cssi/SciSciGPT-SciSciNet huggingface dataset:
Alcohol in excess: CRF1 receptors in the rat and mouse VTA and DRN

Manipulation of the stress neuropeptide corticotropin-releasing factor (CRF), specifically central antagonism of the type 1 receptors (CRF-R1), effectively reduces alcoholic-like ethanol drinking in rodents. Escalated consumption is largely controlled by neurocircuitry that is important for reward and affect, such as the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN). The current studies investigated the role of CRF-R1 within the VTA and DRN and their relation to escalated ethanol drinking in two species. An additional goal was to explore whether high alcohol-drinking individuals would be more affected by CRF-R1 antagonism than low alcohol-drinking individuals. With a two-bottle choice drinking procedure, adult male C57BL/6J mice and Long–Evans rats were given 24-h access to 20 % ethanol and water on an intermittent schedule. Rats and mice were implanted with cannulae targeting the VTA or DRN. Doses of the CRF-R1 antagonist CP-154,526 (butyl-[2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine)) were microinfused to modulate drinking of ethanol and water over the course of 24 h. In both mice and rats, intra-VTA CP-154,526 selectively decreased ethanol intake, while identical doses (0.3 and 0.6 μg) infused intra-DRN reduced both ethanol and water drinking. Long–Evans rats displayed a range of individual differences for ethanol preference, and CP-154,526 suppressed ethanol drinking in the high-preferring animals regardless of brain site manipulation. The current findings confirm previous studies that blockade of CRF-R1 efficaciously reduces escalated drinking while also suggesting that the effects of intermittent access on alcohol consumption may require CRF interaction with dopamine in the VTA.
Estimation of above-ground forest biomass using metrics based on Gaussian decomposition of waveform lidar data

Large-footprint waveform light detection and ranging lidar data have been widely used in above-ground forest biomass estimation. Waveform metrics derived from basic statistics e.g. percentile of energy of the lidar waveform, such as canopy height and height of median energy, have been applied to biomass estimation in numerous studies. In this study, a set of metrics based on Gaussian decomposition GD results were developed and evaluated for forest above-ground biomass estimation using NASA’s laser vegetation imaging sensor LVIS data. The GD metrics were designed to explicitly incorporate lidar intensity and vertical structures of canopy layers for biomass estimation. The proposed GD metrics used information related to the above-ground height of each Gaussian centroid and the Gaussian area index GAI, where GAI is the area covered by a Gaussian function. Two types of novel GD metrics were developed: 1 percentile-height GAI metrics expressing the GAI summation of a subset of Gaussian centroids located within a certain percentile height range; and 2 height-weighted GAI metrics, a summation of GAIs of a waveform weighted by the corresponding heights of their Gaussian centroids. A biomass regression model was built by eight newly developed GD metrics using GAI information and five pre-existing GD-derived metrics that have not previously been used for biomass estimation. The performance of the regression model was then compared to another regression model using 12 previously published metrics non-GD metrics. The Random Forests RF regression algorithm was employed for predicting biomass. The RF out-of-bag results indicated that above-ground biomass estimations using GD metrics achieved significantly better results than those derived from non-GD metrics for deciduous plots 19% lower root mean square error RMSE, 25% higher coefficient of determination R2, and marginally better results in coniferous plots 4% lower RSME, 6% higher R2. The combination of GD and non-GD metrics achieved comparable biomass estimation results to the model using exclusively GD metrics. GD metrics also showed strong correlation with forest attributes such as mean diameter at breast height DBH and stem density. This study contributes to the usage of GD results for accurate estimation of forest above-ground biomass in large-footprint lidar waveform data in temperate deciduous forests, because temperate deciduous forests have been proved challenging in regard to lidar-derived biomass estimations.
Carbon Nanotube Array Thermal Interfaces on Chemical Vapor Deposited Diamond

Carbon nanotube (CNT) arrays have been directly synthesized on plasma-enhanced chemical vapor deposited diamond films in the same growth chamber. The diamond films were grown using a bias-enhanced nucleation technique that produces relatively smooth and flat films. The thermal resistances of the CNT array/diamond film interface were measured using a photoacoustic technique to be approximately 12 mm2 ·K/W at moderate pressures.Copyright © 2007 by ASME
An effective medium method for calculation of the T matrix of aggregated spheres

Abstract An effective medium approach is developed for describing the radiative scattering characteristics of large-scale clusters of spheres. The formulation assumes that the waves exciting each sphere in the cluster can be described by a regular vector harmonic expansion, centered about a common origin of the cluster, and characterized by an effective propagation constant mek. By combining this description with the multiple sphere interaction equations a ‘homogeneous’ T matrix of the cluster is derived, which is analogous to using the effective propagation constant models of the Varadans in conjunction with Waterman's EBCM. However, it is shown that the homogeneous T matrix will not automatically satisfy energy conservation because it cannot account for dependent scattering effects among the spheres. A ‘discrete’ formulation of the T matrix is then developed which retains the effective medium description of the exciting field yet provides for energy conservation. Illustrative calculations show that the effective medium T matrix can provide accurate predictions of the cross sections and scattering matrices of clusters containing a large number of uniformly packed spheres, yet this approximation uses a fraction of the computational time required for an exact solution.
Complications of diuretic therapy: Severe alkalosis and syndrome resembling inappropriate secretion of antidiuretic hormone

Abstract Two patients with benign illnesses who developed life-threatening complications from therapy with ethacrynic acid (Case 1) and furosemide (Case 2) are described. Case 1 presented in a semi-comatose state with severe alkalosis (pH 7.70) on a daily dose of 50 to 100 mg. of ethacrynic acid. Case II presented with marked hyponatremia (sodium, 112 mEq./L.) associated with a normal BUN (10 mg.%), a concentrated urine (600 mOsm/Kg. H 2 O) and high urinary sodium concentration (60 mEq./L.). This combination initially suggested the syndrome of inappropriate secretion of antidiuretic hormone. However, the latter diagnosis was excluded by the correction of the hyponatremia with saline infusion and the history of furosemide ingestion. Case 2 had developed recurrent severe hyponatremia during a two year period while on furosemide therapy. Hyponatremia (130 mEq./L.) recurred during a controlled therapeutic trial with furosemide (20 mg. daily) in the hospital. This hyponatremia resulted in part from water retention which appeared to occur in response to the initial acute volume contraction produced by a single dose of the diuretic in this patient. This initial volume contraction was presumably a stimulus for antidiuretic hormone secretion. The possible mechanisms for the development of severe alkalosis and hyponatremia with these agents are discussed. The need for determination of individual responsiveness to these agents and for careful monitoring of serum electrolytes subsequently is emphasized.
Metastable phase formation in thin film reactions

Abstract The phenomenon of metastable phase formation during a constant temperature and constant pressure thin film reaction is explained by a kinetic model emphasizing the rate of transition. It is assumed that the reaction obeys a maximum time-dependent rather than time-independent negative free energy change. The product persists in the metastable state due to a high activation barrier to later transition.
A Systematic Framework for the Development and Analysis of Signed Digraphs for Chemical Processes. 1. Algorithms and Analysis

In the recent past, graph-based approaches have been proposed by various researchers for safety analysis and fault diagnosis of chemical process systems. Though these approaches have shown promise, there are a number of important issues that have not been adequately addressed in the literature. The issue of systematic development of graph representations for chemical processes has not been addressed in the literature. This is an important issue because the development of digraphs is error-prone and time-consuming. Further, little attention has been paid toward understanding the conceptual relationship between the underlying mathematical description and the analysis procedures for the graph model. Also, the utility of these graph-based approaches at a flowsheet level has not been studied. With these issues in perspective, in this first part of the two-part paper, we focus on the systematic development of graph models and the conceptual relationship between the analysis of graph models and the underlying ma...
A Knowledge Management Success Model: Theoretical Development and Empirical Validation

We examine a knowledge management (KM) success model that incorporates the quality of available knowledge and KM systems built to share and reuse knowledge such as determinants of users' perception of usefulness and user satisfaction with an organization's KM practices. Perceived usefulness and user satisfaction, in turn, affect knowledge use, which in our model is a measure of how well knowledge sharing and reuse activities are internalized by an organization. Our model includes organizational support structure as a contributing factor to the success of KM system implementation. Data collected from 150 knowledge workers from a variety of organizations confirmed 10 of 13 hypothesized relationships. Notably, the organizational support factors of leadership commitment, supervisor and coworker support, as well as incentives, directly or indirectly supported shared knowledge quality and knowledge use. In line with the proposed model, the study lends support to the argument that, in addition to KM systems quality, firms must pay careful attention to championing and goal setting as well as designing adequate reward systems for the ultimate success of these efforts. This is one of the first studies that encompasses both the supply (knowledge contribution) and demand (knowledge reuse) sides of KM in the same model. It provides more than anecdotal evidence of factors that determine successful KM system implementations. Unlike earlier studies that only deal with knowledge-sharing incentives or quality of shared knowledge, we present and empirically validate an integrated model that includes knowledge sharing and knowledge quality and their links to the desired outcome-namely, knowledge reuse.
Are "negative bursts" due to absorption?

Optical activity near the time of two microwave negative bursts is distinctive enough to demonstrate a real relation, but does not occur simultaneously with the radio events. Such a loose association between microwave flux decreases and Hα prominence or filament activity is typical of a sample of 23 negative bursts. A model of a microwave occulting cloud differs from that of an Hα absorber: the Hα dark flocculus is relatively low, dense, and compact; the microwave occulter is higher in the corona, larger, and more completely ionized. The two types of absorption are not expected to be seen simultaneously, although they could be separate phases of an ejection of chromospheric material into the corona. The association of microwave decreases with Hα activity in some cases, and their usual non-simultaneity, is consistent with interpretation of the decrease as absorption, but it does not rule out alternative interpretations such as an intrinsic change in the emission of the microwave source. The location of decrease-associated activity has a suggestive, though not statistically significant, bias toward east limb that leads one toward an absorption interpretation, with asymmetry introduced by a tendency for ejected material to move from the leading part of an active region toward the following part, agreeing with Liszka's observation of asymmetry in the line-of-sight velocities of prominences.
Structure, Function, and Biology of the Enterococcus faecalis Cytolysin

Enterococcus faecalis is a Gram-positive commensal member of the gut microbiota of a wide range of organisms. With the advent of antibiotic therapy, it has emerged as a multidrug resistant, hospital-acquired pathogen. Highly virulent strains of E. faecalis express a pore-forming exotoxin, called cytolysin, which lyses both bacterial and eukaryotic cells in response to quorum signals. Originally described in the 1930s, the cytolysin is a member of a large class of lanthionine-containing bacteriocins produced by Gram-positive bacteria. While the cytolysin shares some core features with other lantibiotics, it possesses unique characteristics as well. The current understanding of cytolysin biosynthesis, structure/function relationships, and contribution to the biology of E. faecalis are reviewed, and opportunities for using emerging technologies to advance this understanding are discussed.
Forest mapping with a generalized classifier and Landsat TM data

Monitoring landcover and landcover change at regional and global scales often requires Landsat data to identify and map landscape features and patterns with sufficient detail. Analytical methods based on image-by-image interpretation are too time-consuming and labor-intensive for studies of large areas to be undertaken with any degree of frequency. One potential solution is to develop algorithms or classifiers that can be generalized beyond the arena of the initial training to new images from different spatial, temporal or sensor domains. Building upon earlier success with a generalized classifier to monitor forest change, we now address the question of generalization for classifications of stable landcovers. We evaluate the ability of a supervised neural network, Fuzzy ARTMAP, to identify conifer forest across time and space with Landsat Thematic Mapper (TM) images for a region in northwest Oregon. We also assess the effects of atmospheric corrections on generalized classification accuracies. Using midsummer images atmospherically corrected with a simple dark-object-subtraction (DOS) method, there is no statistically significant loss of accuracy as the classification is extended from the initial training image to other images from the same scene (path and row): temporal generalization is successful. Extending the classifier across space and time to nearby scenes results in a mean decline of 8–13% accuracy depending on the atmospheric correction used. Obvious sources of error, such as seasonality, solar angle variation, and complexity of landcover identification, do not explain the decline in error. Additionally, the patterns in generalization accuracies are complex, and the relationship between pairs of training and testing images is not necessarily reciprocal, i.e., good training data are not necessarily good testing data. Simple DOS atmospheric corrections produce classifications with comparable accuracies as classifications from the more complex radiative transfer corrections. These findings are based on over 200 classifications. A high degree of variability in the classification accuracies underscores the importance of extensive, in-depth analysis of remote sensing techniques and applications, and highlights the potential problem for misleading results based on just a few tests. Generalization is well suited for multitemporal classifications of one Landsat scene. Using simple DOS and midsummer images, generalization offers the opportunity for frequent landcover mapping of a Landsat scene without having to retrain the classifier for each time period of interest. However, at this point, the utility of regional landcover mapping with a generalized classifier remains limited.
Event-based detection of concurrency

Understanding the behavior of a system is crucial in being able to modify, maintain, and improve the system. A particularly difficult aspect of some system behaviors is concurrency. While there are many techniques to specify intended concurrent behavior, there are few, if any, techniques to capture and model actual concurrent behavior. This paper presents a technique to discover patterns of concurrent behavior from traces of system events. The technique is based on a probabilistic analysis of the event traces. Using metrics for the number, frequency, and regularity of event occurrences, a determination is made of the likely concurrent behavior being manifested by the system. The technique is useful in a wide variety of software engineering tasks, including architecture discovery, reengineering, user interaction modeling, and software process improvement.
Hempel’s logic of confirmation

This paper presents a new analysis of C.G. Hempel’s conditions of adequacy for any relation of confirmation [Hempel C. G. (1945). Aspects of scientific explanation and other essays in the philosophy of science. New York: The Free Press, pp. 3–51.], differing from the one Carnap gave in §87 of his [1962. Logical foundations of probability (2nd ed.). Chicago: University of Chicago Press.]. Hempel, it is argued, felt the need for two concepts of confirmation: one aiming at true hypotheses and another aiming at informative hypotheses. However, he also realized that these two concepts are conflicting, and he gave up the concept of confirmation aiming at informative hypotheses. I then show that one can have Hempel’s cake and eat it too. There is a logic that takes into account both of these two conflicting aspects. According to this logic, a sentence H is an acceptable hypothesis for evidence E if and only if H is both sufficiently plausible given E and sufficiently informative about E. Finally, the logic sheds new light on Carnap’s analysis.
Adopting Gender-Inclusive Language Reforms: Diachronic and Synchronic Variation

Previous research demonstrates a decline across time in gender-exclusive language among language users who are occupationally mandated to conform to nonsexist language guidelines (e.g., journalists...
Protein extraction and activity in reverse micelles of a nonionic detergent

We describe, for the first time, the ability of a polyoxyethylene sorbitan trioleate-isopropanol microemulsion in hexane to solubilize pure proteins. The dependences of cytochrome c extraction and buffer solubilization by the reverse micellar system on ionic strength of the aqueous phase, detergent concentration, and cosurfactant concentration result in increased extraction. In addition, subtilisin (a serine protease) is shown to be active in this microemulsion. Further the activity of the enzyme can be regulated by the water content of the micelles, enabling control of enzyme activity by "solvent engineering."
The Effects of Infrared-Blocking Pigments and Deck Venting on Stone-Coated Metal Residential Roofs

Field data show that stone-coated metal shakes and S-mission tile, which exploit the use of infraredblocking color pigments (IrBCPs), along with underside venting reduce the heat flow penetrating the conditioned space of a residence by 70% compared with the amount of heat flow penetrating roofs with conventional asphalt shingles. Stone-coated metal roof products are typically placed on battens and counter-battens and nailed through the battens to the roof deck. The design provides venting on the underside of the metal roof that reduces the heat flow penetrating a home. The Metal Construction Association (MCA) and its affiliate members installed stone-coated metal roofs with shake and S-mission tile profiles and a painted metal shake roof on a fully instrumented attic test assembly at Oak Ridge National Laboratory (ORNL). Measurements of roof, deck, attic, and ceiling temperatures; heat flows; solar reflectance; thermal emittance; and ambient weather were recorded for each of the test roofs and also for an adjacent attic cavity covered with a conventional pigmented and direct nailed asphalt shingle roof. All attic assemblies had ridge and soffit venting; the ridge was open to the underside of the stone-coated metal roofs. A control assembly with a conventional asphalt shingle roof was used for comparing deck and ceiling heat transfer rates.
Personality traits in women with multiple sclerosis: discrepancy in patient/partner report and disease course.

Objective Patients diagnosed with multiple sclerosis (MS) are believed to undergo personality changes, which could have implications for how they perceive themselves and are perceived by others. We endeavored to examine the extent to which patients' self-perceptions are congruent with how they are perceived by significant others across five trait domains as demarcated by the well known Five-Factor Model (FFM).
Optimum image thresholding via class uncertainty and region homogeneity

Thresholding is a popular image segmentation method that converts a gray-level image into a binary image. The selection of optimum thresholds has remained a challenge over decades. Besides being a segmentation tool on its own, often it is also a step in many advanced image segmentation techniques in spaces other than the image space. We introduce a thresholding method that accounts for both intensity-based class uncertainty-a histogram-based property-and region homogeneity-an image morphology-based property. A scale-based formulation is used for region homogeneity computation. At any threshold, intensity-based class uncertainty is computed by fitting a Gaussian to the intensity distribution of each of the two regions segmented at that threshold. The theory of the optimum thresholding method is based on the postulate that objects manifest themselves with fuzzy boundaries in any digital image acquired by an imaging device. The main idea here is to select that threshold at which pixels with high class uncertainty accumulate mostly around object boundaries. To achieve this, a threshold energy criterion is formulated using class-uncertainty and region homogeneity such that, at any image location, a high energy is created when both class uncertainty and region homogeneity are high or both are low. Finally, the method selects that threshold which corresponds to the minimum overall energy. The method has been compared to a maximum segmented image information method. Superiority of the proposed method was observed both qualitatively on clinical medical images as well as quantitatively on 250 realistic phantom images generated by adding different degrees of blurring, noise, and background variation to real objects segmented from clinical images.
The KidsRoom: A Perceptually-Based Interactive and Immersive Story Environment

The KidsRoom is a perceptually-based, interactive, narrative playspace for children. Images, music, narration, light, and sound effects are used to transform a normal child's bedroom into a fantasy land where children are guided through a reactive adventure story. The fully automated system was designed with the following goals: (1) to keep the focus of user action and interaction in the physical and not virtual space; (2) to permit multiple, collaborating people to simultaneously engage in an interactive experience combining both real and virtual objects; (3) to use computer-vision algorithms to identify activity in the space without requiring the participants to wear any special clothing or devices; (4) to use narrative to constrain the perceptual recognition, and to use perceptual recognition to allow participants to drive the narrative; and (5) to create a truly immersive and interactive room environment. We believe the KidsRoom is the first multi-person, fully-automated, interactive, narrative environment ever constructed using non-encumbering sensors. This paper describes the KidsRoom, the technology that makes it work, and the issues that were raised during the system's development. 1 A demonstration of the project, which complements the material presented here and includes videos, images, and sounds from each part of the story is available at .
Parenting Styles and Children’s Emotional Intelligence: What do We Know?

The theory of emotional intelligence has elicited great interest both in the academic and the nonacademic world. Therapists, educators, and parents want to know what they can do to help children de...
Arctic air chemistry: Haze analysis

The microparticulate (i.e., aerosol) and gas concentrations in Arctic air masses are being assessed currently as a result of a large-scale, multinational cooperative study made this spring. It turns out that many of the ideas about the origin of Arctic haze, industrial pollution, soil particles from the great desert regions of eastern China and Mongolia, and seasonal effects, to name a few, may all be valid. A recent report about the first extended airborne measurements of Arctic haze that were made during March and April of this year stated: “Most of the scientists on board the NOAA plane found the haze to be much denser and more extensive than they anticipated” (Environ. Sci. Technol., June 1983). The results of WP-30 Orion research aircraft flights over the Arctic ice cap suggest that in some locations the haze extends upward of 8.5 km at this time of the year. The haze was found to exist at all latitudes in the northern polar region with unbroken continuity to an altitude of approximately 3 km. At higher altitudes there was a banding of discontinuous haze layers.
A Randomized, Controlled Trial Comparing Twice-a-Day Insulin Glargine Mixed With Rapid-Acting Insulin Analogs Versus Standard Neutral Protamine Hagedorn (NPH) Therapy in Newly Diagnosed Type 1 Diabetes

OBJECTIVE Insulin glargine is difficult to use for children due to the number of injections required because it is claimed to be immiscible with rapid-acting insulin analogs. For this study, we hypothesized that treating new-onset type 1 diabetes with twice-daily insulin glargine plus a rapid-acting insulin analog mixed in the same syringe would result in better glycosylated hemoglobin than twice-daily neutral protamine Hagedorn with a rapid-acting insulin analog (standard treatment). METHODS Forty-two patients with new-onset type 1 diabetes were started on standard treatment. Three months after diagnosis, if patients were found compliant and had a glycosylated hemoglobin level of < or = 9%, then they were randomly assigned either to receive insulin glargine twice daily mixed with a rapid-acting insulin analog or to continue on standard treatment for 3 more months. Additional lunchtime rapid-acting insulin analog injections were given for the insulin glargine group as necessary. RESULTS Nineteen patients in the insulin glargine group and 17 in the neutral protamine Hagedorn group completed the study. The glycosylated hemoglobin level at baseline was 6.8% +/- 1% vs 6.9% +/- 1% and at poststudy was 6.7% +/- 1.3% vs 7.6% +/- 1% in the insulin glargine versus neutral protamine Hagedorn group, respectively. Two patients in the insulin glargine group required lunch rapid-acting insulin analog in the last month of the study. Although both groups were encouraged to contact the principal investigator with all queries, more in the insulin glargine arm opted to do so. CONCLUSIONS Glycemic control with insulin glargine mixed with a rapid-acting insulin analog given twice daily seems significantly more effective than the standard therapy in newly diagnosed type 1 diabetes. Furthermore, it decreases pain and burden of injections for children with diabetes by allowing patients to mix glargine with rapid-acting insulin analog.
Consumer Welfare Effects of Quantity Changes in Demand

Information about consumer welfare effects associated with quantity changes in demand is important for agricultural and food policy decision-makers because many policy options are directly related to controlling supplies as a means to stabilize or raise commodity prices and farmers' income. A new method is developed to measure the consumer welfare effects by using the estimates of an inverse demand system and a modified quantity-adjusted Malmquist index to represent the efficiency in quantity metric welfare. The methodology is validated by applying it to a U.S. inverse food demand system consisting of 13 food groups and a nonfood sector.
Complementary apodized grating waveguides for tunable photonic delay lines

A novel class of tunable integrated photonic delay lines that compromises between loss and size is proposed. The devices comprise cascaded apodized grating waveguides with complementary (positively and negatively modulated) refractive index profiles.
Synthesis and antineoplastic activity of bis-diazeniumdiolate analogues of the nitric oxide-generating prodrug JS-K

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 5711 Diazeniumdiolate ions, also known as NONOates, are extensively used in biochemical, physiological and pharmacological studies for controlled release of nitric oxide (NO.) and /or its congeneric nitroxyl (HNO) at physiological pH. They can be derivatized at the terminal oxygen to produce charge neutral derivatives that are proving useful as potential drugs, molecules that are stable in aqueous media but capable of generating nitric oxide beneficially when the protecting group is hydrolytically or enzymatically removed in the target cell. Compounds of the O 2-aryl diazeniumdiolate family have shown noteworthy anticancer activity in a variety of model systems; for example, O 2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K has shown antineoplastic activity in vitro and in vivo in leukemia, multiple myeloma, prostate cancer and hepatoma rodent models. In this regard, we have continued to synthesize and diversify libraries of O 2-arylated diazeniumdiolates for additional screening and possible lead optimization. To this end, we prepared a series of bis-diazeniumdiolates and checked their in vitro activities towards different cancer cell lines. Initial screening was performed using the HL-60 human leukemia cell line and two human lung adenocarcinoma cell lines (H1944 and H1703). The IC50 values for bis-diazeniumdiolates analyzed were between 0.8 - 5 μM (72h). The three compounds that showed the highest potency at the initial screening were selected for further studies. They have been tested using a panel of ten cell lines derived from different human cancers (leukemia cell lines, lung adenocarcinoma cell lines, colon, ovarian, and one prostate carcinoma). All three compounds tested showed similar potency in inhibiting proliferation of cancer cells, and appear to be most active towards colorectal carcinoma and leukemia cell lines. The mechanisms of the observed cellular growth inhibition by these bis-diazeniumdiolates require further study. Nitric oxide release from bis-diazeniumdiolates may cause increase in oxidative/nitrosative stress, resulting in DNA damage and apoptosis. The irreversible arylation of glutathione and other cellular nucleophiles required to initiate NO release may also contribute to the toxicity. Furthermore, attachment of glutathione to cysteine residues in proteins (glutathionylation) is a posttranslational modification that can alter protein structure and function. Glutathionylation has been shown for the JS-K analogue PABA/NO (Townsend et al , Mol. Pharmacol. 2006, 69, 501-508). We observed rapid and massive protein glutathionylation occurring within 2 minutes of treatment with 1 µM bis-diazeniumdiolates. Our data suggest that all three mechanisms - glutathionylation, arylation and nitrosative stress - are involved in the cytotoxic activity of bis-diazeniumdiolates against cancer cells.
Equilibrium and Flux Surface Issues in the Design of the NCSX

Equilibrium issues encountered in the design of the National Compact Stellarator Experiment (NCSX) are discussed, focusing particularly on equilibrium magnetic islands. Significant improvements have been made to the VMEC equilibrium code to deal with numerical challenges at the low aspect ratios characterizing the NCSX design. Modifications to the PIES code have increased its speed, allowing routine evaluation of flux surfaces for candidate configurations. An optimizer has been built around the PIES code for healing magnetic islands, modifying the coil shapes to suppress resonant components of the magnetic field while preserving desired physics and engineering properties. The modified coils produce improved flux surface quality for a range of configurations. Neoclassical effects, which are not included in the PIES calculations, are estimated using a cylindrical model and are found to further reduce island widths significantly.
Book Review: Making Thinking Visible

Recent trends in medical education emphasize the importance of producing well-rounded graduates who not only possess a sufficient fund of medical knowledge but who can think clearly and deeply. Unfortunately, many medical educators struggle with what exactly it means to “think” and do not know where to begin when asked to teach “thinking.” We believe the book Making Thinking Visible , though written for K-12, will be of great interest to medical educators. The book describes different types of thinking and presents more than 20 teaching routines that can help engage learners and improve learning to think.
The Riddle of the Fourteenth Amendment: A Response to Professor Wildenthal

Professor Bryan Wildenthal makes an impressive contribution to the debate about whether ratification of the Fourteenth Amendment acted to "incorporate" the Bill of Rights so that its protections are enforceable against the states. His signal achievement is to develop a metric that facilitates making a judgment about whether the states had sufficient notice of the intent of at least some in Congress to incorporate the Bill of Rights into Section 1. He concludes that the states ratified with adequate notice of incorporation. In George Thomas's reply to Wildenthal, he reviews the evidence and concludes that it is insufficient to meet Wildenthal's metric and thus is insufficient to show that the states knew of congressional intent to incorporate. This does not, for Thomas, end the debate because the evidence is also insufficient to show that the states were not aware of the intent to incorporate. For Thomas, the historical question remains a riddle.
A Framework to Identify Best Quality Management Practices and Techniques for Diverse Production Ramp-Up Environments: Propositions for Future Research

Dynamic competitive mechanisms have driven international manufacturers to increase the rate at which new products are introduced to the global market. Introducing new products faster enables firms to sell at higher volumes and prices, resulting in highe..
Research to Controversy in 10 Decades

This article investigates the persistent and change elements of educational testing and assessment from 1920 to the present day. I show by examining the addresses and texts of American Educational Research Association presidents a continuing focus on schools, from early experiments and development up through applications in accountability systems. Continuing topics include sources of test content and uses of tests for equity, effectiveness, support of teaching, and comparisons of alternative methods through experiments or references to standards. Although early writers appeared very close to school practices, later discussions expanded implications for policy uses.
Simulated annealing utilizing neural networks for discrete variable optimization problems in structural design

R. A. Swift t and S. M. Batill tt Hessert Center for Aerospace Research Department of Aerospace and Mechanical Engineering University of Notre Dame Noue Dame, Indiana 46556 A simulated annealing application to the optimal design of structures involving discrete design variables is presented. Neural networks were used as approximate representations of the design spaces for candidate structural concepts. The simulated annealing algorithm was used to search these discrete design spaces. Design information obtained from finite element analysis and math-programming optimization was used to train the neural network representations. Three examples are presented. The first is a material system design of a 10 bar truss in which four isotropic materials were considered for each of the 10 axial force rods. Minimum weight was considered as the objective function. The second example is an ACOSS I1 space truss in which four materials were considered for each of the 113 rod elements, minimum weight being again the objective function. The final example is that of an Intermediate Complexity Wing (ICW), in which a discrete set of lamina orientations was considered for the composite skin, natural frequency being considered as the objective function. In each of the examples, the ability of the neural network to represent the desired information was achieved, and the simulated annealing procedure was able to extract improved designs (improved over the "best" designs in the training data).
The Rich Get Richer and So Can You: Investing in a Billionaires’ Index

Are the rich getting richer? Our data suggest so. Rather than complaining about the unfairness of it all, this article offers a simple approach for the average investor to get richer, too. An index of publicly traded stocks controlled, created, or managed by the world’s wealthiest individuals, known as the Billionaires’ Index, tracks the annual list compiled by Forbes magazine. It doesn’t work every year, but on average, it seems to provide excellent results. Will the new Index work in the future for you?
CHOLECYSTOKININ RAPIDLY ACTIVATES MITOGEN-ACTIVATED PROTEIN KINASE IN RAT PANCREATIC ACINI

The existence and activation of mitogen-activated protein (MAP) kinase in isolated pancreatic acini have been demonstrated. Immunoblotting and immunoprecipitation revealed two forms of MAP kinase in pancreatic acini, with relative molecular masses of approximately 42 and 44 kDa. Both forms of MAP kinase were activated by cholecystokinin (CCK). The threshold concentration of CCK was approximately 3 pM, and the maximal effect occurred at 1 nM, which enhanced MAP kinase activity by 2.5-fold, as determined in polyacrylamide gel copolymerized with substrate myelin basic protein. Activation of MAP kinase by CCK was rapid, reaching a maximum within 5-10 min that subsequently declined. Bombesin and carbachol but not secretin or vasoactive intestinal peptide also activated MAP kinase. CCK-induced activation of MAP kinase may be mediated by protein kinase C, since 12-O-tetradecanoylphorbol 13-acetate (TPA) mimicked the effect of CCK and staurosporine concentration dependently inhibited the action of CCK. Treatment of acini with thapsigargin, ionomycin, or ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid did not influence MAP kinase, indicating that mobilization of intracellular calcium by CCK is not important in activation of acinar MAP kinase. CCK and TPA increased tyrosine phosphorylation of both 42- and 44-kDa forms. Genistein and tyrphostin 23, the inhibitors of tyrosine kinase, suppressed the activation of MAP kinase by CCK. In conclusion, MAP kinase in pancreatic acini is activated by agonists related to hydrolysis of phosphoinositide, via a mechanism involving protein kinase C and tyrosine kinase.
Beta-adrenergic regulation of H+ secretion by cultured outer medullary collecting duct cells.

The effects of the beta-adrenergic agonist isoproterenol (Iso) on cells of the inner stripe portion of the rabbit outer medullary collecting duct (OMCDi) grown in primary culture were examined using whole cell patch-clamp techniques and measurements of intracellular pH (pHi) and Ca2+. Iso (10(-6) M) increased the cellular Cl- conductance, and this effect was mimicked by treatment of the cells with dibutyryladenosine 3',5'-cyclic monophosphate (cAMP, 10(-5) M) or protein kinase A (PKA, 0.4 U/ml). Iso did not alter the baseline pHi, but it did increase the activity of both the Cl-/HCO3- antiporter and the H(+)-adenosinetriphosphatase (H(+)-ATPase). The increase in Cl-/HCO3- antiporter rate was mimicked by dibutyryl-cAMP plus 3-isobutyl-1-methylxanthine (cAMP + IBMX, 10(-4) M + 10(-5) M). However, the Iso-induced stimulation of the H(+)-ATPase activity was not mimicked by cAMP + IBMX. Measurements of intracellular Ca2+ showed that Iso also increased intracellular Ca2+ levels. This response was not dependent ...
Stop Apologizing for Your Samples, Start Embracing Them

Landers and Behrend (2015) call for editors and reviewers to resist using heuristics when evaluating samples in research as well as for researchers to cautiously consider choosing the samples appropriate for their research questions. Whereas we fully agree with the former conclusion, we believe the latter can be extended even further to encourage researchers to embrace the strengths of their samples for understanding their research rather than simply defending their samples. We believe that samples are not inherently better or worse but rather better suited for different research objectives. In this commentary, we identify three continua on which research goals can differ to demonstrate that all samples can inform science. Depending on the position of one's research on these continua, different samples exhibit different strengths; the continua described below can be used to anchor one's sample to demonstrate how it can benefit, rather than limit, research conclusions. As discussed in the focal article, researchers will often apologize for their convenience samples as one of a litany of limitations; we hope that researchers will move sampling issues out of the limitations section and into the main discussion.
Temporary, Systemic Inhibition of the WNT/β-Catenin Pathway promotes Regenerative Cardiac Repair following Myocardial Infarct

Aims The WNT/β-catenin pathway is temporarily activated in the heart following myocardial infarction (MI). Despite data from genetic models indicating both positive and negative roles for the WNT pathway depending on the model used, the effect of therapeutic inhibition of WNT pathway on post-injury outcome and the cellular mediators involved are not completely understood. Using a newly available, small molecule, GNF-6231, which averts WNT pathway activation by blocking secretion of all WNT ligands, we sought to investigate whether therapeutic inhibition of the WNT pathway temporarily after infarct can mitigate post injury cardiac dysfunction and fibrosis and the cellular mechanisms responsible for the effects. Methods and results Pharmacologic inhibition of the WNT pathway by post-MI intravenous injection of GNF-6231 in C57Bl/6 mice significantly reduced the decline in cardiac function (Fractional Shortening at day 30: 38.71 ± 4.13% in GNF-6231 treated vs. 34.89 ± 4.86% in vehicle-treated), prevented adverse cardiac remodeling, and reduced infarct size (9.07 ± 3.98% vs. 17.18 ± 4.97%). WNT inhibition augmented proliferation of interstitial cells, particularly in the distal myocardium, inhibited apoptosis of cardiomyocytes, and reduced myofibroblast proliferation in the peri-infarct region. In vitro studies showed that WNT inhibition increased proliferation of Sca1+ cardiac progenitors, improved survival of cardiomyocytes, and inhibited collagen I synthesis by cardiac myofibroblasts. Conclusion Systemic, temporary pharmacologic inhibition of the WNT pathway using an orally bioavailable drug immediately following MI resulted in improved function, reduced adverse remodeling and reduced infarct size in mice. Therapeutic WNT inhibition affected multiple aspects of infarct repair: it promoted proliferation of cardiac progenitors and other interstitial cells, inhibited myofibroblast proliferation, improved cardiomyocyte survival, and reduced collagen I gene expression by myofibroblasts. Our data point to a promising role for WNT inhibitory therapeutics as a new class of drugs to drive post-MI repair and prevent heart failure.
An Empirical Examination of Management of Real Options in the U.S. Venture Capital Industry

This study empirically examines how firms manage real options over time in the context of the U.S. venture capital industry. It tracks the venture-capital funding histories of U.S. portfolio companies founded during 1989–1993, and their outcomes, until 2004. An examination of sequential investments suggests asymmetries in the management of successful and unsuccessful companies. Signals of a company's progress, such as the number of its patents, are significant predictors of VC investment practices in the case of successful companies, but not in the case of unsuccessful companies. In contrast, VC firm characteristics, such as experience in the company's industry, IPO experience, and geographic proximity, appear to explain variance in investment policies for unsuccessful companies, but not successful ones. This suggests that signals of progress are relatively easier to interpret when real options perform well over time, and investors can perhaps apply them equally effectively. In contrast, signals of failure are more ambiguous and complex; and firm-level differences are more pronounced in the management of unsuccessful options.
Ecosystem Services and Disservices for a Vulnerable Population: Findings from Urban Waterways and Wetlands in an American Desert City

Vulnerable human populations are exposed to social and biophysical stressors, but have limited capacity to mitigate them, and thus may access ecosystem services in unconventional ways. As a result of this access, they may also experience disservices (i.e., functions of ecosystems harmful to human wellbeing) in ways that are not well understood. We use a mixed-method socio-ecological approach to examine how persons experiencing homelessness in Phoenix, Arizona, access ecosystem services and encounter disservices in urban waterways. We find that urban waterways provide users with drinking and bathing water, and cooler, shaded areas, but potentially expose them to pathogens and legal persecution. The wetlands provide cultural services by affording a sense of place and safety; however, these locations can also be associated with restrictive ordinances and aggressive law enforcement. This study explores the role of ecosystem services and disservices in bridging the gap between biophysical and social vulnerability.
The VALUE of Assessment: Transforming the Culture of Learning

When the accreditation email appeared in my inbox as our university's institutional liaison, a chill went down my spine—it was time to start gearing up for the self-study of our institution that wo...
Seeing Salvation: Authority and Apocalypse in Saint Paul and the Nizari Ismaili Qiyāma

This article develops Marshall Hodgson’s initial observations concerning the affinities between the theologies of Paul of Tarsus and the Nizari Ismaili declaration of the qiyāma, or resurrection, o...