cssi/SciSciGPT-SciSciNet huggingface dataset:
Statistical analysis of drug interactions in anesthesia

Anesthesiologists often use more than one drug in a patient to achieve a target response, such as a desired blood pressure. Isobolographic analysis is a standard mathematical method to test whether a drug-drug interaction exists and, if so, whether the interaction is synergistic or antagonistic. Several experimental protocols are suitable to collect data for interpretation by isobolographic analysis. Traditionally, each subject would receive a single dose of one or more drugs and the presence or absence of the target response in the subject at a specific time would be recorded. An alternative procedure is to infuse one or more drugs into each subject until the target response occurs. This procedure is clinically relevant to studies of anesthesia drugs, which are often titrated to achieve a target response. This latter method of testing for drug interaction requires fewer subjects than the traditional approach because more information is obtained from each subject. We present a statistical test for drug-drug interaction that uses the total doses of drugs given to each subject. This statistical test can be used as part of a complete analysis of drug-drug interaction. We consider (i) selection of appropriate sample sizes and doses; (ii) randomizing subjects to groups; (iii) effects of unequal group variances on the accuracy of the statistical test; (iv) appropriate methods to present the drug-drug interaction data graphically; and (v) tests to ensure that statistical assumptions are satisfied. Using the statistical methods described here, drug-drug interaction can be quantified and evaluated for statistical significance.
Fundamental theories of waves and particles formulated without classical mass

Abstract Quantum and classical mechanics are two conceptually and mathematically different theories of physics, and yet they do use the same concept of classical mass that was originally introduced by Newton in his formulation of the laws of dynamics. In this paper, physical consequences of using the classical mass by both theories are explored, and a novel approach that allows formulating fundamental (Galilean invariant) theories of waves and particles without formally introducing the classical mass is presented. In this new formulation, the theories depend only on one common parameter called ‘wave mass’, which is deduced from experiments for selected elementary particles and for the classical mass of one kilogram. It is shown that quantum theory with the wave mass is independent of the Planck constant and that higher accuracy of performing calculations can be attained by such theory. Natural units in connection with the presented approach are also discussed and justification beyond dimensional analysis is given for the particular choice of such units.
Spectral characteristics of coupled resonators

In devices consisting of a large number of coupled resonators, the coupling coefficients are unlikely to be identical throughout the ensemble, owing to statistical fluctuations in the fabrication process, the surrounding environment, or the device operation process. We describe how the frequency spectrum of such a disordered device differs from that of earlier models that assume a perfectly ordered lattice of resonant elements. Based on simulations for a large number of nominally identical resonators perturbed by disorder in the coupling coefficients, we describe the change in the density of modes (resonances) using both Hermitian and non-Hermitian coupling pathways, following recent experimental demonstrations. The band-edge zero-group-velocity state is highly sensitive to disorder, and applications that rely on band-edge effects, such as ultraslow light and group-velocity dispersion compensation, may be strongly impacted.
Cysteamine: a Potent and Specific Depletor of Pituitary Prolactin

Cysteamine rapidly reduces the concentration of prolactin in pituitary tissue in vivo and in vitro. The effect is dose-dependent, reversible, and cannot be accounted for by prolactin release. Cysteamine does not appear to exert its effect through dopamine receptors and does not alter lactotrope morphology, as determined by electron microscopy.
MAPPING THE STELLAR BACKBONES OF SPIRAL GALAXIES

We present optical and IR surface photometry of M51 (NGC 5194) at B, V, R, I, J, K, and CO. These data are used to establish whether K-band images of spiral galaxies provide reliable maps of stellar surface mass density features such as massive spiral arms or bars. The main distorting agents in the mapping at shorter wavelengths are dust extinction and luminous young stars. From modeling the color changes across the main dust lanes in M51, we find the optical depths to be about 0.5 in the K band. For these optical depths the K-band flux is attenuated by only less than 10 percent even in the dust lanes. From monitoring the gravity-sensitive CO index across the spiral arms we find that young red supergiants do not significantly distort the K-band image. On this basis, we conclude that K-band images do trace the massive disk star population and allow to map azimuthal variation in the surface mass density of the stellar disk. In M51 we find the surface mass density contrast to range from 1.8 to 3, as expected from N-body simulations of the galaxy's tidal encounter with NGC 5195. The spiral arm amplitude in M51 clearly shows smooth, strong radial variations, with a maximum at about 130 arcsec and minima at 45 and 170 arcsec.
Epidemiology and Natural History of Psoriatic Arthritis: an UpdateWhat Dermatologists Need to Know

Psoriatic arthritis (PsA) is a chronic inflammatory disease that can be associated with permanent joint damage and disability. Because patients may be unaware of the association of joint disease with psoriasis, dermatologists play an important role in identifying PsA. In this review, we discuss the natural history and key features of PsA, the epidemiology and hypothesized risk factors for disease, and screening tools that can be used in the dermatology clinic to aid in identifying which patients should be referred to a rheumatologist for further assessment.
A synthesis of (±)-hymenin

Abstract (±)-Hymenin (1) has been synthesized by a highly efficient route involving the generation of an azafulvene intermediate and its coupling with 2-aminoimidazole.
Non-muscle α-actinins are calcium-sensitive actin-binding proteins

Many actin-binding proteins have been purified from different cell types, and a number of them share certain features: they are affected by calcium in their interaction with actin and have similar subunit molecular weights (∼100,000) on SDS-poly-acrylamide gels. These proteins have been given various names, including gelsolin1–3, villin4,5, actinogelin6,7, Dictyostelium 95K protein8,9, platelet 95K protein10 and Acanthamoeba 85K protein11. The actin-binding protein α-actinin has received little attention in this analysis, even though it has a subunit molecular weight in this range (∼100,000) and has been shown immunologically to exist in non-muscle cells12,13. Here we report that α-actinin purified from HeLa cells is inhibited from cross-linking actin filaments by micromolar free calcium. In many properties it closely resembles actinogelin, Dictyostelium 95K protein and Acanthamoeba 85K protein, but it appears distinct from proteins such as gelsolin and villin which, in the presence of calcium, fragment actin filaments into short oligomers3,5. We conclude that in this molecular weight range there are at least two classes of non-muscle actin-binding protein: one corresponding to non-muscle α-actinins and the other to proteins such as gelsolin and villin.
S03-05. Genetic regulation of gastrulation movements in zebrafish

Much progress has been made recently in our understanding of how genes control patterns of cell types or regional identities with in an organism during its development. However, the link between this process of patterning and growth or morphogenesis is much less well understood. Bridging this gap requires a quantitative understanding of how genes modify growth of multicellular tissues in 3D space at multiple scales. We have been addressing this problem using a combination of genetic, morphological, computational and imaging approaches in collaboration with Andrew Bangham (University of East Anglia) and Przemyslaw Prusinkiewicz (Calgary). The results provide new insights into how genes interact with patterns of growth at various scales to modify shape. The talk will illustrate how integrating biological and computational methods may lead to a quantitative mechanistic framework for development.
Conjugated linoleic acid may be useful in treating diabetes by controlling body fat and weight gain.

335 THE TERM “CONJUGATED LINOLEIC ACID” refers to a group of closely related positional and geometric conjugated dienoic isomers of linoleic acid (Fig. 1). We coined the acronym CLA when we reported that conjugated linoleic acid isolated from grilled beef, or produced by base-catalyzed isomerization of linoleic acid, was an effective inhibitor of mouse epidermal neoplasia induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene.1 This was followed by our observations that feeding CLA (0.5% of diet) to rodents or chickens protected them from the catabolic effects of immune stimulation while enhancing the immune response,2,3 reduced blood lipids and the development of atherosclerosis in rabbits fed an atherogenic diet,4 enhanced feed efficiency in young rodents indicating that it may regulate energy metabolism and nutrient partitioning,5,6 and reduced body fat gain in part by regulating the lipid content of adipocytes.6–9 These findings have been independently confirmed and expanded in different models by other investigators (for a current listing of the scientific literature on CLA since 1987, see http://www. wisc.edu/fri/clarefs.htm). Interest in possible specific applications to diabetes treatment was sparked by a report that dietary CLA reduced fasting glucose and blood insulin levels in Zucker diabetic fatty rats.10 It was proposed that CLA produced these effects by acting through peroxisome proliferator-activated receptors (PPARs) a and g. PPAR-g is of special interest in this regard as it is a key regulator of adipocyte differentiation as well as a target of thiazolidinediones (TZDs), which restore insulin sensitivity in type-2 diabetes. Accordingly, it was further proposed that CLA might mimic the biochemical effects of TZDs and hence be useful in treating type-2 diabetes in humans.10–12 While the general applicability of these observations to other species and the mechanistic relationships among the bioactive CLA isomers, PPARs, and TZDs remain unclear,6,13–15 it is nonetheless plausible that CLA might prove useful in type-2 diabetes treatment in humans via its ability to control body fat gain.
Simulation of Power Grid Networks Considering Wires and Lognormal Leakage Current Variations

As the technology scales into 90 nm and below, process-induced variations become more pronounced. In this paper, we propose an efficient stochastic method for analyzing the voltage drop variations of on-chip power grid networks, considering both wire and log-normal leakage current variations. The new analysis is based on the Hermite polynomial chaos (PC) representation of random processes. Different from the existing Hermite PC based method for power grid analysis, which considers only wire variations and model all the random variations as Gaussian processes. The new method considers both wire variations and leakage current variations. We model the variational sub-threshold leakage currents as log-normal distribution random variables. Our experiment results show that the new method is more accurate than the Gaussian-only Hermite PC method using the Taylor expansion method for analyzing leakage current variations, and two orders of magnitude faster than the Monte Carlo method with small variance errors
Effect of Basic Fibroblast Growth Factor on Myocardial Angiogenesis in Dogs With Mature Collateral Vessels

Abstract Objectives. We sought to evaluate the potential of basic fibroblast growth factor (bFGF) to enhance coronary collateral perfusion in dogs with chronic single-vessel coronary occlusion. A secondary goal was to examine whether the salutary effects of bFGF treatment, previously proved effective in the short term, would be maintained in the long term (6 months). Background. bFGF, an angiogenic growth factor, is currently the subject of a Phase I trial in patients with ischemic heart disease. It has been shown to promote collateral development in dogs with progressive coronary occlusion when given during the period of natural collateralization. The effect of bFGF on quiescent collateral vessels, a subject of significant clinical importance, is uncertain. Methods. Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF (1.74 mg/day for 7 days), a regimen previously proved effective, or to saline solution. Maximal collateral perfusion was assessed 6 months later, and the dogs were reassigned to a course of bFGF or saline solution. Collateral perfusion was reevaluated after the second treatment course. Results. At 6 months, collateral function was identical in the groups treated initially with bFGF and saline solution. The subsequent course of bFGF did not induce further collateralization. Conclusions. Although we previously demonstrated the salutary effects of this bFGF regimen in the short term (5 weeks), collateral flow in control dogs reached parity with that of bFGF-treated dogs after 6 months. bFGF did not induce further collateralization in dogs with mature collateral vessels, underscoring the priming role of ischemia for bFGF-induced collateral development. (J Am Coll Cardiol 1997;29:1102–6) © 1997 by the American College of Cardiology
Adolescent Risk Taking and Self-Reported Injuries Associated with Substance Use

Objective: To examine the incidence of adolescent substance use at the time of injury and its relation to risk-taking behavior. Method: A total of 643 male and 782 female 9th through 12th grade students at three high schools anonymously completed surveys on any injuries that had occurred in the prior 6 months associated with substance use and risk-taking behavior. Results: Males reported a higher incidence of injuries related to alcohol or other drugs than females (17.3% vs. 13%). The 17 year olds reported more injuries related to substance use than 14 or 15 year olds (20.2% vs. 14.4% and 15%, respectively). A logistic regression analysis revealed that the odds of a substance use–related injury increased approximately sixfold when adolescents reported engaging in risk-taking behavior. Conclusion: A significant portion of adolescents (approximately 15%) reported injuries associated with substance use. Adolescents who reported a history of risk-taking behaviors were much more likely to report substance use–...
Genetic interactions matter more in less-optimal environments: a Focused Review of "Phenotype uniformity in combined-stress environments has a different genetic architecture than in single-stress treatments" (Makumburage and Stapleton, 2011).

An increase in the distribution of data points indicates the presence of genetic or environmental modifiers. Mapping of the genetic control of the spread of points, the uniformity, allows us to allocate genetic difference in point distribution to adjacent, cis effects or to independently segregating, trans genetic effects. Our genetic architecture-mapping experiment elucidated the “environmental context specificity” of modifiers, the number and effect size of positive and negative alleles important for uniformity in single and combined stress, and the extent of additivity in estimated allele effects in combined stress environments. We found no alleles for low uniformity in combined stress treatments in the maize mapping population we examined. The major advances in this research area since early 2011 have been in improved methods for modeling of distributions and means and detection of important loci. Double hierarchical general linear models and, more recently, a likelihood ratio formulation have been developed to better model and estimate the genetic and environmental effects in populations. These new methods have been applied to real data sets by the method authors and we now encourage additional development of the software and wider application of the methods. We also propose that simulations of genetic regulatory network models to examine differences in uniformity and systematic exploration of models using shared simulations across communities of researchers would be constructive avenues for developing further insight into the genetic mechanisms of variation control.
Full-chip sub-threshold leakage power prediction model for sub-0.18 /spl mu/m CMOS

The driving force for the semiconductor industry growth has been the elegant scaling nature of CMOS technology. In future CMOS technology generations, supply and threshold voltages will have to continually scale to sustain performance increase, control switching power dissipation, and maintain reliability. These continual scaling requirements on supply and threshold voltages pose several technology and circuit design challenges. With threshold voltage scaling sub-threshold leakage power is expected to become a significant portion of the total power in future CMOS systems. Therefore, it becomes crucial to predict sub-threshold leakage power of such systems. In this paper, we present a subthreshold leakage power prediction model that takes into account within-die threshold voltage variation. Statistical measurements of 32-bit microprocessors in 0.18 /spl mu/m CMOS confirms the mean error of the model to be 4%. Comparisons of this model to two other existing models that do not take within-die threshold voltage variation into account are also presented.
Effects for cooperable and serializable threads

Reasoning about the correctness of multithreaded programs is complicated by the potential for unexpected interference between threads. Previous work on controlling thread interference focused on verifying race freedom and/or atomicity. Unfortunately, race freedom is insufficient to prevent unintended thread interference. The notion of atomic blocks provides more semantic guarantees, but offers limited benefits for non-atomic code and it requires bi-modal sequential/multithreaded reasoning (depending on whether code is inside or outside an atomic block).This paper proposes an alternative strategy that uses yield annotations to control thread interference, and we present an effect system for verifying the correctness of these yield annotations. The effect system guarantees that for any preemptively-scheduled execution of a well-formed program, there is a corresponding cooperative execution with equivalent behavior in which context switches happen only at yield annotations. This effect system enables cooperative reasoning: the programmer can adopt the simplifying assumption of cooperative scheduling, even though the program still executes with preemptive scheduling and/or true concurrency on multicore processors. Unlike bimodal sequential/multithreaded reasoning, cooperative reasoning can be applied to all program code.
Selective modulation of GABAergic tonic current by dopamine in the nucleus accumbens of alcohol-dependent rats.

The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Alterations in glutamatergic and GAB...
A portable microfluidic paper-based device for ELISA

This paper describes a portable, three-dimensional (3D) microfluidic paper-based analytical device (3D-µPAD) for performing enzyme-linked immunosorbent assays (ELISA). To run an ELISA, the device requires only the addition of a small drop (2 µL per test zone) of sample and six drops (75 µL in total volume) of buffer solution. All the reagents required for the analysis are stored in dry form within the device, and are dissolved in the buffer and delivered to the test zones during the assay. The innovative feature of the device, which enables the delivery of different reagents and washes to the test zones without cross contamination, is a movable strip containing the test zones that can be moved manually through the device, and stops only at specified points where the test zones come into contact with different fluidic paths that sequentially transfer (i.e., wash) the reagents into the test zones. Using rabbit IgG as a model analyte, we performed an ELISA in 43 minutes, with a detection limit of 330 pM. We also demonstrated the detection of hepatitis B surface antigen (HBsAg) in serum.
Function of the chondrocyte PI-3 kinase-Akt signaling pathway is stimulus dependent

Summary Objective The PI-3 kinase-Akt pathway plays a role in cartilage anabolic as well as catabolic processes in response to activation by insulin-like growth factor-1 (IGF-1) and the pro-inflammatory cytokines interleukin-1β (IL-1β) and oncostatin M (OSM). The goal of this study was to determine how PI-3 kinase-Akt signaling regulates these seemingly opposing functions. Design Monolayer cultures of primary human articular chondrocytes were treated with IGF-1, IL-1β, OSM, or the combination of IL-1β and OSM in time course experiments. Activation of signaling proteins and MMP production were measured by immunoblotting. Cells were pre-treated with chemical inhibitors to block mitogen activated protein (MAP) kinases, PI-3 kinase, or JAK/STAT pathway activation. Constitutively active Akt1 and Akt3 were expressed to study stimulus-independent activation of Akt. Results IGF-1, OSM, and the combination of IL-1β and OSM but not IL-1β alone, stimulated phosphorylation of Akt which was sustained longer with IGF-1. IL-1β plus OSM, but not IGF-1, increased chondrocyte MMP-13 production which was inhibited with either a general PI-3 kinase inhibitor or specific inhibition of the PI-3 kinase-γ isoform. Akt1 or Akt3 activity alone was not sufficient to increase production of MMP-13. IL-1β/OSM induced MMP-13 production required activation of the MAP kinases, JNK and p38, as well as the JAK-STAT pathway which were activated by IL-1β plus OSM but not by IGF-1. Conclusions The chondrocyte integrates signals from the PI-3 kinase-Akt pathway with signals from MAP kinases and the JAK-STAT pathway to allow for a differential response to a pro-anabolic (IGF-1) and a pro-catabolic (IL-1β plus OSM) stimulus.
An analysis of lesion size and location in newly diagnosed cytomegalovirus retinitis.

Abstract Objective To investigate the size and distribution of lesions in newly diagnosed cytomegalovirus retinitis (CMVR). Design Retrospective, observational case series. Participants Fundus photographs of 252 newly diagnosed CMVR lesions in 173 eyes of 130 patients (123 male, 7 female). Methods Thirty-five millimeter (60°) color transparencies were digitized. A montage of the retina was assembled for each involved eye and was superimposed on a specially designed map of the postequatorial retina. Cytomegalovius retinitis lesions were delineated, and the size and location of each lesion was measured. The size of newly diagnosed CMVR lesions was computed in terms of percent postequatorial retinal surface area (PERSA), and the location of lesions was plotted on a polar coordinate system. Main outcome measures Size and location of patches of newly diagnosed CMVR. Results The median lesion size was 3% PERSA. Peripheral CMVR lesions were larger than posterior ones ( P P = 0.27). The concentric distribution of lesion centers appeared to be homogeneous, except for fewer centers in the most peripheral 14° ( P P P = 0.003). Conclusions Most newly diagnosed CMVR lesions were small. Peripheral lesions were larger than more posterior lesions. Variations from a homogeneous distribution of lesions were noted only at the extreme peripheral and central locations and are probably explained by ascertainment bias. The macula was not spared from new CMVR lesions in this patient population.
Acoustic playback experiments to study behavioral responses of free-ranging marine animals to anthropogenic sound

Growing concern about the effects of anthropogenic sound on marine life has high- lighted the need for empirical methods to study behavioral responses of marine animals to specific acoustic exposures. Some effects have been discovered by observing coincidence of effects with sound exposure, e.g. beaked whales such as Ziphius cavirostris and Mesoplodon densirostris may mass strand during sonar exercises. Sometimes new activities trigger precautionary concern, such as the potential effects of deep water seismic surveys on deep-diving endangered species, e.g. sperm whales Physeter macrocephalus. In both cases, the best way to prove that a particular sound stimulus causes a behavioral response involves experiments whereby a specific dose of sound is broadcast to an animal and the acoustic exposure and behavioral responses of the animal are measured. The pre- sent paper argues for a balance of experimental and observational studies of effects of sound on marine life, designed so that each kind of study complements the other.
FETAL DIAGNOSIS AND MANAGEMENT OF CONGENITAL HEART DISEASE

Fetal echocardiography has had a significant impact on the diagnosis and management of congenital heart disease. Although the fetal circulation is quite forgiving for many heart lesions, other flow abnormalities gravely affect fetal physiology. Serial studies have given us a window to observe the natural history of many lesions that progress during gestation. Although fetal cardiac surgery is not yet a viable alternative to neonatal repair, fetal intervention on noncardiac disorders has had limited success and the field is growing. Fetal diagnosis remains an integral part of the management of children with cardiac lesions.
Electrokinetic Dispersion in Capillary Electrophoresis

A “Taylor” dispersion-type model is developed for the electrokinetic dispersion coefficient of a solute in capillary electrophoresis that accounts for the effects of Poiseuille and/or electro-osmotic flow of the elutant for the case of low ζ potential. The expression obtained for the height equivalent of a theoretical plate is compared with experimental results reported in the literature for the case of neutral, nonretained solutes propelled by electro-osmotic flow. The results further reveal some interesting and somewhat unexpected interactions of the electro-osmotic and Poiseuille components of the elutant flow. Superposition of Poiseuille flow on the natural electro-osmotic flow allows greater freedom in the choice of elutant velocity, without necessarily increasing the dispersion. In fact, it results in lower dispersion under some conditions. Optimum flow conditions are obtained for minimizing the plate height or, equivalently, for maximizing the Peclet number.
Maternal smoking during pregnancy and offspring brain structure and function: review and agenda for future research.

Introduction: Maternal smoking during pregnancy (MSDP) has been associated with long-term neurobehavioral and cognitive defi cits in offspring. Animal models demonstrate alterations in brain structure and function following prenatal nicotine exposure. However, few studies have assessed the relationship between MSDP and brain development in humans. Therefore, the aims of this review are (a) to synthesize findings from the small number of human studies investigating effects of MSDP on offspring brain development and (b) to outline an agenda for future research in this nascent area. Methods: We searched MEDLINE and Psychinfo databases for human studies of MSDP and offspring brain structure and/or function. Results: Eleven studies meeting our search criteria were identified; 6 studies investigated effects of MSDP on brain structure; 5 examined effects on brain function. Across studies, MSDP was associated with decreased volume/thickness of the cerebellum and corpus callosum, increased auditory brainstem responses, and lack of coordination across brain regions during information and auditory processing. Conclusions: Results from the small number of human studies revealed effects of MSDP on brain structure and function, highlighting potential neural pathways linking MSDP and offspring neurobehavioral and cognitive deficits. Given the limited amount of research in this area, we propose an agenda for future research. Gold standard studies would utilize longitudinal designs, integrated biological and maternal report measures of MSDP, and repeated measures of brain structure/function and neurobehavioral deficits across key developmental periods.
Self-monitoring, honesty, and cue use on Facebook: The relationship with user extraversion and conscientiousness

The present study explored the relationship between Facebook (FB) users' self-monitoring and self-reported FB honesty and the content of users' profiles. It was anticipated that high self-monitors would construct a more extraverted profile and honest FB users would construct a more conscientious profile. A content analysis of 53 cues on participants' FB profiles (N=100) was conducted. Supporting evidence was shown in a lens model analysis of FB user profiles and strangers' (N=35) impressions of users' personality. User self-monitoring was uniquely associated with three FB cues: posting a profile picture at a younger age, posting more frequently, and using more shorthand in status updates. These three cues informed strangers' estimations of user extraversion, but were unrelated to estimations of users' conscientiousness. Honesty on FB was uniquely associated with three cues that informed strangers' estimations of user conscientiousness: expressing positive affect and talking more about family in status updates, and having FB friends who expressed support in response to status updates. This study demonstrated that FB use and profile page construction were associated with FB users' personality, and the construction of profiles affected strangers' perceptions of FB users.
Intervening processes in the relationship between unemployment and health

A considerable amount of research documents the negative effects of job loss on both physical and mental health. Yet we know comparatively little about the mechanisms through which these effects occur. Unemployment, like other events, is not the same experience for everyone exposed to it. An understanding of this variation might be facilitated by breaking down the analysis of unemployment into a consideration of the various stresses that it creates or exacerbates. This is our purpose in the present paper. We demonstrate that, for one area of the United States, the effect of job loss on several health outcomes involves two mechanisms: (1) unemployment results in increased financial strain which, in turn, results in negative health effects, and (2) unemployment leaves the individual more vulnerable to the impact of unrelated life events. Controlling for financial strain, unemployed people in our sample who have not experienced an additional life event in the previous year are in no worse health than the stably employed. This provides useful insights into the nature of the unemployment experience in this particular setting. It also provides a basis for future detailed explorations of the various ways people cope with this event.
The PARSEC benchmark suite: characterization and architectural implications

This paper presents and characterizes the Princeton Application Repository for Shared-Memory Computers (PARSEC), a benchmark suite for studies of Chip-Multiprocessors (CMPs). Previous available benchmarks for multiprocessors have focused on high-performance computing applications and used a limited number of synchronization methods. PARSEC includes emerging applications in recognition, mining and synthesis (RMS) as well as systems applications which mimic large-scale multithreaded commercial programs. Our characterization shows that the benchmark suite covers a wide spectrum of working sets, locality, data sharing, synchronization and off-chip traffic. The benchmark suite has been made available to the public.
Contribution of cytochrome P-450 4A1 and 4A2 to vascular 20-hydroxyeicosatetraenoic acid synthesis in rat kidneys

20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active cytochrome P-450 (CYP) metabolite of arachidonic acid in the rat kidney, can be catalyzed by CYP4A isoforms including CYP4A1, CYP4A...
Neuroprotective potential of erythropoietin in neonates; design of a randomized trial

In 2013, nearly four million babies were born in the U.S., among whom 447,875 were born preterm. Approximately 30,000 of these infants were born before 28 weeks of gestation. These infants, termed Extremely Low Gestational Age Neonates (ELGANs), experience high morbidity and mortality despite modern therapies: approximately 20 % of ELGANs admitted to an NICU die before discharge, 20 % of survivors have severe, and 20 % moderate neurodevelopmental impairment (NDI). New approaches are needed to improve neonatal outcomes. Recombinant erythropoietin (Epo) is a promising neuroprotective agent that is widely available, affordable, and has been used safely in neonates to stimulate erythropoiesis. There are extensive preclinical data to support its use as a neuroprotective intervention: Epo promotes normal brain maturation by increasing neurogenesis, angiogenesis, and by protecting oligodendrocytes. Epo also decreases acute brain injury following hypoxia ischemia by decreasing inflammation, oxidative and excitotoxic injury, resulting in decreased apoptosis. Despite the availability of both preclinical and safety data there has not been a definitive clinical evaluation of the benefit of Epo, and a large phase III trial is necessary to provide evidence to support potential changes in practice guidelines. We first review the preclinical data motivating further clinical trials, and then describe in detail the design of the PENUT study (Preterm Epo Neuroprotection). PENUT is a phase III study evaluating the effect of neonatal Epo treatment on the combined outcome of death or severe NDI among ELGANS. 940 subjects will be randomized to determine: 1) whether Epo decreases the combined outcome of death or NDI at 22–26 months corrected age; 2) the safety of high dose Epo administration to ELGANs; 3) whether Epo treatment decreases serial measures of circulating inflammatory mediators, and improves biomarkers of brain injury; and 4) whether Epo treatment improves brain structure at 36 weeks postmenstrual age as measured by MRI. Epo neuroprotection is an exciting new approach to preterm neuroprotection, and if efficacious, will provide a much-needed therapy for this group of vulnerable infants.
Regulation of xanthine dehydrogenase and purine nucleoside phosphorylase levels in chick liver.

A number of agents which have been shown to affect the levels of xanthine dehydrogenase (XDH) and purine nucleoside phosphorylase (PNP) (EC 2.4.2.1) in the liver of the chick are listed in Table I. We have divided these agents into four groups depending upon which enzymes are affected coordinately. Group A agents induce increases in the levels of XDH, PNP and probably other enzymes involved in purine synthesis. So far Group B agents appear to specifically act on XDH, although studies of other enzymes may reveal additional effects. Group C contains representative steroid hormones which induce or suppress levels of XDH and in one case (hydrocortisone) induces an increase in tyrosine transaminase. Group D contains unsaturated fatty acids including oleic, linoleic and linolenic acids. These agents suppress levels of XDH and PNP.
Iatrogenic, Congenic, and Transgenic Models of Hypertension

Human essential hypertension is a multifactorial and complex disease involving several genes that have, thus far, defied complete characterization. Congenic models such as the spontaneously hypertensive stroke-prone rats are genetically homogeneous and thus aid the search for causative genes. The identification of quantitative trait loci (QTL) responsible for blood pressure regulation by genome-wide scanning is most commonly employed;1 however, the identification of a QTL is just the first step to identify the gene(s) of interest. Congenic strains must be produced to verify the QTL and identify the chromosomal region that must then be reduced to an appropriate size for positional cloning of the gene(s). So-called “speed congenic strategies” have been used to confirm blood pressure QTLs on rat chromosome 2.2
Plasmids as Vectors for Gene Cloning

A variety of plasmid elements have been developed for the cloning of genes in the bacterium Escherichia coli (1–5). Many of these plasmids are derivatives of colicinogenic plasmid El (ColE1) or plasmids closely related to ColEl. ColE1 is a relatively low molecular weight plasmid, naturally occurring in E. coli, that specifies the production of antibiotically active protein, colicin El, and conveys to cells harboring the plasmid immunity to this colicin. The ColE1 plasmid, while effective as a cloning vehicle in E. coli, is not maintained stably in gram-negative bacteria distantly related to E. coli and, therefore, is likely to be of limited use in agriculturally important bacteria not closely related to E. coli. This review will consider certain basic aspects of gene cloning in E. coli and the development of plasmid cloning vehicles for bacteria distantly related to E. coli. Brief consideration also will be given to the possibility of establishing gene cloning systems in plant cells.
Responding to Welfare Privatization: New Tools for a New Age

Privatization of the operation of public benefit programs in the wake of welfare reform has diminished the effectiveness of traditional approaches to advocacy. A case study from New York City of how private contractors succeeded in reducing welfare roles while imposing punitive policies on poor families offers a glimpse of possible new advocacy tools. Requiring contract-monitoring bodies that involve community members and advocates could help facilitate transparent contracting processes and reshape social welfare programs to serve clients.
Population Structure During the Demise of the Moche (550-850 AD) Comparative Phenetic Analyses of Tooth Trait Data from San José de Moro, Perú

Population structure analyses and biodistance comparisons for Middle Moche (550–700 AD), Late Moche (700–850 AD), and Transitional (850–950 AD) period skeletal samples from San Jose de Moro with a previously reported Middle Moche period sample from Pacatnamu, a nearby Jequetepeque Valley site, and eight samples from Huaca de la Luna and Cerro Oreja, two sites in the Moche Valley, suggest that substantial levels of extralocal gene flow into the Jequetepeque Valley from the adjacent highlands to the east occurred during the demise of the Moche polity there. This process strongly corresponds to evidence for a temporal increase in exotic grave offerings at San Jose de Moro during the Late Moche and subsequent Transitional periods. The broader implications of these results for our understanding of the demise of the Moche are discussed.
Rapid Detection of Escherichia coli O157 and Shiga Toxins by Lateral Flow Immunoassays

Shiga toxin-producing Escherichia coli O157:H7 (STEC) cause food-borne illness that may be fatal. STEC strains enumerate two types of potent Shiga toxins (Stx1 and Stx2) that are responsible for causing diseases. It is important to detect the E. coli O157 and Shiga toxins in food to prevent outbreak of diseases. We describe the development of two multi-analyte antibody-based lateral flow immunoassays (LFIA); one for the detection of Stx1 and Stx2 and one for the detection of E. coli O157 that may be used simultaneously to detect pathogenic E. coli O157:H7. The LFIA strips were developed by conjugating nano colloidal gold particles with monoclonal antibodies against Stx1 and Stx2 and anti-lipid A antibodies to capture Shiga toxins and O157 antigen, respectively. Our results indicate that the LFIA for Stx is highly specific and detected Stx1 and Stx2 within three hours of induction of STEC with ciprofloxacin at 37 °C. The limit of detection for E. coli O157 LFIA was found to be 105 CFU/mL in ground beef spiked with the pathogen. The LFIAs are rapid, accurate and easy to use and do not require sophisticated equipment or trained personnel. Following the assay, colored bands on the membrane develop for end-point detection. The LFIAs may be used for screening STEC in food and the environment.
Observations on the Agriculture of Argentina

THE intent of what follows is to report, especially to the agricultural economists of North America, on matters pertinent and significant to them concerning the agriculture of Argentina, insofar as such a report is likely to be worthwhile after a period of only three months of exploration by the writer.' Argentina, except for being on the other side of the equator from the United States and Canada, is as much like these countries as one can really expect any large countries on the varied earth's surface to be. It is moreover a country like them with considerable dependence on export markets for farm products. Argentina's major agricultural exports before the second world war, and in 1950-55 (excluding the drought year 1952) averaged as follows in millions of pesos per year:
Is American Nationalism Changing? Implications for Foreign Policy

This article analyzes the degree of popular consensus about a nation's identity, core values, and mission as a source of social integration and a broad constraint on foreign policy-making. It identifies cosmopolitan liberalism, nativism, and multiculturalism as three rival ideologies of American nationalism, comparing their main principles and competing approaches toward integrating a diverse society. The paper presents a synthesis of recent survey evidence to assess the relative degree of support for these competing conceptions of American identity. The relationship of these conceptions to the foreign policy orientations delineated in the Wittkopf-Holsti-Rosenau typology is examined to speculate about how shifts in American nationalism may shape the general direction of foreign policy in the future.
Abstract 3971: Pericardial Fat is more Strongly Associated with Calcified Coronary Plaque than Body Mass Index or Waist Circumference

Pericardial fat has a higher secretion of inflammatory cytokines than subcutaneous fat. It has been suggested that cytokines released from pericardial fat around coronary arteries act locally on the adjacent cells. Epidemiologic studies of the association between pericardial fat and coronary heart disease are still lacking. Hypothesis: We hypothesized that pericardial fat would be more strongly associated with coronary atherosclerosis than other adiposity measures. Methods: Participants in the community-based Multi-Ethnic Study of Atherosclerosis underwent a computed tomography scan for the assessment of calcified coronary plaque in 2001/02. We measured the volume of pericardial fat using these scans in 159 participants without symptomatic coronary heart disease from Forsyth County, NC, aged 55–74 years, randomly selecting 40 from each gender and ethnic (white and black) group. Results: Compared to the participants without the presence of calcified coronary plaque, those with the presence of calcified coronary plaque (N=91) had a greater volume of pericardial fat (Mean (SD): 99.6 (51) vs 72.2 (34) cm 3 ; p 0.1). On the other hand, body mass index and height-adjusted waist circumference were not associated with calcified coronary plaque. Conclusions: In conclusion, pericardial fat is more strongly associated with calcified coronary plaque than body mass index or waist circumference.
[Economic evaluation of the use of diclofenac/misoprostol in the treatment of osteoarticular diseases].

OBJECTIVE To carry out a economic evaluation of diclofenac/misoprostol in the treatment of rheumatoid arthritis and osteoartritis when comparing with diclofenac alone, diclofenac + omeprazol, and diclofenac + ranitidine. DESIGN Cost effectiveness analysis using a decision analytic model, where the effectiveness unit was defined as the patient free of gastro-intestinal toxicity. MATERIAL AND METHODS The effectiveness data of the four alternatives under evaluation have been obtaining from published clinical trials. In this analysis only direct medical costs have been included without incorporating indirect costs or intangible costs. The perspective chosen has been a primary care area and the time horizon 6 months. All costs are expressed in monetary units of 1998. MEASUREMENTS AND RESULTS The cost/effectiveness ratio obtained with diclofenac/misoprostol has been a 37% lower compared with diclofenac alone (42,238 vs 67,214 ptas), a 39% compared with diclofenac + omeprazol (42,238 vs 69,058 ptas) and a 50% compared with diclofenac + ranitidine (42,238 vs 85,198 ptas). The sensitivity analysis performed has shown that diclofenac/misoprostol is the therapeutic alternative more efficient even when most influential variables are modified. CONCLUSIONS Diclofenac/misoprostol has demonstrated to be an alternative with a better cost/effectiveness ratio, and therefore more efficient than diclofenac alone or the concomitant use of diclofenac either with omeprazol or ranitidine. The routinary use of this association will save important resources to the National Health Service.
Abstract 3829: Preclinical development of a combination inhibitor strategy to block K-Ras effector signaling and autophagy for pancreatic cancer treatment

Pancreatic cancer is the 4th leading cause of cancer deaths in the US and the 5-year survival rate is a dismal 6%. The KRAS oncogene is mutated in ∼95% of pancreatic ductal adenocarcinoma (PDAC) and targeting KRAS is one of four key priorities for pancreatic cancer research, as outlined by the NCI. We hypothesize that inhibition of K-Ras effector signaling is the most promising approach to achieve this goal, and that concurrent inhibition of mutant KRAS-mediated metabolic reprogramming, in particular upregulated autophagy, is needed to disrupt resistance mechanisms that render PDAC cells unaffected by inhibition of either pathway alone. Our preliminary data show that PDAC cells increase levels of autophagic signaling upon KRAS silencing as a compensatory mechanism for the cell to maintain anabolic processes, particularly due to the loss of upregulated glycolytic signaling and macropincytotic scavenging. Furthermore, we show that ERK inhibitor treatment, just like KRAS silencing, increases autophagic flux in PDAC cells. Additionally, we have demonstrated in vitro that chloroquine (CQ), an inhibitor of autophagy, synergistically enhances the anti-proliferative capacity of two different ERK inhibitors, one of which is under clinical evaluation. Finally, we show that signaling pathways that promote resistance to ERK inhibitor treatment alone are incapable of promoting resistance to the combination treatment with CQ. Overall, our studies support the further clinical evaluation of duel ERK and autophagy inhibition as a treatment for PDAC. Citation Format: Kirsten L. Bryant, Tikvah K. Hayes, Daniel Zeitouni, Samuel D. George, Swapnil Kher, Ahmed A. Samatar, Kris C. Wood, Alec C. Kimmelman, Channing J. Der. Preclinical development of a combination inhibitor strategy to block K-Ras effector signaling and autophagy for pancreatic cancer treatment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3829.