However, since acute myeloid leukemia (AML) is a very heterogeneous disease, it will be necessary to match the characteristics of individual patients to the selection of the right targeted agent in order to maximize efficacy. In this chapter, we discuss how the application of the numerous molecular profiling arrays that are now available can be utilized to provide the answer to this dilemma. The development of methods to combine data from multiple arrays, termed “integromics” will enable a more sophisticated application of “omic” data that will facilitate the selection of combinations of targeted agents on an individualized basis.
Governing institutions, ideologies, and gender: Toward the possibility of equal political representation

U.S. governing institutions, especially Congress, have received limited investigation as gendered institutions. Political representation suffers as a result. Improved theorizing about gender and governing institutions requires discursive shifts. A framework to improve empirical research is advanced. It juxtaposes variants of gender proto-ideologies, masculinism and feminalism, and organizes these pairs according to strands of shared views. These gender strands also compound with the spectrum of governing ideologies, such as social liberalism or neoconservatism. This approach enables nuanced interpretation and explanation, pointing toward potential alliances and sites of transformation for better political representation.
Implementing Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) With Preteen Children Displaying Problematic Sexual Behavior

Abstract Problematic sexual behavior (PSB) is a fairly common presenting concern among preteen children with histories of trauma. Unfortunately, relatively little information about these concerns are provided in training programs and clinicians often report lacking the skills and confidence to intervene when PSB is present. Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), on the other hand, is a well-known and well-validated intervention for children who experienced maltreatment and trauma. Current evidence-based treatment techniques for PSB are primarily cognitive-behavioral in nature and easily delivered within the standard TF-CBT protocol. This paper reviews the empirical and theoretical premises of evidence-based treatment techniques for PSB and discusses how the clinician can implement them within the context of TF-CBT, while maintaining fidelity to the TF-CBT protocol. Conducting an assessment to determine the appropriateness of this form of treatment is examined as well as recommendations on addressing safety issues that may be identified during assessment.
Trimethylamine-N-Oxide Instigates NLRP3 Inflammasome Activation and Endothelial Dysfunction.

Background/Aim: Plasma trimethylamine-N-oxide (TMAO), a product of intestinal microbial metabolism of dietary phosphatidylcholine has been recently associated with atherosclerosis and increased risk of cardiovascular diseases (CVD) in rodents and humans. However, the molecular mechanisms of how TMAO induces atherosclerosis and CVD progression are still unclear. The present study tested whether TMAO induces NLRP3 inflammasome formation and activation and thereby contributes to endothelial injury initiating atherogenesis. Methods: Inflammasome formation and activation was determined by confocal microscopy, caspase-1 activity was measured by colorimetric assay, IL-1β production was measured using ELISA, cell permeability was determined by microplate reader and ZO-1 expression was determined by western blot analysis and confocal microscopy. In in vivo experiments, TMAO was infused by osmotic pump implantation. Results: TMAO treatment significantly increased the colocalization of NLRP3 with Asc or NLRP3 with caspase-1, caspase-1 activity, IL-1β production, cell permeability in carotid artery endothelial cells (CAECs) compared to control cells. Pretreatment with caspase-1 inhibitor, WEHD or Nlrp3 siRNA abolished the TMAO-induced inflammasome formation, activation and cell permeability in these cells. In addition, we explored the mechanisms by which TMAO activates NLRP3 inflammasomes. TMAO-induced the activation of NLRP3 inflammasomes was associated with both redox regulation and lysosomal dysfunction. In animal experiments, direct infusion of TMAO in mice with partially ligated carotid artery were found to have increased NLRP3 inflammasome formation and IL-1β production in the intima of wild type mice. Conclusion: The formation and activation of NLRP3 inflammasomes by TMAO may be an important initiating mechanism to turn on the endothelial inflammatory response leading to endothelial dysfunction.
Preeclampsia knowledge among women in Utah.

BACKGROUND Despite the benefits of preeclampsia (PE) education in improving health outcomes, little is known about how often healthcare providers in Utah include PE in prenatal education or how much information women retain. As such, the purpose of this study was to explore PE awareness among mothers in Utah and inquire how often PE is included in prenatal education. Factors associated with PE knowledge were also investigated. METHODS A cross-sectional survey was conducted. Questions were created from two Preeclampsia Awareness Surveys developed by the Preeclampsia Foundation. PE knowledge was measured with 29 items from the 2014 Preeclampsia Awareness Survey, and a knowledge score was calculated. RESULTS A total of 340 women completed the survey. Over half (56.7%) of women reported their healthcare provider described the signs and symptoms of PE to them. The mean PE knowledge score was 17.07. Hearing of PE from a healthcare provider, having the signs and symptoms of PE described by a healthcare provider and having a history of PE were significantly associated with a higher PE knowledge score. CONCLUSIONS Patient awareness is essential to the successful management of PE. The need for improved PE education in Utah was evident in this survey. As not all healthcare providers are diligent in instructing patients regarding PE, more research is needed to fully assess the knowledge of mothers and examine the practices of providers. An explanation of PE signs and symptoms should be given to all women at prenatal care visits to improve health outcomes.
Hepatic vascular diseases

Abstract Hepatic vascular diseases often present with non-specific and subtle histologic changes that could be easily overlooked during the evaluation of liver biopsies and surgical material. A liver biopsy typically samples small vasculature and thus is not a sensitive tool to evaluate the histopathology of large blood vessels. Vascular disease is rarely clinically suggested in the differential diagnosis of a case, and the indication for the liver biopsy is usually "elevated liver enzymes" or "cirrhosis". Hence, when evaluating liver diseases, pathologists may overlook subtle histopathologic changes associated with vascular disease and instead focus on hepatitis, biliary disease or cirrhosis. Pathologists evaluating liver biopsies should be familiar with vascular diseases and their clinical implications. Recognizing hepatic vascular disorders is critical in order to trigger appropriate medical management. This review provides a brief overview of relatively common hepatic vascular diseases that surgical pathologists may encounter in practice.
Duplicitous Freedom: Moral and Material Care Work in Anti-Trafficking Rescue and Rehabilitation:

Contemporary anti-trafficking narratives exemplify the centrality of family unaccountability as one of the root causes of sex trafficking. Suggesting that human trafficking can be explained by bad ...
Congenital Esophageal Pathology

Congenital esophageal stenosis is an intrinsic stenosis of the esophagus, present at birth, which is caused by congenital malformation of the esophageal wall architecture. Three forms of congenital esophageal stenosis exist: a membranous web or diaphragm occluding the esophageal lumen, fibromuscular hypertrophy of the esophageal wall, and tracheobronchial remnants embedded in the esophageal wall (Nihoul-Fekete et al., Pediatr Surg Int 2:86–92, 1987). The membranous web or diaphragm, the rarest of the three forms, consists of a partially obstructing lesion with an eccentric opening covered on both sides with squamous epithelium. These are located in the mid to distal esophagus. Stenosis due to fibromuscular hypertrophy exhibits normal squamous epithelium overlying a proliferation of smooth muscle fibers and fibrous connective tissue similar to that seen in hypertrophic pyloric stenosis, leading to narrowing in the mid to distal esophagus. This tapering is more gradual than the narrowing seen with tracheobronchial remnants. Tracheobronchial remnants, the most common congenital esophageal stenosis, results from abnormal separation of the esophagus and tracheobronchial tree during embryologic development resulting in cartilaginous remnants ectopically located in the esophageal wall. The narrowing occurs in the distal esophagus, is covered by normal mucosa, and is often abrupt in appearance due to a ring of cartilage in the esophageal wall. The cartilaginous remnants may or may not form a complete ring.
Myocardial acidosis and the mitigation of tissue ATP depletion in ischemic cardiac muscle: the role of the mitochondrial ATPase.

A number of reports have now appeared demonstrating a marked inhibition of the mitochondrial oligomycin-sensitive ATPase as the result of the interruption of blood flow (ischemia) in a number of tissues including liver,1,2 kidney,3,4 skeletal muscle5 and cardiac muscle.6–9 By and large, the ATPase inhibition observed in ischemic tissues appears to be reversible if blood flow is resumed early enough,2,4,6,9 suggesting that this inhibition represents a regulatory response of the oligomycin-sensitive ATPase complex to one or more metabolic alterations within the ischemic cells.
Calcium Transport Inhibition, Stimulation, and Light Dependent Modulation of the Skeletal Calcium Release Channel (RyR1) by the Prototropic Forms of Pelargonidin

The principle calcium regulator in the muscle cell is the calcium ion release channel (RyR). Improper calcium homeostasis in the muscle cell is the foundation of many pathological states and has been targeted as a contributing factor to ventricular tachycardia, which is known to precede sudden cardiac arrest. Numerous endogenous and exogenous compounds can affect the way RyR regulates calcium. In this study the anthocyanidin Pelargonidin (Pg), an important natural colorant and dietary antioxidant, is evaluated for its effect on regulating the transport of calcium through the RyR1 of skeletal muscle sarcoplasmic reticulum. Pelargonidin undergoes time dependent structural changes in aqueous solutions at physiological pH and a mixture of up to seven forms of Pelargonidin are present in solution simultaneously. Pelargonidin is a unique RyR1 modulator. It can both stimulate and inhibit the RyR1 depending on the experimental conditions. In addition, when Pelargonidin is irradiated with white light, its inhibition properties on the RyR1 are essentially nullified. Proposed mechanisms include excited state charge shift within RyR1-Pg complexes.
Cytokines, Signal Transduction, and Inflammatory Demyelination: Review and Hypothesis

The mechanism of focal demyelination in multiple sclerosis has been a long-standing enigma of this disorder. Cytokines, a diverse family of signalling molecules, are viewed as potential mediators of the process based on clinical observations and studies with animal models and tissue/cell culture systems. Myelin and oligodendrocyte (OL) destruction occur in cultured preparations subjected to cytokines such as tumor necrosis factor-α (TNFα) and lymphotoxin (LT). Many studies have shown these and other cytokines to be elevated at lesion sites and in the CSF of multiple sclerosis (MS) patients, with similar findings in animal models. Some variability in the nature of MS lesion formation has been reported, both OLs and myelin being primary targets. To account for myelin destruction in the presence of apparently functional OLs we hypothesize that cytokines such as TNFα and LTα contribute to myelin damage through triggering of specific reactions within the myelin sheath. We further propose that neutral sphingomyelinase (SMase) is one such enzyme, two forms of which have been detected in purified myelin. An additional event is accumulation of cholesterol ester, apparently a downstream consequence of cytokine-induced SMase. The resulting lipid changes are viewed as potentially destabilizing to myelin, which may render it more vulnerable to attack by invading and resident phagocytes.