cssi/SciSciGPT-SciSciNet huggingface dataset:
Polycystic ovary syndrome: a risk for coronary artery disease?

Abstract Objective: The purpose of this study was to evaluate the literature that was pertinent to cardiovascular risk in women with the polycystic ovary syndrome. Study Design: Medline , Current Contents , and Pub-Med were searched for human studies from the time of our original interest in this issue in 1975 to the present. Only pivotal articles are presented because of page constraints and reference number limits. Results: Current literature supports the fact that women with this syndrome have risk factors for premature cardiovascular disease. Conclusion: Large multisite cooperative studies are necessary to evaluate cardiovascular morbidity and mortality rates from this syndrome. (Am J Obstet Gynecol 2002;186:35-43.)
Topology Selection for Signal Change Detection in Sensor Networks: RBF vs MLP

This paper documents the results of experimental simulations designed to compare the performance of multilayer perceptron (MLP) and radial basis function (RBF) based sensor signal change detection systems. The two systems are simultaneously executed in parallel on the same input signals. Both systems share an identical implementation with the exception of the activation function used in the hidden layers of the artificial neural networks. Previous experiments have employed only Multilayer Perceptrons with sigmoidal activation functions. The results of these experiments quantitatively show the advantages and disadvantages of Radial Basis neural activation for both the function prediction and function correlation neural networks tested.
DES CENDRES DE SAINT-PIERRE AU CAHIER DE CÉSAIRE

Le propos est ici de montrer que l'ecriture de Cesaire s'inspire non pas d'une representation archetypale du volcan mais du volcanisme tel qu'il se manifeste aux Antilles et d'un evenement specifique, l'eruption de la Montagne Pelee qui detruisit Saint-Pierre de la Martinique en 1902. Pour ce faire, l'A. analyse la structure du Cahier et les images evoquant une activite volcanique, avant de s'interesser au style de Cesaire, de degager enfin un parallele entre le volcan antillais et, d'une part la redaction du document, d'autre part, la personnalite du poete.
DISTRIBUTION AND PREVALENCE OF MOSQUITO-BORNE DISEASES IN O’AHU ’ELEPAIO

Abstract ABSTRACT The endemic Hawaiian avifauna is one of the most imperiled on earth, and diseases have been one of the most serious causes of species declines. From 1995–2005, we mist-netted and banded 266 endangered O’ahu ’Elepaio (Chasiempis sandwichensis ibidis) from 27 sites, examined them for visible symptoms of avian pox virus (Poxvirus avium), and screened blood samples for avian malaria (Plasmodium relictum). Pox-like lesions and malaria were found in all ’Elepaio populations on O’ahu; no parts of the island were free of these mosquito-borne diseases. Each year, 20% ± 4% of ’Elepaio had active lesions likely caused by pox and an additional 16% ± 4% had deformities and missing toes indicative of healed pox lesions. Prevalence of malaria was 87% over all years combined. Pox prevalence varied among years and was associated with annual rainfall, presumably due to greater abundance of mosquito breeding sites in wet years. Rainfall amounts at least as high as those associated with pox epizootics in 19...
Predicting Summer Arctic Sea Ice Concentration Intraseasonal Variability Using a Vector Autoregressive Model

AbstractRecent Arctic sea ice changes have important societal and economic impacts and may lead to adverse effects on the Arctic ecosystem, weather, and climate. Understanding the predictability of Arctic sea ice melting is thus an important task. A vector autoregressive (VAR) model is evaluated for predicting the summertime (May–September) daily Arctic sea ice concentration on the intraseasonal time scale, using only the daily sea ice data and without direct information of the atmosphere and ocean. The intraseasonal forecast skill of Arctic sea ice is assessed using the 1979–2012 satellite data. The cross-validated forecast skill of the VAR model is found to be superior to both the anomaly persistence and damped anomaly persistence at lead times of ~20–60 days, especially over northern Eurasian marginal seas and the Beaufort Sea. The daily forecast of ice concentration also leads to predictions of ice-free dates and September mean sea ice extent. In addition to capturing the general seasonal melt of sea ...
Self-assembly of a 5-fluorouracil-dipeptide hydrogel

The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported. The rate of release of 5-Fu from the conjugates was highly dependent on concentration in solution, whereas, release from the fully formed hydrogels was significantly slower. The 5-Fu conjugate also exhibited promising in vitro cytotoxicity against human tumor cell lines A549, H460 and H23.
Statistics of the three-dimensional ferromagnet: I. The variational method*)

Synopsis The variational method developed by Kramers and Wannier is applied to the I s i n g model of a simple cubic ferromagnet and in this way equations are derived from which the approximate values of the partition function and thus of the configurational energy and specific heat can be obtained. These equations are solved both by series expansions and by numerical methods at temperatures above the Curie temperature.
Dinitrogen Fixation Associated with Sporophores of Fomitopsis Pinicola, Fomes Fomentarius, and Echinodontium Tinctorium

SUMMARYFixation of atmospheric dinitrogen by bacteria associated with contextual tissues of sporophores of Fomitopsis pinicola, Fomes fomentarius, and Echinodontium tinctorium is reported. Since ni...
Distribution and rate of disposition of myanesin in dogs.

Summary1. From a study of plasma concentrations of animals infused continuously, it has been shown that dogs can dispose of between 1 and 2 mg of myanesin per kg per minute, irrespective of plasma concentration between the limits of 50 and 130 μg per ml. 2. The rapid disposition of myanesin is due primarily to metabolic alteration. 3. Myanesin is widely distributed in the body approximately according to water content. A notable exception to this is found in the brain where tissue/plasma ratios of greater than 2 are observed.
Before Hospice: Florence Wald at the Yale School of Nursing

Analysis of Florence Schorske's Wald's professional work at the Yale School of Nursing before she brought hospice to the United States shows the same value-based dedication to innovation that later characterized her work in death and dying.
Anxiety and Depression in Substance Abuse: Clinical Implications

Accurate diagnosis in patients presenting with anxiety and/or depressive symptoms requires that the contribution of substance abuse be carefully considered. When chemical dependence is identified, detoxification may be all that is necessary. However, if indicated, specific treatment of the mood or anxiety disorder may reduce substance use as well.
Dens in dente

Abstract From the foregoing discussion and case findings, it is seen that dens in dente is a very interesting dental anomaly. The purpose of this article is to make the general practitioner cognizant of the fact that this condition does exist and that it can affect clinical dentistry.
Spatial ecology of coyotes in the Denver metropolitan area: influence of the urban matrix

Urbanization alters landscapes and ecosystem processes that result in negative impacts for many species. However, urbanization also creates novel environments that certain species, including carnivores, are able to exploit. Coyotes ( Canis latrans ) are 1 example of a species capable of exploiting urban environments throughout North America and, in some cases, becoming involved in human–coyote conflict. As part of a comprehensive study of human–coyote coexistence in the Denver metropolitan area of Colorado, we investigated the spatial ecology of coyotes to determine movement and activity patterns relative to the urban matrix. We examined home-range size, habitat use, and resource selection for 22 coyotes monitored with GPS collars during 2012–2014. Mean (± SD ) home-range size of resident coyotes (11.6±11.0 km2) was smaller than ranges of transient coyotes (200.7±232.4 km2). Home-range size did not vary by season or sex, but resident coyotes during the day (7.2±10.5 km2) had smaller home ranges than during the night (11.3±10.8 km2). Coyotes had high percentages of developed lands (44.5±18.9%) within their home ranges, contrary to previous studies of urban coyotes. However, the percentage of coyote locations in natural lands (48.9±22.4%) was higher than in developed lands (20.6±11.7%). Home-range size of residents was not related to either the percentage of developed lands or altered lands within home ranges. Coyotes selected natural lands over developed lands, and they increased activity at night. Although coyotes were able to thrive in home ranges containing large amounts of development, they continued to avoid areas with high human activity by primarily residing in areas with natural land cover. Similar to urban areas throughout the Northern Hemisphere, coyotes in the Denver metropolitan area have become efficiently adapted to a highly developed landscape, reflecting the flexible nature of this opportunistic carnivore.
Carcinoma of the prostate in a 25-year-old man: A case report and review of the literature

AbstractProstatic carcinoma in the third decade of life is a rare occurrence. We describe a 25-year-old man with prostatic cancer, as well as discuss the literature and the natural history of the disease in the young adult.
Identifying Broad and Narrow Financial Risk Factors with Convex Optimization

Factor analysis of security returns aims to decompose a return covariance matrix into systematic and specific risk components. To date, most commercially successful factor analysis has been based on fundamental models, although there is a large academic literature on statistical models. While successful in many respects, traditional statistical approaches like principal component analysis and maximum likelihood suffer from several drawbacks. These include a lack of robustness, strict assumptions on the underlying model of returns, and insensitivity to narrow factors such as industries and currencies, which affect only a small number of securities, but in an important way.We apply convex optimization methods to decompose a security return covariance matrix into low rank and sparse parts. The low rank component includes the market and other broad factors that affect most securities. The sparse component includes narrow factors and security specific effects.We measure the variance forecasting accuracy of a low rank plus sparse covariance matrix estimator on an equally weighted portfolio of 100 securities simulated from a model with two broad factors and 21 narrow factors. We find that the low rank plus sparse estimators are more accurate than estimates made with classical principal component analysis, in particular, at forecasting risk due to narrow factors. Finally, we illustrate a low rank plus sparse decomposition of an empirical covariance matrix of 100 equities drawn from 21 countries.
Benign Prostatic Hyperplasia Treatment Options and Their Effects on Sexual Function

Abstract Introduction The goal of any medical or surgical treatment for benign prostatic hyperplasia (BPH) is to improve quality of life. It is important to consider the sexual side effects of these treatments, which can directly affect quality of life. Aim To review the published literature on the sexual side effects of different medical and surgical treatments for BPH. Methods A literature review was performed of the various approved medical and surgical treatments for BPH and their respective sexual side effects. Main Outcome Measures The main outcome measure was sexual dysfunction associated with different treatments in the form of ejaculatory dysfunction, erectile dysfunction, decreased libido, and sexual dissatisfaction. Results The most common side effect for medical and surgical treatments of BPH is ejaculatory dysfunction, although its prevalence after any individual treatment varies greatly. Surgical therapies have a greater relative impact on erectile dysfunction compared with medical therapies; the exact mechanism of this erectile dysfunction has yet to be fully elucidated. The degree of decreased libido and sexual dissatisfaction associated with most treatments is poorly described in the literature and often contradictory. Conclusion There are numerous medical and surgical therapies available for treating BPH. Most of these therapies have sexual side effects that can negatively affect a patient's quality of life. It is important for physicians to consider these sexual side effects and to discuss them with their patients before initiating treatment.
Digital government: balancing risk and reward through public/private partnerships

The modern focus on the application of business principles to the running of government is unique due to an escalated emphasis on divesting the public sector of as many service provision responsibilities as possible. This divestiture is being accomplished through an array of arrangements alternatively described as privatization, contracting out, outsourcing and public/private partnerships. There are three fundamental challenges to this process: (1) defining those responsibilities which cannot and should not be turned over to the private sector, (2) ensuring that such arrangements balance both the risks and rewards between the parties involved, and (3) getting the best deal for xthe public. This chapter focuses on the second point: achieving a reasonable balance that should, if implemented successfully, result in that elusive "best deal."
An Internet-based virtual reality intervention for enhancing self-esteem in women with disabilities: Results of a feasibility study.

PURPOSE To examine the feasibility of an online self-esteem enhancement group program for women with disabilities. METHOD A sample of 19 racially and ethnically diverse, community-living women with physical disabilities, 22 to 61 years old, participated in a 7-session interactive group intervention (extending Hughes et al., 2004) in the 3-D, immersive, virtual environment of SecondLife.com, using avatars with voice and text communication. Baseline and postintervention questionnaires were administered online. Criteria for determining feasibility were (a) enrollment, (b) engagement, (c) acceptability, and (d) improvement on measures of self-esteem, depression, self-efficacy, and social support. RESULTS We attained our enrollment goal and engagement exceeded expectations. Acceptability was positive; participants gave "helpful" and "enjoyable" ratings of 3.21 and 3.27, respectively, (mean on a 1 to 4 Likert scale, where 4 = high) to 5 intervention components-session materials, group sharing and discussion, relaxation exercises, action planning, and group excursions. Significant increases from baseline to postintervention were found on the Rosenberg Self-Esteem Scale (p = .02; Cohen's d = .60) and the Center for Epidemiologic Studies Depression Scale-10 (p = .005; Cohen's d = .74), with a trend toward significance on the Generalized Self-Efficacy Scale (p = .08; Cohen's d = .42). The intervention did not significantly affect the measure of social support. IMPLICATIONS An intervention to enhance self-esteem may have a corollary benefit on depressive symptomatology. Offering psycho-educational, small group interventions using online virtual worlds shows promise for circumventing disability-related and environmental barriers to accessing mental health services experienced by women with mobility limitations, and should undergo further development and testing. (PsycINFO Database Record
Vertical Schottky barrier diodes on 3C-SiC grown on Si

Characteristics of vertical Schottky barrier diodes (SBD) fabricated on N/sup -N//sup +/ 3C-SiC grown on N/sup +/Si substrate are reported for the first time. The diodes exhibited a soft breakdown at /spl sim/85 V which, to the best of our knowledge is the highest reported breakdown voltage for 3C-SiC SBD's. The barrier height of the Pt Schottky contact was determined to be /spl sim/0.85 eV. The low forward voltage drop of as-deposited Pt SBD's (/spl sim/0.85 V at 100 A/cm/sup 2/) demonstrates that the N/sup +/SiC/N/sup +/Si heterojunction is highly conductive. The specific resistance of the heterojunction (R/sub on,HJ/) was experimentally measured and an upper bound of 8/spl times/10/sup -6/ /spl Omega/-cm/sup 2/ was obtained. R/sub on,HJ/ was also extracted by one dimensional numerical simulations to be /spl sim/8/spl times/10/sup -8/ /spl Omega/-cm/sup 2/. These low values for R/sub on,HJ/ demonstrate that vertical power device structures are feasible on 3C-SiC grown on Si. >
Fiscal Redistribution in Latin America Since the Nineteenth Century

This chapter presents the first multi-country history of how Latin American government spending and taxes have reshaped the distribution of income in the long run. We combine our new historical time series for six countries with impressive recent studies of their fiscal redistribution patterns in the twenty-first century. The rising share of social spending has not been directed strongly toward the poor. The swings in fiscal redistribution in Chilean and Argentine history have been particularly dramatic. Latin America as a whole stands out as a region with a low rate of investment in education and infrastructure, redistributing away from future generations toward pensioners. Pension commitments have locked the region’s governments into prolonged pension deficits, a strong case of historical path dependence.
Enhanced Simulations and Drug Discovery of a Muscarinic G-Protein-Coupled Receptor

G-protein-coupled receptors (GPCRs) represent primary targets of about one third of currently marketed drugs. However, GPCR drug discovery has suffered from major challenges, including the highly flexible nature of the receptors and the toxicity of agonist or antagonist drugs that are designed to bind the conserved “orthosteric” site. Here, we have performed all-atom enhanced simulations using the robust Gaussian accelerated molecular dynamics (GaMD) method to investigate the ligand-dependent structural dynamics of the M2 muscarinic GPCR. The GaMD simulations revealed distinct structural flexibility and free energy profiles that depict graded activation of the GPCR. Both dissociation and binding of an orthosteric ligand were captured in a single all-atom GPCR simulation(1). In addition, we have implemented a unique structure-based approach to design allosteric modulators as selective drug leads of the M2 muscarinic receptor. Through iterative molecular docking and experimental testing, half of our 38 computationally selected lead compounds were validated as effective allosteric modulators of the M2 receptor. Our method successfully identified both positive and negative allosteric modulators of the M2 muscarinic receptor with unprecedented chemical diversity and outstanding potential for further structure-activity relationship studies(2). This approach shall be of wide applicability for drug discovery of many other GPCRs(3).References: 1.Miao, Y., and J. A. McCammon. 2016. Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor. Proc. Natl. Acad. Sci. U. S. A. In press, DOI: 10.1073/pnas.1614538113.2.Miao, Y., D. Goldfeld, E. V. Moo, P. M. Sexton, A. Christopoulos, J. A. McCammon, and C. Valant. 2016. Accelerated structure-based design of chemically diverse allosteric modulators of a muscarinic G protein-coupled receptor. Proc. Natl. Acad. Sci. U. S. A. Early Edition, DOI:10.1073/pnas.1612353113.3.Miao, Y., and J. A. McCammon. 2016. G-protein coupled receptors: advances in simulation and drug discovery. Curr. Opin. Struct. Biol. 41:83-89.
Evolving side-channel resistant reconfigurable hardware for elliptic curve cryptography

We propose to use a genetic algorithm to evolve novel reconfigurable hardware to implement elliptic curve cryptographic combinational logic circuits. Elliptic curve cryptography offers high security-level with a short key length making it one of the most popular public-key cryptosystems. Furthermore, there are no known sub-exponential algorithms for solving the elliptic curve discrete logarithm problem. These advantages render elliptic curve cryptography attractive for incorporating in many future cryptographic applications and protocols. However, elliptic curve cryptography has proven to be vulnerable to non-invasive side-channel analysis attacks such as timing, power, visible light, electromagnetic, and acoustic analysis attacks. In this paper, we use a genetic algorithm to address this vulnerability by evolving combinational logic circuits that correctly implement elliptic curve cryptographic hardware that is also resistant to simple timing and power analysis attacks. Using a fitness function composed of multiple objectives - maximizing correctness, minimizing propagation delays and minimizing circuit size, we can generate correct combinational logic circuits resistant to non-invasive, side channel attacks. To the best of our knowledge, this is the first work to evolve a cryptography circuit using a genetic algorithm. We implement evolved circuits in hardware on a Xilinx Kintex-7 FPGA. Results reveal that the evolutionary algorithm can successfully generate correct, and side-channel resistant combinational circuits with negligible propagation delay.
60 Minutes for health: examining the feasibility and acceptability of a low-resource behavioral intervention designed to promote retention in HIV care

ABSTRACTSustained retention in HIV medical care is a key health behavior for the long-term health of people living with HIV (PLWH). Approximately 60% of PLWH in the U.S. are poorly retained in HIV care, yet to date, the few available evidence-based retention-promoting interventions are resource and time intensive to implement. The current study describes the feasibility and acceptability of a theory-based retention-promoting intervention designed to meet the needs of a busy clinical care setting. 60 Minutes for Health reflects a low-resource single-session intervention, implemented by a health educator, to PLWH who have had a recent gap in care (≥6-months) in the past 18-months. Intervention content was informed by a situated application of the Information Motivation Behavioral Skills Model and delivered using a Motivational Interviewing-based format. The intervention uses a workbook to guide a series of activities that: (1) Identify and reduce misinformation guiding HIV care attendance. (2) Enhance motiv...
Current and Novel Drugs for Management of Anemia

Anemia, defined as an abnormally low concentration of blood hemoglobin, can develop as a result of multiple different disease processes. Its association with adverse outcomes irrespective of its cause underscores the importance of anemia. Therapeutic strategies to correct anemia range from replacement of red blood cells in the form of blood transfusions to various medical interventions designed to correct the underlying pathophysiology of low blood hemoglobin level. Broadly, anemia can develop as a result of either the destruction of red blood cells, or their inadequate generation. This chapter provides a broad overview of various therapies used to treat anemia developing as a result of the inadequate generation of red blood cells.
21% versus 79%: Explaining philosophy’s gender disparities with stereotyping and identification

AbstractThis study tests the hypothesis that the perception of philosophy as a male-oriented discipline contributes to the pronounced gender disparity within the field. To assess the hypothesis, we determined the extent to which individuals view philosophy as masculine, and whether individual differences in this correspond with greater identification with philosophy. We also tested whether identification with philosophy correlated to interest in it. We discovered, first, that the more women view philosophy as masculine, the less they identify with it, and second, that the less women identify with philosophy, the less they want to major in it. Interestingly, this result does not hold for men—their viewing philosophy as masculine does not correspond to their identification with it, nor does it correlate with their likelihood of majoring in it. We also discovered that the typical student does not have a preconceived notion of philosophy as masculine; this suggests that they come to view philosophy as masculi...
Economic and emission-saving benefits of utilizing demand response and distributed renewables in microgrids

Abstract The authors present several scenarios of demand response actions based on adjustments to a building’s temperature management system in combination with renewable DER integration in microgrids. Economic benefits from $9,000 to $167,000 appear possible when implementing demand response in a microgrid of 30 to 50 additional buildings. The scenarios also demonstrate the potential emission-saving effects of demand response at the grid level.
Polymorphism controls the degree of charge transfer in a molecularly doped semiconducting polymer

When an organic semiconductor (OSC) is blended with an electron acceptor molecule that can act as a p-type dopant, there should ideally be complete (integer) transfer of charge from the OSC to the dopant. However, some dopant–OSC blends instead form charge transfer complexes (CTCs), characterized by fractional charge transfer (CT) and strong orbital hybridization between the two molecules. Fractional CT doping does not efficiently generate free charge carriers, but it is unclear what conditions lead to incomplete charge transfer. Here we show that by modifying film processing conditions in the semiconductor–dopant couple poly(3-hexylthiophene):2,3,5,6-tetrafluoro-7,7,8,8,-tetracyanoquinodimethane (P3HT:F4TCNQ), we can selectively obtain nearly pure integer or fractional CT phases. Fractional CT films show electrical conductivities approximately 2 orders of magnitude lower than corresponding integer CT films, and remarkably different optical absorption spectra. Grazing incidence wide-angle X-ray diffraction (GIXD) reveals that fractional CT films display an unusually dense and well-ordered crystal structure. These films show lower paracrystallinity and shorter lamellar and π-stacking distances than undoped films processed under similar conditions. Using plane-wave DFT we obtain a structure with unit cell parameters closely matching those observed by GIXD. This first-ever observation of both fractional and integer CT in a single OSC–dopant system demonstrates the importance of structural effects on OSC doping and opens the door to further studies.
THE ELECTRICAL CONDUCTIVITY OF POLYCRYSTALLINE OLIVINE AND PYROXENE UNDER PRESSURE

Abstract Electrical conductivity (σ) measurements on polycrystalline olivine and pyroxene were made at pressures up to 5.0 GPa and at temperatures up to 1200°C to examine the effect of grain boundaries on conduction. Values of σ were observed within one-half order of magnitude of those for single crystals at lower pressures and under controlled oxygen fugacity (fo2). if this difference prevails over the entire temperature range, these values result in temperature profiles for the earth and moon that are lower than profiles from single-crystal data by no more than 200°C. However the small σ differences between single and polycrystals most probably are due to a higher fo2 in the experimental apparatus rather than the presence of grain boundaries. The data indicate pressure has a small effect on conductivity and activation enthalpies associated with conduction.
Smart Crowdsourcing Based Content Review System (SCCRS): An Approach to Improve Trustworthiness of Online Contents

Online media is now a significant carrier for quicker and ubiquitous diffusion of information. Any user in social media can post contents, provide news blogs, and engage in debate or opinion nowadays. Most of the posted pieces of information on social media are useful while some are fallacious and insulting to others. Keeping the promise of freedom of speech and simultaneously no tolerance against hate speech often becomes a challenge for the hosting services. Some automated tools were developed for content filtering in industries. Also, companies are hiring specialized reviewers for accurate and unbiased reporting. However, these approaches are not achieving the goal as expected, on the other hand, new strategies are being adopted to tweak the automated systems. To face the situation, we proposed a smart crowdsourcing based content review technique to provide trustworthy and unbiased reviews for online shared contents. In this techniques, we designed an intelligent self-learned crowdsourcing strategy to select an appropriate set of reviewers efficiently which ensures reviewers’ diversity, availability, quality, and familiarity with the news topic. To evaluate our proposed method, we developed a mobile app similar to popular social media (e.g., Facebook).
Associations of TBI, PTSD, and depression with dementia risk among female military veterans: Not just men.

Over the past decade, it has become increasingly recognized that military veterans are at higher risk than the general population for neuropsychiatric conditions such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression.1 More recent work has shown an ≈2-fold increased long-term risk of dementia among predominantly male military veterans with TBI, PTSD, or depression2–4 compared to veterans without any neuropsychiatric conditions. However, the association of neuropsychiatric conditions with dementia among female military veterans is an important gap in the literature. More women are joining the military, and there is increasing evidence of sex differences in dementia risk in the general population.5
Abstract SY19-03: Single-cell signaling and pathology in primary cell cancers for mechanism and diagnostics

Intracellular assays of signaling systems has been limited by an inability to correlate functional subsets of cells in complex populations based on active kinase states or other nodal signaling junctions. Such correlations could be important to distinguish changes in signaling status that arise in rare cell subsets during functional activation or in disease manifestation. We have demonstrated the ability to simultaneously detect activated kinases and phosphoproteins in simultaneous pathways in subpopulations of complex cell populations by multi-parameter flow cytometric analysis, and now via high throughput mass spectrometry at the single cell level. The focus of the presentation will be our mechanistic studies of human Follicular Lymphoma, as well as signaling of “stem cell” like cell subsets in Acute Myelogenous Leukemia and other myeloid dysplasias. The detailed, correlated datasets generated via single cell phospho-flow allows for ready representation via automated signaling network determination using Bayesian analysis. Our pursuit of deep analysis of these datasets, and the limitations of cloud computing or standard multi-CPU systems, has stimulated our development of unique computational approach using field programmable gate arrays and GPU multiprocessor architectures in the development of a ‘bioinformatics supercomputer’ and associated algorithms. By analyzing the immune system, or cancer, as individual cells we now observe structured network interactions within these tissues at a new level of clarity. I will present our initial generations of comprehensive network topology maps of signaling within, and between, primary immune subsets in normal and pathologic disease tissues in cancer. My emphasis will be on the application of these approaches directly to human samples in near-patient settings for the development of point-of-care mechanistic referencing of disease and drug action. Citation Format: Garry P. Nolan. Single-cell signaling and pathology in primary cell cancers for mechanism and diagnostics [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY19-03
Distribution and morphometry of buried inlet channels along a microtidal paraglacial coast: Indispensable role of GPR

Abstract Breaching of coastal barriers, leading to the formation of ephemeral or permanent inlets, is an essential element of coastal evolution in many parts of the world. With time, some inlets migrate or close, leaving no surface signature of their existence. The challenge of locating these channels through coring is exacerbated by high gravel content and widespread anthropogenic development. Subsurface imaging using ground-penetrating radar (GPR) is often the only viable technique to overcome this limitation. GPR surveys carried out across microtidal baymouth barriers fronting salt ponds on Cape Cod, Massachusetts reveal a series of paleo-channels that lack any geomorphic expression. In some areas, channel fill comprises 50–80% of the barrier lithosome. The pre-closure dimensions of historic channels identified on charts and photographs spanning the past 170 years were measured in these subsurface records. In addition, records revealed eight previously unknown relict channel structures with widths (W) ranging between 25 and 100 m and depths (D) of 1–4 m. Based on minimum cross-sectional dimensions in GPR images, a W/D ratio of ~40 is characteristic of the natural (unstabilized) paleo-channels. This study demonstrates that the distribution and morphometry of buried channels based on high-resolution geophysical images can be used to reconstruct past equilibrium hydrodynamic conditions, with implications for locating important alongshore anomalies and assessing coastal vulnerability to breaching.
Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models

Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Induced pluripotent stem cells (iPSCs) are invaluable tools for neurological disease modeling, as they have unlimited self-renewal and differentiation capacity. Mounting evidence shows: (i) various brain cells can be generated from iPSCs in two-dimensional (2D) monolayer cultures; and (ii) further advances in 3D culture systems have led to the differentiation of iPSCs into organoids with multiple brain cell types and specific brain regions. These 3D organoids have gained widespread attention as in vitro tools to recapitulate complex features of the brain, and (iii) complex interactions between iPSC-derived brain cell types can recapitulate physiological and pathological conditions of blood-brain barrier (BBB). As iPSCs can be generated from diverse patient populations, researchers have effectively applied 2D, 3D, and BBB models to recapitulate genetically complex neurological disorders and reveal novel insights into molecular and genetic mechanisms of neurological disorders. In this review, we describe recent progress in the generation of 2D, 3D, and BBB models from iPSCs and further discuss their limitations, advantages, and future ventures. This review also covers the current status of applications of 2D, 3D, and BBB models in drug screening, precision medicine, and modeling a wide range of neurological diseases (e.g., neurodegenerative diseases, neurodevelopmental disorders, brain injury, and neuropsychiatric disorders). © 2019 American Physiological Society. Compr Physiol 9:565-611, 2019.
Particulate organic matter distributions in surface waters of the Pacific Arctic shelf during the late summer and fall season

Abstract Climate change is leading to marked decreases in the extent, thickness and persistence of sea ice in Polar Regions , especially during the later summer and fall seasons. The expanded open water domain during this period has the potential to drastically affect the hydrography, biogeochemistry and ecology of Arctic seas. In view of these rapid changes, the distributions of particulate organic matter in surface waters from the Pacific Arctic shelf were determined during the late summer and early fall months (August–October) over four different years (2012, 2015, 2016, and 2017). Utilizing surface underway systems of research vessels in combination with a semi-automated filtration system, over a thousand individual samples from surface waters were collected along the northern Bering Sea and Chukchi Sea shelves. Particulate organic carbon (POC) concentrations and molar carbon:nitrogen ratios ([C:N]) were determined to investigate the distribution and provenance of organic matter in surface waters at a high spatial resolution along the research vessels' navigational paths. Corrections for sorption of dissolved carbon and nitrogen were possible at high frequency because of our sampling techniques. The resulting blank-corrected POC concentrations in surface waters ranged from 60 μM). Large spatial and temporal variability characterized measurements throughout the study area, with maxima in POC concentration often measured in association with physical features (e.g., straits, capes, fronts, shoals) and strong wind events. Hydrographically, POC distributions displayed significant variability among water masses in the region. Alaska Coastal Water, which was predominant along the southern section of the study area (between Bering Strait and Pt. Hope), displayed the highest POC concentrations whereas Bering-Chukchi Shelf Water and especially Melt Water, which occupied the northern section of the study area (Pt. Hope to Utquiagvik) were characterized by the lowest POC concentrations. Earlier periods (August–September) also were characterized by higher average POC concentrations than later periods (September–October). Overall, most of the samples collected exhibited [C:N] ratios that ranged from 6 to 8 mol:mol, and were consistent with a predominant marine provenance. Our findings indicate POC distributions reflect patterns of wind forcing and physical circulation and identify regions of localized high standing stocks that suggest spatially and temporarily variable production in this area during the late open-water season.
Live or Virtual? Comparing Two Versions of AMP!, A Theater-Based Sexual Health Intervention for Adolescents

Theater-based approaches have been implemented globally as a health education and behavior change strategy for decades. Studies have shown that live theater performances can engage an audience and ...
If Not Now, When? US Tax Treaties With Latin America After TCJA

Since the 1990s, the US tax treaty network has expanded to include most large developing countries. However, there remains a glaring exception: The US only has two tax treaties in Latin America (Mexico and Venezuela), and one pending tax treaty (Chile). The traditional explanation for why the US has no treaty with, for example, Argentina or Brazil is the US refusal since 1957 to grant tax sparing credits to developing countries. Before the Tax Cuts and Jobs Act of 2017 (TCJA), this explanation was wrong, because the combination of deferral and cross-crediting meant that tax holidays in a source country would not lead to a shift in revenues to a residence country even without tax sparing. This traditional view needs however to be updated given TCJA. On the one hand, there is now an exemption for direct dividends, so that the traditional rationale for not entering into treaties is gone. On the other hand, GILTI means that deferral is abolished and to the extent the income of a CFC exceeds the GILTI threshold there can in fact be a transfer of revenue to the US. Nevertheless, I believe that Latin American countries should enter into treaties with the US, for three reasons. First, cross-crediting still means that even with GILTI there may not be a revenue shift. Second, there are good reasons to enter into treaties even with a revenue shift, such as attracting FDI and limiting tax evasion. Third, Latin American countries are increasingly capital exporters, and the absence of a treaty hurts their multinationals. Finally, now is an opportunity, because the entire US treaty network needs to be updated to take account of TCJA.
Large atrial septal defect misdiagnosed as arrhythmogenic right ventricular cardiomyopathy

We report on a case of a large ostium secundum atrial septal defect (ASD) that was initially diagnosed as arrhythmogenic right ventricular cardiomyopathy (ARVC). We discuss the initial work up, diagnosis, and treatment of this patient’s ASD and explore how the pathophysiology of ARVC may mimic congenital heart disease where there is a large left-to-right shunt.
Attention-deficit/hyperactivity disorder: diagnostic criteria, epidemiology, risk factors and evaluation in youth.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood with persistence into adulthood. It has a multifactorial etiology. Its chronicity, if diagnosis is missed or delayed, will result in significant negative impact on the individual’s overall functioning and development. With the revised diagnostic criteria released in 2013 by the American Psychiatric Association, established standards of clinical practice continue to be applicable and valuable in the diagnosis and management of ADHD. In older children and adolescents, it is important to differentiate what is developmentally appropriate from problematic as ADHD has high correlation with poor outcomes, comorbidities, and low quality of life.
Pathology of the Gastrointestinal Tract and Exocrine Pancreas

Xenobiotic-induced adverse effects in the alimentary system can result in a significant liability in drug development as well as after environmental exposures. Many of these adverse effects are manifested as functional disturbances such as nausea and diarrhea, but with increased exposures (dose or time), there can be morphological changes resulting in various nonneoplastic and neoplastic conditions. As the first site of exposure to ingested substances, the alimentary system serves as the first line of defense against xenobiotic exposure, and the target organs of injury or carcinogenesis depend not only on the xenobiotic but also on the animal model being used. Significant species differences in anatomy and physiology require an understanding of how these differences relate to human health risk, as well as to appropriate model selection for preclinical or hazard identification studies. This chapter will focus on the functional anatomy and physiology, background, and species-specific pathology of various species used in preclinical studies. In addition, various background and test article-related lesions in various organs in the alimentary system such as the oral cavity, salivary glands, esophagus, stomach, small and large intestine, and exocrine pancreas will be discussed. Additionally, discussion of various animal models used to study test article-related effects and recapitulate gastrointestinal disease in humans will be reviewed.
MicroRNA‐based biomarkers for diagnosis of non‐small cell lung cancer (NSCLC)

Background The development of biomarkers for the early detection of non-small cell lung cancer (NSCLC) is clinically important. We have developed miRNA biomarkers in sputum and plasma, respectively, for NSCLC. Herein, we evaluate whether integrated analysis of the miRNAs across the different types of specimens could improve the early detection of NSCLC. Methods Using reverse transcription PCR, we determined expressions of two miRNAs (miRs-31-5p and 210-3p) in sputum and three miRNAs (miRs-21-5p, 210-3p, and 486-5p) in plasma of a training cohort of 76 NSCLC patients and 72 cancer-free smokers. The results were validated in a testing cohort of 56 NSCLC patients and 55 cancer-free smokers. Results The panels of two sputum miRNAs and three plasma miRNAs had 65.8-75.0% sensitivities and 83.3-87.5% specificities for diagnosis of NSCLC in the training cohort. The individual sputum or plasma miRNA panel had a higher sensitivity for squamous cell carcinoma or adenocarcinoma of the lung, respectively. From the miRNAs, we optimized an integrated panel of biomarkers consisting of two sputum miRNAs (miRs-31-5p and 210-3p) and one plasma miRNA (miR-21-5p) that had higher sensitivity (85.5%) and specificity (91.7%) for diagnosis of NSCLC compared with the individual panels alone. Furthermore, the performance of the integrated panel of biomarkers was independent of histology and stage of NSCLC, and patients' age, sex, and ethnicity. The performance of the integrated panel of biomarkers was confirmed in the testing cohort. Conclusions Integrating biomarkers across different body fluids would synergistically improve the early detection of NSCLC. Key points Lung cancer is a heterogeneous disease and develops from complex aberrations. Integrating sputum and plasma miRNAs has higher accuracy than when they are used alone.
Do prairie voles (Microtus ochrogaster) change their activity and space use in response to domestic cat (Felis catus) excreta

Behavioral changes that reduce the risk of predation in response to predator-derived odor cues are widespread among mammalian taxa and have received a great deal of attention. Although voles of the genus Microtus are staples in the diet of many mammalian predators, including domestic cats (Felis catus), there are no previous studies on vole space utilization and activity levels in response to odor cues from domestic cats. Therefore, the objective of our study was to investigate responses of adult prairie voles (Microtus ochrogaster) living in semi-natural habitats to odor cues from domestic cat excreta. Contrary to expectations, neither adult males or females showed significant changes in space use or willingness to enter traps in response to cat odors. One hypothesis to explain our results are that prairie voles have not co-evolved with domestic cats long enough to respond to their odors. Other possible explanations include whether levels of odors in the environment were sufficient to trigger a response or that the perceived risk of predation from odor cues alone did not outweigh relative costs of changing space use and activity levels. Future studies should consider multiple factors when determining what cues are sufficient to elicit antipredatory behavior.
Bone Marrow and Adipose Tissue Adenosine Receptors Effect on Osteogenesis and Adipogenesis

Adenosine is an extracellular signaling molecule that is particularly relevant in times of cellular stress, inflammation and metabolic disturbances when the levels of the purine increase. Adenosine acts on two G-protein-coupled stimulatory and on two G-protein-coupled inhibitory receptors, which have varying expression profiles in different tissues and conditions, and have different affinities for the endogenous ligand. Studies point to significant roles of adenosine and its receptors in metabolic disease and bone health, implicating the receptors as potential therapeutic targets. This review will highlight our current understanding of the dichotomous effects of adenosine and its receptors on adipogenesis versus osteogenesis within the bone marrow to maintain bone health, as well as its relationship to obesity. Therapeutic implications will also be reviewed.