cssi/SciSciGPT-SciSciNet huggingface dataset:
A Chimeric Analysis of the Opioid Receptor Domains Critical for the Binding Selectivity of μ Opioid Ligands

The mu opioid receptor plays a key role in mediating the physiological, pharmacological, and behavioral effects of endogenous opioids and of opiate drugs such as morphine and heroin. This study examines the structural features critical to the selective binding of mu ligands to the mu receptor as opposed to the other two highly homologous opioid receptors, delta and kappa. We use a series of chimeric constructs between the mu and either the delta or the kappa receptors to investigate the structural bases of binding selectivity of multiple classes of mu-selective ligands. Our results demonstrate that a region comprising the sixth transmembrane domain and the third extracellular loop is critical for the mu/kappa discrimination by all mu-selective ligands. This region is also critical for mu/delta discrimination by the mu antagonists. However, mu agonists, particularly the peptides, exhibit more complex interactions, often relying on the N-terminal region surrounding the first extracellular loop for mu/delta discrimination. Thus, the same mu peptide ligand depends on different parts of the receptor to discriminate between mu and delta receptors on the one hand and mu and kappa on the other. In general, antagonists show the most consistent discrimination mechanisms regardless of construct, whereas agonists, particularly peptides, achieve selectivity by interacting with numerous domains of the receptors.
Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor

Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse.
Immunology and the REACH Study: HIV immunology and preliminary findings

This review paper presents the immunology findings in human immunodeficiency virus (HIV) infected and uninfected youth in the Reaching for Excellence in Adolescent Care and Health (REACH) Project within the context of basic and HIV immunology concepts. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This paper reviews published analyses of cross-sectional data; longitudinal analyses are underway. These preliminary data extend the work of others in demonstrating the potential for substantial thymic reserve in youth. This finding in HIV infected adolescents has implications for a fuller response to antiretroviral or immune-based therapies compared to that seen in adults. Dysregulation in mucosal immunity may appear before systemic HIV effects are seen and requires attention particularly to screening and treatment of genital co-infections. REACH has demonstrated gender differences in immunologic measures irrespective of HIV infection status.
Excretion and measurement of estradiol and progesterone metabolites in the feces and urine of female squirrel monkeys (Saimiri sciureus).

The first objective of the present study was to determine the metabolic form and rate of excretion of ovarian hormone metabolites in the urine and feces of female squirrel monkeys injected with radiolabeled progesterone (Po) and estradiol. The major portion of the urinary metabolites of both hormones was excreted within 16-24 hr post-injection. Estrogen and Po isotopes in feces exhibited an excretion peak at 16 hr post-injection. The majority of recovered radiolabel of both hormones was excreted in feces. Chromatographic separation of fecal extractions indicated that the major estrogen metabolites in feces are in the free as opposed to the conjugated form. The radioactivity and immunoreactivity for estrone and estradiol (E(1) and E(2), respectively) in eluates of fecal samples subjected to celite co-chromatography indicated that both free E(1) and E(2) exist as excretion products in the feces of female squirrel monkeys. The major radioactive peaks for Po metabolites showed peaks in the elution profile at or very near the Po standard, and corresponded with the celite co-chromatography elution profile of Po standard when subjected to enzyme immunoassay (EIA). The second objective was to validate the application of EIA systems to measure fecal metabolites. Reproductive events of one female squirrel monkey across one annual reproductive cycle are described using the endocrine profile generated from fecal steroid assays. Examination of this profile confirmed that longitudinal fecal sampling and steroid hormone metabolite measurement in feces was not only feasible and practical, but accurately detected known reproductive events as well.
Turning around failing organizations: Insights for educational leaders

Purpose In this article, we review the literature from the organizational sciences to develop a grounded narrative of turnaround in education. Approach The approach is a review of literature. We employ an integrated process to unpack and make sense of the turnaround literature from the organizational sciences. We rely on strategies appropriate for document analysis, and borrow analytic strategies (e.g., memoing, coding) employed with interview data. Findings We examine seven defining themes that flow from our review of empirical and theoretical work on organizational recovery in firms, non-educational public agencies, and not-for-profit organizations: (1) not all failing schools are worth saving; (2) focus on leadership; (3) act quickly; (4) diagnose first; (5) emphasize efficiency moves; (6) create a sense of hope; and (7) backward map from the customer and focus on core activities linked to valued outcomes. Implications We posit that the literature on turning around failing organizations in sectors outside of education provides blueprints for recovery activity in failing schools. The implications for turnaround leadership are particularly strong. Originality This is the first systematic effort to mine research in the corporate, not-for-profit, and public sectors to develop insights for turning around failing schools.
Modeling of femtosecond pulse interaction with inhomogeneously broadened media using an iterative predictor corrector FDTD method

We present a one-dimensional iterative predictor-corrector finite-difference time-domain method for modeling of broadband optical pulse propagation and interaction with inhomogeneously broadened materials. The simulator is used to demonstrate two- and three-pulse photon echoes resulting from bandwidth limited pulse and matched chirp interactions with a material modeled with hundreds of equally spaced, discrete spectral lines of detuning. The results are illustrated as Bloch-sphere evolution movies.
Comparison of computational collisional models in a drift tube

Computational modeling is one of the principal tools for studying collisional plasma discharges, such as capacitive, inductive, and DC discharges. The optimal model depends upon the regime of operation, often characterized by the ratio E/N, where E is the electric field, and N is the number density. A number of electron-neutral collisional models are compared for a range of E/N values of interest in discharge modeling, including a particle-in-cell Monte-Carlo collision (PIC-MCC) code, a Direct Simulation Monte Carlo (DSMC) code, and two Boltzmann codes employing different algorithms. The comparison explores differences in the reaction rates, which can strongly influence the behavior of the discharge. Due to the nonlinear nature of discharges, the study focuses on a drift tube with constant field and uniform background gas. Swarm data is gathered to obtain electron energy distribution functions, as well as moments including drift velocity and mean energy. In addition, rates are compared for elastic scattering, excitation and ionization processes in neon. Ion and space charge effects are neglected in this study.
Evaluating the potential of multispectral imagery to map multiple stages of tree mortality

Abstract Insect outbreaks are major forest disturbances, causing tree mortality across millions of ha in North America. Resultant spatial and temporal patterns of tree mortality can profoundly affect ecosystem structure and function. In this study, we evaluated the classification accuracy of multispectral imagery at different spatial resolutions. We used four-band digital aerial imagery (30-cm spatial resolution and aggregated to coarser resolutions) acquired over lodgepole pine-dominated stands in central Colorado recently attacked by mountain pine beetle. Classes of interest included green trees and multiple stages of post-insect attack tree mortality, including dead trees with red needles (“red-attack”), dead trees without needles (“gray-attack”), and non-forest. The 30-cm resolution image facilitated delineation of trees located in the field, which were used in image classification. We employed a maximum likelihood classifier using the green band, Red–Green Index (RGI), and Normalized Difference Vegetation Index (NDVI). Pixel-level classification accuracies using this imagery were good (overall accuracy of 87%, kappa = 0.84), although misclassification occurred between a) sunlit crowns of live (green) trees and herbaceous vegetation, and b) sunlit crowns of gray- and red-attack trees and bare soil. We explored the capability of coarser resolution imagery, aggregated from the 30-cm resolution to 1.2, 2.4, and 4.2 m, to improve classification accuracy. We found the highest accuracy at the 2.4-m resolution, where reduction in omission and commission errors and increases in overall accuracy (90%) and kappa (0.88) were achieved, and visual inspection indicated improved mapping. Pixels at this resolution included more shadow in forested regions than pixels in finer resolution imagery, thereby reducing forest canopy reflectance and allowing improved separation between forest and non-forest classes, yet were fine enough to resolve individual tree crowns better than the 4.2-m imagery. Our results illustrate that a classification of an image with a spatial resolution similar to the area of a tree crown outperforms that of finer and coarser resolution imagery for mapping tree mortality and non-forest classes. We also demonstrate that multispectral imagery can be used to separate multiple postoutbreak attack stages (i.e., red-attack and gray-attack) from other classes in the image.
Global change and the intensification of agriculture in the tropics

zAbstract Bridging understanding of local environmental change with regional and global patterns of land-use and land-cover change (LUCC) remains a key goal and challenge for our understanding of global environmental change. This meta-analysis attempts to bridge local and regional scales of LUCC by demonstrating the ways in which previously published case studies can be compared and used for a broader regional synthesis in the tropics. In addition to providing results from a meta-analysis, this paper suggests ways to make future case studies more widely comparable.
Weed Control in Soybean under Different Cropping and Tillage Systems

Studies were established in 1987 and 1988 near Brooksville and Poplarville, MS, to evaluate six weed-control systems in monocrop soybean [Glycine max (L.) Merr.] and doublecrop wheat (Triticum aestivum L.) ― soybean planted both with and without prior tillage. (...)
Aging impairs IFN regulatory factor 7 up-regulation in plasmacytoid dendritic cells during TLR9 activation.

Plasmacytoid dendritic cells (pDCs) are innate sensors that produce IFN- in response to viral infections. Determining how aging alters the cellular and molecular function of these cells may provide an explanation of increased susceptibility of older people to viral infections. Hence, we examined whether aging critically impairs pDC function during infection with HSV-2, a viral pathogen that activates TLR9. We found that impaired IFN- production by aged murine pDCs led to impaired viral clearance with aging. Upon TLR9 activation, aged pDCs displayed defective up-regulation of IFN-regulatory factor 7, a key adaptor in the type I IFN pathway, as compared with younger counterparts. Aged pDCs had more oxidative stress, and reducing oxidative stress in aged pDCs partly recovered the age-induced IFN- defect during TLR9 activation. In sum, aging impairs the type I IFN pathway in pDCs, and this alteration may contribute to the increased susceptibility of older people to certain viral infections. The Journal of Immunology, 2008, 181: 6747–6756.
Content/Construct Approaches in Life History Form Development for Selection

Life history, or biodata, inventories are attractive alternatives to cognitive ability tests for selection, but they have been frequently criticized for their low construct validity and the a-theoretical nature of their items. Little guidance in the literature is provided for developing good construct-valid biodata measures. Using a content/construct-oriented approach, a biodata form was developed and validated. The methods for developing and validating the form are thoroughly described so as to provide guidelines for future researchers, and evidence for the meaningfulness of the scales is presented.
Some relationships of structure to function in ribonuclease.

This study by White and Anfinsen on the renaturation of fully denatured ribonuclease, or RNase, required subsequent supporting investigations to establish what came to be called the "thermodynamic hypothesis." Here they reported that RNase activity depended upon a variety of structural features, but noted that it could be inferred from the results of their experimentation that only a small part of the enzyme molecule, what they termed the "active center," was necessary for catalyst.
Optimal Digital Control with Computation Time-Delay: a W-Synthesis Method

In this paper, we treat the control problem for sampled-data systems that accounts for time-delay in the computation of the control action. The problem is formualted entirely in the ?-domain, and the optimum design is solved using an alternative method called Optimal W-Synthesis. The method has been applied to the benchmark problem of a two-mass-spring system. Design results obtained indicate that the presence of computation time-delay not only reduce the relative stability and robustness but also degrades the design performance. Loss in gain and phase margins is significant if the time-delay is not accounted for in the control-law synthesis. However, stability, robustness and performance can be recovered when computation time delay is included in the control-law synthesis.
Application of Ozone with Physical Wastewater Treatments to Recondition Poultry Process Waters

Several wastewater treatments, including direct ozonation and a combination of ozonation with either slow sand filtration, dissolved air flotation, or diatomaceous earth (DE) filtration, were tested for their ability to recondition broiler process waters. The quality of broiler prechiller overflow water was significantly improved with all wastewater treatments examined, surpassing the USDA's recycling requirements in nearly all trials. A combination of screening, DE filtration, and ozonation yielded the highest quality water. With this treatment, significant reductions in chemical oxygen demand, total solids, and the total microbial load including conform bacteria and salmonellae of 87, 65, and 99.9%, respectively, were detected in the reconditioned prechiller water. Percentage of light transmission at 500 nm (%T) of treated water increased to 97 % of tap water and compared favorably with %T of potable water. This same water treatment was tested on final carcass rinse and neck chiller overflow waters. The quality of these treated waters was also significantly improved. It was concluded that poultry process waters could be effectively reconditioned for recycling by screening, DE filtration, and ozonation. Furthermore, wastewater organic loads discharged to wastewater treatment facilities can be effectively reduced through these reconditioning practices. (Key words: ozone, wastewater, recondition, recycling, poultry process water)
Low-latency temporal filter design for real-time MRI using UNFOLD.

To improve real-time control of interventional procedures such as guidance of catheters, monitoring of ablation therapy, or control of dosage during drug delivery, the image acquisition and reconstruction must be high speed and have low latency (small time delay) in processing. A number of different methods have been demonstrated which increase the speed of MR acquisition by decreasing the number of sequential phase-encodes. A design and implementation of the UNFOLD method which achieves the desired low latency with a recursive temporal filter is presented. The recursive filter design is characterized for this application and compared with more commonly used moving average filters. Experimental results demonstrate low-latency UNFOLD for two applications: 1) high-speed, real-time imaging of the heart to be used in conjunction with cardiac interventional procedures; and 2) the injection of drugs into muscle tissue with contrast enhancement, i.e., monitoring needle insertion and injection of a drug with contrast enhancement properties. Proof-of-concept was demonstrated by injecting a contrast agent. In both applications the UNFOLD technique was used to double the frame rate.
Mechanisms of calcium transient and action potential alternans in cardiac cells and tissues.

Alternation of cardiac action potential duration (APD) from beat to beat and concurrent alternation of the amplitude of the calcium transient are regarded as important arrhythmia mechanisms. These ...
Visual scene memory and the guidance of saccadic eye movements

An unresolved question is how much information can be remembered from visual scenes when they are inspected by saccadic eye movements. Subjects used saccadic eye movements to scan a computer-generated scene, and afterwards, recalled as many objects as they could. Scene memory was quite good: it improved with display duration, it persisted over time long after the display was removed, and it continued to accumulate with additional viewings of the same display (Melcher, D. (2001) The persistance of memory for scenes. Nature 412, 401). The occurrence of saccadic eye movements was important to ensure good recall performance, even though subjects often recalled non-fixated objects. Inter-saccadic intervals increased with display duration, showing an influence of duration on global scanning strategy. The choice of saccadic target was predicted by a Random Selection with Distance Weighting (RSDW) model, in which the target for each saccade is selected at random from all available objects, weighted according to distance from fixation, regardless of which objects had previously been fixated. The results show that the visual memory that was reflected in the recall reports was not utilized for the immediate decision about where to look in the scene. Visual memory can be excellent, but it is not always reflected in oculomotor measures, perhaps because the cost of rapid on-line memory retrieval is too great.
Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain

The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the "flight-or-fight" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body ("allostatic load"). Yet, hormones associated with stress protect the body in the short-run and promote adaptation ("allostasis"). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.
Historicizing state sovereignty : Inequality and the form of equivalence

The overarching argument of this paper is not a new one; others have made it in various forms. The argument suggests, in Bernard Cohn's simple formulation, that metropole and colony should be treated in a unified field of analysis. Reconstituting the analytical frame in the manner Cohn suggests has a range of implications not only for the study of colonialism but also, and perhaps more importantly, for understanding current geopolitical conjunctures. The suggestion diverges from the conventional analytical approach that divides and demarcates the world into separable entities—whether they be described as the mutually exclusive categories of metropole and colony, Europe and its Others, a set of distinct nations, first and third world, or indeed of areas and regions—and studies these distinct entities in isolation from, or in comparison with, each other. In contrast, Cohn's proposition asks for an analysis of how such demarcations are produced and of how, rather than being discrete entities with autochthonous formations, they are co-produced through a complex array of related and relational historical events. It is a call, in other words, to shift the analytical framework from one that functions, implicitly or explicitly, on the basis of comparison, to one that operates on the basis of co-production. Such an approach, this essay demonstrates, is especially necessary for a thoroughly historicized understanding of nation-state formation, particularly since the nation-state constitutes a preeminent category of and for comparative analysis.
Comparing different meteorological ensemble approaches: hydrological predictions for a flood episode in Northern Italy

Abstract. Within the framework of coupled meteorological-hydrological predictions, this study aims at comparing two high-resolution meteorological ensembles, covering short and medium range. The two modelling systems have similar characteristics, as almost the same number of members, the model resolution (about 7 km), the driving ECMWF global ensemble prediction system, but are obtained through different methodologies: the former is a multi-model ensemble, based on three mesoscale models (BOLAM, COSMO, and WRF), while the latter follows a single-model approach, based on COSMO-LEPS (Limited-area Ensemble Prediction System), the operational ensemble forecasting system developed within the COSMO consortium. Precipitation forecasts are evaluated in terms of hydrological response, after coupling the meteorological models with a distributed rainfall-runoff model (TOPKAPI) to simulate the discharge of the Reno river (Northern Italy), for a severe weather episode. Although a single case study does not allow for robust and definite conclusions, the comparison among different predictions points out a remarkably better performance of mesoscale model ensemble forecasts compared to global ones. Moreover, the multi-model ensemble outperforms the single model approach.
Recycling of Raft-associated Prohormone Sorting Receptor Carboxypeptidase E Requires Interaction with ARF6

Little is known about the molecular mechanism of recycling of intracellular receptors and lipid raft-associated proteins. Here, we have investigated the recycling pathway and internalization mechan...
Influence of embryonic secretory chemicals on selective oviductal transport in mares

Summary Equine embryos are selectively transported from oviducts to uteri from 5 days 10 h to 5 days 22 h after ovulation. Selective transport appears to be initiated by a characteristic of equine oviductal embryos that is not present in unfertilised ova. To test the hypothesis that selective oviductal transport is initiated by stage-specific secretion of embryonic chemicals, experiments were completed to identify chemicals whose secretion by embryos was temporally associated with oviductal transport, and which initiated oviductal changes that were consistent with oviductal transport. Day-6 embryos incubated in vitro secreted minimal amounts of proteins, steroids and prostaglandin F2α, and relatively high amounts of prostaglandin E2 (PGE2). Embryonic PGE2 secretion was not detected on Day 3 or Day 4, was first detected on Day 5 and in larger amounts on Day 6. PGE2 bound specifically to equine oviducts on Days 2 and 5. Uterine entry of oviductal embryos was hastened in 6 of 11 mares by intraoviductal PGE2 treatment, but was not hastened by saline vehicle treatment or no treatment. These results support the hypothesis that embryonic PGE2 initiates oviductal transport in mares.
Boron based fluoride anion receptors: Electrochemical and sensory applications

Abstract Boron based fluoride anion receptors as electrolyte additives would significantly improve lithium ion battery performance. Fluorinated versions of triarylboranes, boronate esters, boroxines, and other boron based anion receptors have potential applications in the design of high specific energy lithium ion batteries. There is also an emerging interest in recent years in the design of colorimetric sensors for the fluoride anion, especially in aqueous systems, using boron based anion receptors. This mini review highlights the recent trends in the design and applications of the boron based fluoride anion receptors as electrolyte additives and as colorimetric sensors.
Western Corn Rootworm (Coleoptera: Chrysomelidae) Beetle Emergence from Weedy Cry3Bb1 Rootworm-Resistant Transgenic Corn

Abstract Three greenhouse experiments were conducted to evaluate western corn rootworm, Diabrotica virgifera virgifera LeConte, beetle emergence from individual pots containing glyphosate-tolerant transgenic corn, Zea mays L., expressing the Cry3Bb1 endotoxin from the soil bacterium Bacillus thuringiensis Berliner (MON863), nontransgenic glyphosate-tolerant isoline corn, grassy weeds (giant foxtail, Setaria faberi R.A.W. Herrm; and large crabgrass, Digitaria sanguinalis (L.) Scop.), and combinations thereof infested with 40 neonate larvae. In the first two experiments, pots with corn and weed combinations were treated with glyphosate 5 d after larval infestation to kill the weeds. The third experiment was similar to the first two except that untreated corn–weed combinations were added. In all three experiments beetle emergence varied significantly. Beetle recovery generally did not vary between the nontransgenic, nontransgenic + weeds, and MON863 + weeds. Significantly more beetles were recovered from MON...
Darwin's beautiful notion: sexual selection and the plurality of moral codes.

One of the explicit objectives of Darwin's Descent of Man, and Selection in Relation to Sex was to explain cultural differences seen in human beings. Such an explanation, Darwin believed, was to rest upon an understanding of sexual selection. I examine the role that the beautiful plays within the mechanism of sexual selection as it works to differentiate isolated groups. It is suggested that an examination of the relationship between sexual selection and artificial selection - a relationship mediated by the beautiful - will illuminate key issues of the Descent as well as contemporary debates regarding the relationship between evolution and ethics. The beautiful, originally rooted in sexual selection, can become de-coupled from sexual selection and utilized in some selective process which is conscious.
Histone Deacetylase 3 (HDAC3)-dependent Reversible Lysine Acetylation of Cardiac Myosin Heavy Chain Isoforms Modulates Their Enzymatic and Motor Activity

Reversible lysine acetylation is a widespread post-translational modification controlling the activity of proteins in different subcellular compartments. We previously demonstrated that a class II histone deacetylase (HDAC), HDAC4, and a histone acetyltransferase, p300/CREB-binding protein-associated factor, associate with cardiac sarcomeres and that a class I and II HDAC inhibitor, trichostatin A, enhances contractile activity of myofilaments. In this study we show that a class I HDAC, HDAC3, is also present at cardiac sarcomeres. By immunohistochemical and electron microscopic analyses, we found that HDAC3 was localized to A-band of sarcomeres and capable of deacetylating myosin heavy chain (MHC) isoforms. The motor domains of both cardiac α- and β-MHC isoforms were found to be reversibly acetylated. Biomechanical studies revealed that lysine acetylation significantly decreased the Km for the actin-activated ATPase activity of MHC isoforms. By in vitro motility assay, we found that lysine acetylation increased the actin-sliding velocity of α-myosin by 20% and β-myosin by 36% compared with their respective non-acetylated isoforms. Moreover, myosin acetylation was found to be sensitive to cardiac stress. During induction of hypertrophy, myosin isoform acetylation increased progressively with duration of stress stimuli independently of isoform shift, suggesting that lysine acetylation of myosin could be an early response of myofilaments to increase contractile performance of the heart. These studies provide the first evidence for localization of HDAC3 at myofilaments and uncover a novel mechanism modulating the motor activity of cardiac MHC isoforms.
Fifteen-minute consultation: autoimmune encephalitis

Autoimmune encephalitis (AE) is increasingly diagnosed in children, and can result in severe long-term disability. We use a clinical case to illustrate the core clinical features, initial investigations and management of this potentially treatable condition, and describe the common presenting neurological syndromes alongside highlighting differences between each autoantibody subtype.
Yttrium-90 Radioembolization for Hepatocellular Carcinoma

90 Y radioembolization refers to the selective, transcatheter, and intra-arterial injection of micrometer-sized particles loaded with the radioisotope yttrium-90 for the treatment of primary and metastatic hepatic malignancies. In the treatment of intermediate- and advanced-stage hepatocellular carcinoma, 90 Y radioembolization provides favorable outcomes with minimal side effects, offering an alternative treatment option to other transarterial therapies, such as bland embolization and chemoembolization. This review provides an overview of the use of 90 Y radioembolization in the treatment of hepatocellular carcinoma, including patient selection criteria, dosimetry, and clinical outcomes.
Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism

Abstract Objective: Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. Methods: A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 μg/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI-I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks. Results: A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure – the clinician...
Renewal After the Punishment of Free Operant Behavior

Three experiments examined the role of context in punishment learning. In Experiment 1, rats were trained to lever press for food in Context A and then punished for responding in Context B (by presenting response-contingent footshock). Punishment led to complete suppression of the response. However, when responding was tested (in extinction) in Contexts A and B, a strong renewal of responding occurred in Context A. In Experiment 2, renewal also occurred when initial reinforcement occurred in Context A, punishment occurred in Context B, and testing occurred in a new context (Context C). In both experiments, behavioral suppression and renewal were not observed in groups that received noncontingent (yoked) footshocks in Context B. In Experiment 3, 2 responses (lever press and chain pull) were separately reinforced in Contexts A and B and then punished in the opposite context. Although the procedure equated the contexts on their association with reinforcement and punishment, renewal of each response was observed when it was tested in its nonpunished context. The contexts also influenced response choice. Overall, the results suggest that punishment is specific to the context in which it is learned, and establish that its context-specificity does not depend on a simple association between the context and shock. Like extinction, punishment may involve learning to inhibit a specific response in a specific context. Implications for theories of punishment and for understanding the cessation of problematic operant behavior (e.g., drug abuse) are discussed.
Development of Tumor-Targeted Near Infrared Probes for Fluorescence Guided Surgery

Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.
Images in clinical medicine. Use of multinucleated giant cells to diagnose a viral eruption.

University of Kansas Medical Center Kansas City, KS 66160 art of the differential diagnosis of a vesicular eruption must include smallpox. The characteristic smallpox lesions — papulovesicular pustules — develop two to four days after an influenza-like prodrome. The lesions progress from macules to papules to vesicular pustules. The eruption appears first on the face; spreads centrifugally to the scalp, upper chest, back, arms, and hands; and appears last on the abdomen, legs, and feet. The lesions are all in the same stage of development on a given area of the body. The differential diagnosis of the vesicular-pustule stage includes varicella (chickenpox), eczema herpeticum (disseminated herpes), and herpes zoster. One way of differentiating varicella, herpes simplex, and herpes zoster from smallpox is to identify multinucleated giant cells in a Tzanck smear from a fresh vesicle. Smallpox does not produce multinucleated giant cells. The features of the multinucleated giant cell include multinucleation, with molding of the nuclei as they are crowded together (Panel A; Giemsa, ¬400); peripheral margination of the chromatin; and a ground-glass appearance of the nuclei (Panel B; Giemsa, ¬400). The cell may also have a bizarre or atypical shape. The Tzanck preparation shown in Panel A is from a lesion in a 19-year-old woman with atopic dermatitis in whom eczema herpeticum developed from herpes simplex. The preparation in Panel B is from a 32-year-old man with varicella.
NTCT-04SPINAL CORD TOXICITY FROM INTRATHECAL CHEMOTHERAPY: A CASE WITH CLINICOPATHOLOGIC CORRELATION

We report antemortem pathologic and neuroimaging findings of severe myelotoxicity from intrathecal chemotherapy in a case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) complicated by leptomeningeal disease. A 73 year old male was diagnosed with BPDCN after fine needle aspiration of an enlarged cervical lymph node. Total body PET imaging revealed extensive systemic hypermetabolic lymphadenopathy and a staging lumbar puncture was positive for malignant cells. He was treated with etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone (EPOCH) and five doses of intrathecal cytosine arabinoside with the last dose administered on 2 months after diagnosis with CSF clearing. One year later, he developed progressive lower extremity weakness, numbness and bowel/bladder dysfunction. Lumbar spine imaging 4 weeks later revealed subtle linear enhancement along the cauda equina and within the dependent thecal sac, but cervical and thoracic spine MRI at this time were unremarkable. CSF showed atypical lymphoid cells and an Ommaya reservoir was placed. Intrathecal chemotherapy with methotrexate and cytarabine was started. Subsequent CSF analysis showed no malignant cells. However, the patient continued to have progressive ascending weakness and numbness, and his neurologic condition progressed to tetraplegia, low of bowel and bladder control and severe sensory loss, especially to vibration and joint position modalities. Spine MRI showed high signal intensity involving the posterior columns diffusely in the cervico-thoracic spinal cord. Metabolic and infectious work up was negative. A subsequent biopsy of the posterior columns of the lower thoracic spinal cord demonstrated cord destruction with profuse macrophage infiltration without evidence of malignant cells or microorganisms. Treatment with folate and cyanocobalamin resulted in no improvement, and the patient elected for palliative care only. This case illustrates central nervous system involvement by a rare myeloid tumor and demonstrates neuroimaging and unique antemortem pathology of intrathecal chemotherapy-induced myelotoxicity.
3.1 – Alkene Synthesis

In this chapter, the various methods of converting a carbonyl derivative to an alkene are discussed. Particular focus has been given to recently developed methods and their use in the context of natural product synthesis. Formally this volume in the series is devoted to nonstabilized carbanion additions, but this mechanistic definition has not been strictly adhered to in this chapter. The methods are categorized according to the type of alkene synthesized, and the stabilizing group attached to the anion or carbene. In addition, all of the methods discussed involve the addition of a carbon unit to the carbonyl, followed by some type of elimination or cleavage to the alkene. To further narrow the scope of this chapter, the added carbon unit and the original carbonyl carbon must form the units of the alkene, as shown in Scheme 1. Aldehydes, ketones, esters and lactones, and amides and lactams are all featured in these sections, depending on the synthetic method being discussed.
A Reformulation of Tropical Cyclone Potential Intensity Theory Incorporating Energy Production along a Radial Trajectory

AbstractA modified formula for calculating tropical cyclone (TC) potential intensity (PI) from a balance between energy production and frictional dissipation in the TC surface layer is developed. This modified formula accounts for energy production and frictional dissipation at multiple radii (and therefore at multiple wind speeds) along the TC inflow trajectory. The PI maximum wind speed values VMAX are calculated using this expanded formula for four canonical radial profiles of wind speed. These results are compared to PI VMAX values calculated using the standard assumption that all energy production and frictional dissipation relevant to maximum intensity occurs at the radius of maximum winds (RMW).The new PI formulation developed here results in PI VMAX values substantially higher than the standard PI VMAX for all four of the radial wind speed profiles examined; the difference is explained by the increase in the outer radial limit of energy production. This increase holds true even if outflow temperat...
Recovery of select rare and fastidious microorganisms from blood cultures.

The majority of microorganisms that cause sepsis are common pathogenic bacteria and yeasts. Consequently, most commercial blood culture media and laboratory methods are designed to optimize recovery of common microbial pathogens. Occasionally, however, clinical microbiologists are confronted with the need to recover rare or fastidious microorganisms from the blood of septic patients. Although use of commercial media and standard blood culture processing methods are adequate for recovering most of these microorganisms, recovery of certain pathogens requires use of different media or modification of routine laboratory procedures.
Ion–ripple lasers promise cheap, efficient radiation

The University of California, Los Angeles, has been in the business of using plasmas to reduce the scale length of particle accelerators from tens of kilometres to tens of centimetres for over ten years. Now, K R Chen and John Dawson of UCLA have proposed a novel method for producing coherent light from a relativistic electron beam injected into a small region of plasma, which could reduce the scale of free-electron lasers (FELs) from metres to centimetres (Phys. Rev. Lett. (1992) 68 29). This new scheme, the "ion-ripple laser", may some-day provide scientists with a smaller, cheaper and more efficient coherent radiation source than conventional FELs. Similar to the FEL, the ion-ripple laser would operate from microwave to ultraviolet frequencies.
A Skeptical View of the National Science Foundation's Role in Economic Research

We can imagine a plausible case for government support of science based on traditional economic reasons of externalities and public goods. Yet when it comes to government support of grants from the National Science Foundation (NSF) for economic research, our sense is that many economists avoid critical questions, skimp on analysis, and move straight to advocacy. In this essay, we take a more skeptical attitude toward the efforts of the National Science Foundation to subsidize economic research. We offer two main sets of arguments. First, a key question is not whether NSF funding is justified relative to laissez-faire, but rather, what is the marginal value of NSF funding given already existing government and nongovernment support for economic research? Second, we consider whether NSF funding might more productively be shifted in various directions that remain within the legal and traditional purview of the NSF. Such alternative focuses might include data availability, prizes rather than grants, broader dissemination of economic insights, and more. Given these critiques, we suggest some possible ways in which the pattern of NSF funding, and the arguments for such funding, might be improved. Although our discussion here will be phrased in terms of grants for economic research from the National Science Foundation, similar arguments would apply to grants in support of economic research from the National Institutes of Health (which
Neurophysiology of Neuromuscular Transmission and Its Disorders

Despite several antibody tests being available for the assessment of disorders of neuromuscular transmission, electrophysiological testing of the neuromuscular junction remains a very important part of clinical practice. The neuromuscular junction is a complex structure and an understanding of its anatomy and physiology can assist in better understanding the value of electrodiagnostic testing. The most common disorders include myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism, and are usually readily identified using several electrophysiological techniques including slow (2-3 Hz) and fast (20- to 50-Hz stimulation). Single-fiber needle EMG remains an additional powerful and sensitive test for patients with disorders that are more mild, in whom repetitive stimulation testing is negative or indeterminate.
Steady State Over-Modulation of Matrix Converter Using Simplified Carrier Based Control

In this paper, the simplified carrier-based control of matrix converter is modified to operate the converter in the over- modulation region. Both the input-side and output-side over- modulation modes have been studied and their limits of operation are derived. With output-side over-modulation, the maximum output to input voltage transfer-ratio with 6-step square wave output voltage is found to be 0.95 which is higher than the 0.866 intrinsic limit of the matrix converter. With input-side over- modulation the maximum voltage transfer-ratio is found to be 0.908 while still being able to control the power factor of the input currents. With simultaneous input and output-side over- modulation, a unity voltage transfer-ratio is achieved. This improvement in the voltage transfer-ratio in the above three cases is achieved at the cost of low frequency distortion in the output voltages and input currents. With simultaneous input and output- side over-modulation, a voltage transfer-ratio of 0.958 is achieved without significantly increasing the harmonics in the input currents and output voltages. Theoretical calculations are supported by experimental results on a laboratory prototype.