cssi/SciSciGPT-SciSciNet huggingface dataset:
Misdiagnosed as infantile hemangioma: Early presentation of small vessel-rich AVM

Abstract Arteriovenous malformations (AVMs) are typically present at birth but may not become clinically significant till later in life. The rarity of AVMs leads to misdiagnosis, as they can be confused in young patients with infantile hemangioma (IH). Small vessel-rich AVM can be radiologically consistent with an IH, while the clinical presentation is that of a slowly growing vascular anomaly. These cases highlight the clinical dilemma that while a vascular anomaly may appear by imaging studies to be the common and generally innocuous IH, an atypical growth pattern should raise clinical suspicion for an AVM.
Isolation of rat fibrillin-1 cDNA and its relevance in metanephric development.

The role of fibrillin-1 in metanephrogenesis was investigated. Fibrillin-1 cDNA was isolated from the rat kidney cDNA library and sequenced, and its spatiotemporal expression was studied. It had ∼8...
Serologic response in man to varying amounts of inactivated epidemic typhus vaccine.

SummaryThree hundred and sixty-nine Marine Corps recruits, initially without either complement fixing or toxin neutralizing epidemic typhus antibodies, were studied to determine their antibody response to subcutaneous injection of decreasing doses of commercially produced epidemic typhus vaccine administered in 1 or 2 doses of 1 ml each. When immunized with either 1 or 2 doses of undiluted vaccine or with 1 dose of vaccine diluted 1:2 or 1:4 91 to 100% of the 194 marines responded by developing either complement fixing or toxin neutralizing antibodies, or both. About 1/3 of 116 marines who received 1 dose of vaccine diluted 1:16 or 1:64 developed these antibodies. A single dose of vaccine diluted 1:256 elicited demonstrable antibodies in 15% or 9 of 59 men. These results suggested that the amount of antigen contained in 2.0 ml of vaccine required in the basic course of the immunization regimen was more than was needed to accomplish reasonable antibody responses in man. Accordingly, the primary immunizatio...
Expression of Lauroyl–Acyl Carrier Protein Thioesterase in Brassica napus Seeds Induces Pathways for Both Fatty Acid Oxidation and Biosynthesis and Implies a Set Point for Triacylglycerol Accumulation

Expression of a California bay lauroyl-acyl carrier protein thioesterase (MCTE) in developing seeds of transgenic oilseed rape alters the fatty acid composition of the mature seed, resulting in up to 60 mol% of laurate in triacylglycerols. In this study, we examined the metabolism of lauric acid and 14C-acetate in developing seeds of oilseed rape that express high levels of MCTE. Lauroyl-CoA oxidase activity but not palmitoyl-CoA oxidase activity was increased several-fold in developing seeds expressing MCTE. In addition, isocitrate lyase and malate synthase activities were six- and 30-fold higher, respectively, in high-laurate developing seeds. Control seeds incorporated 14C-acetate almost entirely into fatty acids, whereas in seeds expressing MCTE, only 50% of the label was recovered in lipids and the remainder was in a range of water-soluble components, including sucrose and malate. Together, these results indicate that the pathways for beta-oxidation and the glyoxylate cycle have been induced in seeds expressing high levels of MCTE. Although a substantial portion of the fatty acid produced in these seeds is recycled to acetyl-CoA and sucrose through the beta-oxidation and glyoxylate cycle pathways, total seed oil is not reduced. How is oil content maintained if lauric acid is inefficiently converted to triacylglycerol? The levels of acyl carrier protein and several enzymes of fatty acid synthesis were increased two- to threefold at midstage development in high-laurate seeds. These results indicate that a coordinate induction of the fatty acid synthesis pathway occurs, presumably to compensate for the lauric acid lost through beta-oxidation or for a shortage of long-chain fatty acids.
Troponin I protein kinase C phosphorylation sites and ventricular function.

Objective: Cardiac Troponin I (cTnI) phosphorylation by protein kinase C (PKC) results in a reduction of maximal actomyosin ATPase activity, an effect that is more marked at higher levels of calcium (Ca 2+ ) and is likely to reduce active force development. We postulated that there would be greater Ca 2+ -dependent changes in ventricular function in hearts of cTnI transgenic (TG) mice expressing mutant troponin I lacking PKC sites compared to wild-type (WT). Methods: We studied left ventricular function in isolated perfused hearts over a wide range of left ventricular volumes (Frank-Starling relationships) and mechanical restitution at three levels of perfusate Ca 2+ (1.5, 2.5, and 3.5 mM). Manganese-enhanced magnetic resonance imaging (MRI) was used to study in-vivo sarcolemmal Ca 2+ influx. The phosphorylation status of cTnI was examined by western blot analysis. Results: Systolic contractile function in TG mice was altered in a calcium-dependent manner such that ventricular contractility was significantly greater in TG mice only at 3.5 mM perfusate Ca 2+ . The relaxation process and passive mechanical properties were unaltered in TG mice. Mechanical restitution parameters were abnormal in TG mice only at 1.5 mM perfusate Ca 2+ . In-vivo MRI data demonstrated up to 48% reduction in Mn 2+ -induced contrast enhancement, indicating reduced sarcolemmal Ca 2+ influx. Western blot analysis indicated increased cTnI phosphorylation in TG mice. Conclusions: (1) TG mice exhibit calcium-dependent positive inotropy without slowed relaxation and this phenotype is mitigated by concomitant (compensatory) changes of reduced intracellular Ca 2+ and increased phosphorylation of remaining cTnI sites. (2) The contractile phenotype in TG mice can be interpreted as an amplification of the normal response to changes in cellular Ca 2+ observed in WT mice. Thus, PKC phosphorylation sites on cTnI play a role in attenuating contractile responses to changes in intracellular Ca 2+ .
UNSTRUCTURED NAVIER-STOKES GRID GENERATION AT CORNERS AND RIDGES

Problems related to automatic generation of highly stretched unstructured grids suitable for 3-D Reynolds-Averaged Navier-Stokes computations are addressed. Special attention is given to treatment of such geometrical irregularities as convex and concave ridges as well as corners where the ridges meet. The existing unstructured grid generation approaches may fail or produce poor quality meshes in such geometrical regions. The proposed solution is based on special meshing of non-slip body surfaces resulting in smooth and robust volume meshing and high overall quality of generated grids. Several examples demonstrate the efficiency of the method for complex 3-D geometries.
Development of the Pancreas and Pancreatic Cancer

The pancreas is specified during embryonic development from the gut endoderm. Among the signaling pathways required for the proper development of the organ are the notch and hedgehog signaling pathways. Both of these pathways are reactivated in pancreatic cancers, and sustained hedgehog signaling is required for the viability of most pancreatic cancer cell lines. Further, mouse models of the disease show activation of these pathways, and expression of pancreas progenitor markers. These findings indicate that developmentally regulated gene expression programs are important in the pathogenesis of pancreatic cancer.
On the distribution of SINR for the MMSE MIMO receiver and performance analysis

This correspondence studies the statistical distribution of the signal-to-interference-plus-noise ratio (SINR) for the minimum mean-square error (MMSE) receiver in multiple-input multiple-output (MIMO) wireless communications. The channel model is assumed to be (transmit) correlated Rayleigh flat-fading with unequal powers. The SINR can be decomposed into two independent random variables: SINR=SINR/sup ZF/+T, where SINR/sup ZF/ corresponds to the SINR for a zero-forcing (ZF) receiver and has an exact Gamma distribution. This correspondence focuses on characterizing the statistical properties of T using the results from random matrix theory. First three asymptotic moments of T are derived for uncorrelated channels and channels with equicorrelations. For general correlated channels, some limiting upper bounds for the first three moments are also provided. For uncorrelated channels and correlated channels satisfying certain conditions, it is proved that T converges to a Normal random variable. A Gamma distribution and a generalized Gamma distribution are proposed as approximations to the finite sample distribution of T. Simulations suggest that these approximate distributions can be used to estimate accurately the probability of errors even for very small dimensions (e.g., two transmit antennas).
Hemodynamics of Mechanical Circulatory Support

An increasing number of devices can provide mechanical circulatory support (MCS) to patients with acute hemodynamic compromise and chronic end-stage heart failure. These devices work by different pumping mechanisms, have various flow capacities, are inserted by different techniques, and have different sites from which blood is withdrawn and returned to the body. These factors result in different primary hemodynamic effects and secondary responses of the body. However, these are not generally taken into account when choosing a device for a particular patient or while managing a patient undergoing MCS. In this review, we discuss fundamental principles of cardiac, vascular, and pump mechanics and illustrate how they provide a broad foundation for understanding the complex interactions between the heart, vasculature, and device, and how they may help guide future research to improve patient outcomes.
Controlling Toxic Harms: The Struggle Over Dioxin Contamination in the Pulp and Paper Industry

This essay addresses the challenges of controlling toxic harms through an intensive case study of efforts to regulate and remedy dioxin contamination in the U.S. pulp and paper industry. By focusing on the struggle to control a specific toxic harm in a specific industrial sector, the essay explores the politicized nature of toxic harms in the United States and, in the process, highlights the considerable shortcomings of existing legal frameworks and institutions for dealing with problems of such scope and complexity. In doing so, the essay raises a host of normative issues regarding current institutional arrangements and the appropriate strategy for dealing with toxic harms. While both tort law and the existing regulatory system will undoubtedly have a place in efforts to deal with toxic harms, the dioxin case study demonstrates that neither has proven particularly adept at achieving the respective goals of compensation, deterrence, and pollution control in a timely and cost-effective manner. In response to such shortcomings, the essay discusses several recent innovations in environmental policy that provide a possible basis for developing a more coherent and effective approach.
Financial Impact of Postoperative Complication Following Hepato-Pancreatico-Biliary Surgery for Cancer

Despite increasing efforts for cost containment, little is known regarding the financial implications of postoperative complication under current volume-driven payment paradigms. This study sought the test the associations between hospital finances and postoperative complications among hepato-pancreatico-bilary cancer patients. Patients undergoing surgery for the management of a hepatobiliary or pancreatic cancer between January 1, 2009 and December 31, 2013 were identified using institutional claims and cost-accounting data. Multivariable linear regression analyses were used to calculate risk-adjusted fixed and variable costs, payments, and net margins. A total of 1483 met inclusion criteria. Fixed ($9290 [interquartile range (IQR) $7129–$11,598] vs. $14,784 [IQR $10,523–$22,799], p < 0.001) and variable costs ($12,342 [IQR $9886–$14,762] vs. $19,330 [IQR $13,967–$29,435], p < 0.001) were higher among patients who developed a postoperative complication following a hepatectomy. A higher contribution margin ($12,421 [IQR $8440–$16,445] vs. $20,016 [IQR $14,212–$39,179], p < 0.001), as well as a twofold higher net profit was noted among patients who developed postoperative complication ($2788 [IQR $660–$5815] vs. $5515 [IQR $1068–$10,315], p < 0.001). Total hospital costs ($26,840 [IQR $21,318–$35,358] vs. $46,628 [IQR $31,974–$69,326], p < 0.001) as well as payments ($32,761 [IQR $26,394–$41,883] vs. $53,612 [IQR $38,548–$78,116], p < 0.001) were more than 1.5 times higher among patients who developed a postoperative complication following pancreatic resection. Contribution margins ($18,356 [IQR $14,024–$24,390] vs. $29,153 [IQR $20,256–$41,785], p < 0.001), as well as net profits ($5907 [IQR $2179–$9412] vs. $8114 [IQR $2518–$14,249], p < 0.001) were higher among patients who developed postoperative complication following pancreatic surgery. A positive association was observed between net profits and postoperative complications. Future policies should target complications as a means to achieving a higher value for care.
Visualization of Kinetics: Stimulating Higher-Order Thinking via Visualization

When students are able to visualize data in real time they can think at higher levels of analysis and evaluation because the data arrive immediately. A kinetics laboratory was modified to include real-time visualization. On the basis of completion of laboratory questions, quiz, and an end-of-semester assessment, students demonstrated they could connect several disparate concepts related to kinetics.
Regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of 5,6-isopropylidene-l-ascorbic acid

An efficient regioselective synthesis of 2-O-acyl-3-O-(1-acyloxyalkyl) prodrugs of vitamin C 5,6-acetonide has been developed which does not involve tedious column chromatographic separation of the desired products from contaminants exhibiting very similar Rf values. Vitamin C 5,6-acetonide is first acylated with one equivalent of acyl halide in the presence of two equivalents of pyridine. The crude 2-O-acylated product is then alkylated with one equivalent of 1-acyloxyalkyl-1-iodide in the presence of one equivalent of triethylamine. The 2-O-acyl-3-O-(1-acyloxyalkyl) vitamin C 5,6-acetonides are obtained in moderate yields.
A New Leaf Miner Injurious to Larkspur (Phytomyza delphiniae Frost)

Both the larvae and the adults of the larkspur leaf-miner ( Phytomyzo delphiniae Frost) injure the plant. The various stages of the insect are described and notes are given on its life history and habits. Two hymenopterous parasites have been reared from the pupae: Cyrtogaster liqueatus Ashm. and a new species of Opius. Control measures are briefly discussed.
A modified bristle flowmeter for measuring phasic blood flow.

SummaryA new type of electrically recording bristle flowmeter is described, which permits measurement of volume flow of blood and its phasic changes. By recording superior vena cava flow, direct evidence is presented that the greatest acceleration of blood and a marked volume inflow into the right atrium occurs during ventricular systole, when the tricuspid valves are closed. This demonstrates the active influence of ventricular contractions on venous return.
Translational Research 2.0 – Searching for Answers in a World of Big Data

The World Wide Web has revolutionized how researchers from various disciplines collaborate throughout the world. In the Life Sciences, interdisciplinary approaches are becoming increasingly powerful as a driver of both integration and discovery. Data access, data quality, identity, and provenance are all critical ingredients to facilitate and accelerate these collaborative enterprises and it is in the area of Translational Research where Web 2.0 technologies promise to have a profound impact – enabling reproducibility, aiding in discovery, and accelerating and transforming medical and healthcare research across the healthcare ecosystem. However, integration and discovery require a consistent foundation upon which to operate. A foundation capable of addressing some of the critical issues associated with how research is conducted within the ecosystem today and how it should be conducted for the future.This paper will discuss the critical issues associated with Translational Research and their implications for future medical and healthcare research. The first set of issues concerns the enhancement of research for traditional ecosystem stakeholders, namely, research organizations and care delivery organizations, especially through the use of bio-repositories. The key questions to be addressed surrounding Translational Research 2.0 are: - What is it and how might it aid knowledge discovery and collaboration within the medical and healthcare ecosystem?- What benefits, challenges, and opportunities does it provide?- How can bio-repositories enhance it?The answers to these questions directly impact the translation of research findings from basic research, performed by research organizations, into clinical practice, provided by care delivery organizations. Finally, this paper discusses how research can be enhanced for the broader ecosystem, through the mining and analysis of knowledge surrounding health outcomes, namely: What key challenges are associated with Translational Informatics in a world of “big data”? The answer to this question is of importance to all ecosystem stakeholders, in their collective efforts to better understand health outcomes and facilitate the biomedical discovery process.
Psychopharmacological treatment of delirium: does earlier treatment and scheduled dosing improve outcomes?

PURPOSE The goals of this study were to examine how dosing strategies and timeliness of antipsychotic medication initiation would affect delirium duration. METHODS This is a retrospective paper and electronic record review of patients in an academic hospital who had been diagnosed with delirium. Forty-two patients met inclusion criteria. Quantitative and qualitative data on the course of delirium was gathered, as well as important demographic and medical variables. RESULTS There were no significant differences in duration of delirium between the scheduled and PRN groups using survival analysis, although the test was marginally significant (log rank test, p<0.06). Those who received treatment within 24 hours of recognition had significantly shorter durations of delirium compared to those who began treatment after 24 hours (log rank test, p<0.006). CONCLUSION These data suggest that early psychopharmacological treatment of delirium can reduce duration. Future research needs to investigate prompt and scheduled medication dosing strategies for treatment of delirium symptoms.
Hierarchical Crowd Curation of Very Large and Predicted Protein-Protein Interaction Data

The abundance of predicted and mined but uncertain biological data show huge needs for massive, efficient and scalable curation efforts. The human expertise warranted by any successful curation enterprize is often economically prohibitive especially for speculative end user queries that may not ultimately bear fruit. So the challenge remains in devising a low cost engine capable of delivering fast but tentative annotation and curation of a set of data items that can be authoritatively validated by experts later demanding significantly small investment. The aim thus is to make a large volume of predicted data available for use as early as possible with an acceptable degree of confidence in their accuracy while the curation continues. In this paper, we present a novel approach to annotation and curation of biological database contents using crowd computing. The technical contribution is in the identification and management of trust of mechanical turks, and support for ad hoc declarative queries, both of which are leveraged to support reliable analytics using noisy predicted interactions.
Sustaining a commitment to teaching in a research-intensive university: what we learn from award-winning faculty

ABSTRACTWithin any higher education institution, there are great teachers who recognize the challenges to sustaining a commitment to highly effective teaching. The current paper explores the beliefs and practices of 10 faculty members who won an undergraduate teacher of the year award at a research-intensive institution. The paper explores the challenges faculty face in prioritizing teaching, the strategies they use to meet these challenges, and suggests institutional supports with the potential to facilitate high-quality teaching in higher education.
Control of Neuroinflammation for Therapeutic Gain

Immunology, neuroscience and pharmacology are each independent broad multidisciplinary fields that are well developed for the biomedical sciences. The evolution of each at the molecular, biochemical and cellular levels have been, by any measure, enormous in impact by its collective abilities to change the world as we know for biomedical research. This book was fashioned to share with students and trained professionals a vision and integration for the discipline and to reach forward into its future.
Land Use Change and Human Health

Human activity is rapidly transforming our planet. The most pervasive changes to the landscape include deforestation, extension and intensification of agriculture, and livestock management, the construction of dams, irrigation projects, and roads, and rapidly spreading urbanization. In addition to the well-known environmental costs of these changes, each also has important health implications that are often less recognized. However, a growing number of studies that combine ecology and human health are demonstrating how these activities impact the emergence of new infectious diseases and alter the distribution of already recognized diseases.
Video Feedback Intervention to Enhance the Safety of Older Drivers With Cognitive Impairment

Objective To demonstrate that g-force technology can be used to help older adults with cognitive impairment improve their driving safety as part of an in-car video feedback intervention. Method Unsafe driving events triggered g-forces leading to capture of video clips. The program included 3 mo of monitoring without intervention, 3 mo of intervention (weekly written progress reports, a DVD of unsafe driving events, and weekly telephone contacts), and 3 mo of postintervention monitoring. Results Mean total unsafe driving events per 1,000 miles were reduced from baseline by 38% for 9 of 12 participants during the intervention and by 55% for 7 participants during postintervention monitoring. Mean total unsafe driving severity scores per 1,000 miles were reduced from baseline by 43% during the intervention and by 56% during postintervention monitoring. Conclusion Preliminary results suggest that driving safety among older drivers with cognitive impairment can be improved using a behavior modification approach aimed at problem behaviors detected in their natural driving environment.
Bivariate, multivariate, and matrix variate normal characterizations: A brief survey II

The paper entitled “Bivariate and Multivariate Normal Characterizations: A Brief Survey,” by Hamedani, which was published in 1992, covered the published characterizations of bivariate and multivar...
Correlating Molecular Structure to the Behavior of Linear Styrene–Butadiene Viscosity Modifiers

The effect of linear styrene–butadiene polymer structure on the temperature–viscosity behavior of model polymer-base oil solutions is investigated using molecular dynamics simulations. Simulations of alternating, random, and block styrene–butadiene polymers in a dodecane solvent are used to calculate viscosity at 40 and 100 °C, reference temperatures for characterizing their function as viscosity modifiers. Mechanisms underlying this function are explored by quantifying the radius of gyration and intramolecular interactions of the polymers at the same reference temperatures. The block styrene–butadiene configuration exhibits the least change in viscosity with temperature, characteristic of a good viscosity modifier or viscosity index improver, and the behavior is correlated to the ability of this structure to form smaller coils with more intramolecular interactions at lower temperatures and then expand as temperature is increased. The results indicate that there is a correlation between styrene–butadiene polymer structure, additive function, and the mechanisms underlying that function.
Simulated building energy demand biases resulting from the use of representative weather stations

Abstract Numerical building models are typically forced with weather data from a limited number of “representative cities” or weather stations representing different climate regions. The use of representative weather stations reduces computational costs, but often fails to capture spatial heterogeneity in weather that may be important for simulations aimed at understanding how building stocks respond to a changing climate. We quantify the potential reduction in temperature and load biases from using an increasing number of weather stations over the western U.S. Our novel approach is based on deriving temperature and load time series using incrementally more weather stations, ranging from 8 to roughly 150, to evaluate the ability to capture weather patterns across different seasons. Using 8 stations across the western U.S., one from each IECC climate zone, results in an average absolute summertime temperature bias of ∼4.0 °C with respect to a high-resolution gridded dataset. The mean absolute bias drops to ∼1.5 °C using all available weather stations. Temperature biases of this magnitude could translate to absolute summertime mean simulated load biases as high as 13.5%. Increasing the size of the domain over which biases are calculated reduces their magnitude as positive and negative biases may cancel out. Using 8 representative weather stations can lead to a 20–40% bias of peak building loads during both summer and winter, a significant error for capacity expansion planners who may use these types of simulations. Using weather stations close to population centers reduces both mean and peak load biases. This approach could be used by others designing aggregate building simulations to understand the sensitivity to their choice of weather stations used to drive the models.
Los ángeles de Lupe Pintor. Alberto Salcedo Ramos. México: Almadía, 2015

Alberto Salcedo Ramos, considerado como uno de los mejores periodistas narrativos de Latinoamerica, ha sido ganador de multiples premios, entre los cuales destacan el Premio Internacional de Periodismo Rey de Espana, el Premio Ortega y Gasset de Periodismo y dos veces el Premio a la Excelencia de la Sociedad Interamericana de Prensa.
Linear Image Approximations

This chapter presents approximations for simple calculation of CTEM and STEM (BF, ADF, and confocal) images using linear image models. A linear image is the convolution of an object function and the point spread function (multiplication in Fourier transform space). This can provide a simple intuitive approach to interpreting the electron micrographs although it might not be particularly accurate.
Training Teachers to Teach Epidemiology in Middle and High Schools.

ObjectiveThe purpose of this study was to evaluate the outcomes of a workshop which was designed to prepare teachers to teach epidemiology to middle and high school students.MethodsThe workshop int...
Superior Survival of Black Versus White Patients Following Post-Transplant Cyclophosphamide-Based Haploidentical Transplantation for Adults with Hematologic Malignancy

Abstract Available evidence from large registry studies has shown inferior survival for black adult patients following both unrelated donor and cord blood transplantation. Post-transplant cyclophosphamide (PTCy)–based haploidentical donor transplantation (HIDT) is being increasingly used in ethnic minorities. However, no studies of the impact of race on outcomes following HIDT have been reported. We analyzed 203 consecutive patients (123 white, 80 black) who underwent first HIDT using PTCy for hematologic malignancy at a single institution. Median recipient age was 53 (range, 19-75) years. Peripheral blood stem cells (PBSCs) were used as the stem cell source in 66% of patients, and conditioning intensity was myeloablative (MA) in 41%. After a median follow-up of 36 months, the estimated 3-year overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) were significantly better in black patients, compared with white patients (72% [95% confidence interval (CI), 60% to 81%], 65% [95% CI, 52% to 75%], and 25% [95% CI, 16% to 35] versus 50% [95% CI, 40% to 59%], 45% [95% CI, 36% to 54%], and 39% [95% CI, 31% to 47%], respectively; P
Net Present Value Analysis in Finance and Real Estate: A Clash of Methodologies

Executive Summary While the finance discipline focuses on the added value of a capital investment project to the firm's assets (NPVA), the real estate discipline typically looks at the impact on the firm's equity investors (NPVE). The two approaches will generate the same value provided that the project and the firm are equally leveraged. However, if the project's capital structure differs from that of the firm, NPVE will differ from NPVA. This study explores the effect of different capital structures for the project and the firm in three scenarios—a single-year project, a project generating a single cash flow multiple years into the future, and a project generating multi-year cash flows— and the resultant discrepancy between NPVE and NPVA. Using two adjustment routes, we show that NPVE can be recalculated to equal NPVA in each scenario, although the adjustment process is complicated, particularly in the more complex scenarios.
Analysis of ligand-dependent nuclear accumulation of Smads in TGF-beta signaling.

The growth inhibition of dividing cells and most of the transcriptional responses upon TGF-beta treatment depend on the Smad2, Smad3, and Smad4 transcription factors. These proteins shuttle continuously between the cytoplasm and the nucleus, transmitting the ligand status of the TGF-beta receptors to the nuclear transcription machinery. In the absence of TGF-beta ligand, Smads 2/3/4 reside predominantly in the cytoplasm. Following ligand binding to the TGF-beta receptors, the dynamic equilibrium of shuttling Smads 2/3/4 shifts towards a predominantly nuclear state, where a high concentration of these transcription factors drives transcriptional activation and repression of genes required for proper cellular response. Here, we describe live-cell imaging and immunofluorescence microscopy methods for tracking Smads subcellular localization in response to TGF-beta and leptomycin B treatment. In addition, a method of fractionating nuclear and cytoplasmic proteins used to confirm the imaging results was presented. Our results support the notion that the R-Smad shuttling mechanism is distinct from Co-Smad.
Quality Oversight in Health Care Instutitions: Monitors and Checklists

Legislative and market-driven reform initiatives are creating enormous pressures not only to improve the quality and efficiency of health care delivery in the United States but also to industrialize the structure and function of health care delivery. It is no coincidence that the health care sector is investigating and applying the tools with which manufacturing and service industries have improved their performance in changing environments. As health care as an industry moves toward full automation, it puts health organizations under pressure to interchange standards, to integrate data and to gather data on resource usage, outcomes and quality. Organizations are establishing partnerships to share the costs of collecting and integrating data.
Detecting Phishing Emails the Natural Language Way

Phishing causes billions of dollars in damage every year and poses a serious threat to the Internet economy. Email is still the most commonly used medium to launch phishing attacks [1]. In this paper, we present a comprehensive natural language based scheme to detect phishing emails using features that are invariant and fundamentally characterize phishing. Our scheme utilizes all the information present in an email, namely, the header, the links and the text in the body. Although it is obvious that a phishing email is designed to elicit an action from the intended victim, none of the existing detection schemes use this fact to identify phishing emails. Our detection protocol is designed specifically to distinguish between “actionable” and “informational” emails. To this end, we incorporate natural language techniques in phishing detection. We also utilize contextual information, when available, to detect phishing: we study the problem of phishing detection within the contextual confines of the user’s email box and demonstrate that context plays an important role in detection. To the best of our knowledge, this is the first scheme that utilizes natural language techniques and contextual information to detect phishing. We show that our scheme outperforms existing phishing detection schemes. Finally, our protocol detects phishing at the email level rather than detecting masqueraded websites. This is crucial to prevent the victim from clicking any harmful links in the email. Our implementation called PhishNet-NLP, operates between a user’s mail transfer agent (MTA) and mail user agent (MUA) and processes each arriving email for phishing attacks even before reaching the inbox.
Modulation of Leukocytes by Exotoxins Produced by HAP Organisms

The HAP group of organisms is comprised of small Gram-negative rods that can colonize the mucosal surface of the respiratory and genitourinary tracts. In some instances there is a clear relationship between a particular HAP species and its host of choice. In other cases the organism is more promiscuous and will colonize a number of host species. Depending on the HAP species involved, this colonization may be benign, resulting in little or no recognizable infection or host response in a healthy individual (Nicolet, 1990). Subsequent exposure to various types of stressors, or underlying infection with a virus or other pathogenic agent, can favor multiplication of HAP organisms that leads to clinical disease. Leukocytes provide a first line of cellular defense against invading microorganisms. As such, it is critically important for HAP organism to evade the antimicrobial activity of leukocytes if they are to multiply and cause clinical disease. HAP organisms have developed several strategies for doing this, including the production of antiphagocytic capsules and the release of exotoxins (leukotoxins) that inhibit leukocyte antimicrobial activity or kill the leukocytes (Czuprynski and Sample, 1990). More recently, it has become clear that smaller amounts of some of these leukotoxins can activate leukocytes to release oxygen radicals and other inflammatory mediators that likely contribute to the intense inflammation that characterizes many HAP infections (Czuprynski et al., 1991; Breider et al., 1991; Maheswaran et al., 1993; Udeze and Kadis, 1992). The purpose of this chapter is to provide a brief overview of these exotoxins, their relatedness among various HAP species, their differential effects on leukocyte populations, and the possible contributions of other bacterial components (i.e., lipopolysaccharide) to their biological effects.
Interactions Between Environment and Competition: How Fluctuations Mediate Coexistence and Competitive Exclusion

One of the major theoretical and empirical challenges in ecology today is elucidating the role of various kinds of heterogeneity, such as environmental fluctuations, in the dynamics of populations and the organization of communities. There is substantial evidence that stochastic environmental fluctuations have a strong role in population and community processes (Andrewartha and Birch 1954, 1984, Hutchinson 1961, Sale 1977, Connell and Sousa 1983, Sale and Douglas 1984, Grubb 1977, Wiens 1977, 1986, Murdoch 1979, Underwood and Denley 1984, Simberloff 1984, Murdoch et al 1985, Strong 1986, Victor 1986), and as a consequence, a variety of verbal theories of community structure in a stochastic environment have been developed (Hutchinson 1951, 1961, Paine and Vadas 1969, Sale 1977, Grubb 1977, Wiens 1977, Connell 1978). However, the mathematical theories of stochastic environments have not provided an adequate alternative to the classical theory based on deterministic models. There seem to be two reasons for this. First, the existing stochastic models have generally not provided the sort of simple quantitative results that often follow from deterministic models. Second, there is a widespread perception that models incorporating temporal variability may give unfathomable or inconsistent results (Hastings and Caswell 1979, Levin et al 1984). Indeed, an examination of models of communities of competitors reveals that a stochastic environment can have essentially any effect depending on the specific model involved and the assumptions that are made about it. Some models say that environmental variability promotes coexistence (Chesson and Warner 1981, Abrams 1984, Ellner 1984, Shmida and Ellner 1985), others say that environmental variability has little effect on coexistence (Turelli 1981, Chesson and Warner 1981), while others say that environmental variability promotes competitive exclusion (Chesson and Warner 1981).
Disorders of Cerebrospinal Fluid and Brain Extracellular Fluid

The chemical composition of the extracellular fluid (ECF) of the brain is similar to that of cerebrospinal fluid (CSF). Brain ECF is inaccessible for studies in humans, and serial determinations are difficult in animals. On the other hand, CSF can be sampled serially, in vivo, without altering physical or chemical parameters. Therefore, the CSF’s dynamic alterations are used to define dysfunction within the CSF compartment, as a direct index of dysfunction of brain ECF, and as an indirect index of cerebrocellular metabolism and dysfunction.
Taxonomic Uncertainty and Phylogenomics: Rescuing a Contentious Species Complex from the Anomaly Zone

Species are an indisputable unit for biodiversity conservation, yet their delimitation is fraught with both conceptual and methodological difficulties. A classic example is the taxonomic controversy surrounding the Gila robusta complex in the lower Colorado River of southwestern North America. Three species were originally defined according to subtle morphological differences with weak diagnostic power, with traditional genetic analyses failing to support the nominal species. Consequently, the complex was re-defined as a single polytypic unit, with the proposed 9threatened9 status of two putative species withdrawn at the federal level. Here, we utilized dense spatial and genomic sampling (N=387 and >22k loci) to re-evaluate the status of the complex, based on SNP-based coalescent and polymorphism-aware phylogenetic models. In doing so, all three species were supported as evolutionarily independent lineages, despite widespread phylogenetic discordance. To understand this discrepancy with past studies, we categorized evolutionary mechanisms driving discordance. We tested (and subsequently rejected) prior hypotheses suggesting that phylogenetic discord in the complex was hybridization-driven. Instead, we found the G. robusta complex to have diverged within the 9anomaly zone9 of tree space and, as such, have accumulated inconsistent patterns of diversity which have confounded prior studies. After extending these analyses with phylogeographic modeling, we propose that this is reflective of a rapid radiation promoted by Plio-Pleistocene tectonism. Our results not only support resurrection of the three species as distinct entities, but also offer an empirical example of how phylogenetic discordance can be categorized in other recalcitrant taxa.
Congenital Hypothyroidism: 8-Year Experience Using 2 Newborn Screens in Alabama.

Background/aims Newborn screening protocols for congenital hypothyroidism (CH) vary as to whether a TSH or T4 algorithm or some combination is performed. We aimed to determine the 3-year clinical outcome of infants diagnosed with CH and screen-positive for CH using a 2-screen protocol that measures both T4 and TSH on all specimens. Methods Retrospective analysis of patients with CH who were detected by first (NBS1) or second (NBS2) newborn screen in Alabama (2009-2016) and followed at our university-based practice. Clinical follow-up established the final diagnoses in 146 patients, including a subset of 72 patients with eutopic glands. Results 168 patients were studied: 139 (83%) were detected by NBS1 and 29 (17%) by NBS2. Screening T4 concentrations were 45% reduced in NBS2 compared to NBS1 (p= 0.0002). Thyroid dysgenesis was present in 55% of NBS1 patients while all in NBS2 were eutopic. Follow-up of 146 patients confirmed permanent CH in 92 patients in NBS1 (75%) and 5 in NBS2 (20%). Hispanic infants were only detected by NBS1, and 93% had permanent CH. Transient CH was associated with congenital heart disease. In patients with eutopic, permanent CH, dyshormonogenesis was confirmed in 23% of NBS1 patients and 40% of NBS2. One case of central CH was detected by each screen. Conclusions This 8-year, retrospective study buttresses the importance of a 2-screen approach for CH by identifying 5 infants with clinically significant permanent thyroid dysfunction including dyshormonogenesis and central hypothyroidism. It is the first 2-screen study to incorporate thyroid ultrasound. Disconcertingly, 4 of 5 second-screen infants with permanent CH had no risk factors for CH, and these infants would otherwise not have been detected.
Messages must be tuned to the target language: Some implications of crosslinguistic semantic diversity for neurolinguistic research on speech production

Abstract There are nearly 6,500 languages in the world, and they vary greatly with regard to both lexical and grammatical semantics. Hence, an early stage of utterance planning involves "thinking for speaking"—i.e., shaping the thoughts to be expressed so they fit the idiosyncratic meanings of the symbolic units that happen to be available in the target language. This paper has three main sections that cover three distinct types of crosslinguistic semantic diversity. Each type is initially elaborated with examples, and then its implications for the neurobiology of speech production are considered. Type 1: Semantic field partitions. These are exemplified by huge crosslinguistic differences in many domains of meaning, including colors, body parts, household containers, events of cutting and breaking, and topological spatial relations. When such differences are viewed from the perspective of contemporary neurocognitive theories which assume that most concrete concepts are subserved by both modal (i.e., sensory, motor, and affective) and transmodal (i.e., integrative) cortical systems, they imply that speakers must access language-specific semantic structures at multiple levels of representation in the brain. Type 2: Semantic conflation classes. Some languages have whole sets of words that systematically encode two or more components of meaning. For instance, in the roughly 53 Athabaskan languages there are no generic verbs like give, carry, or throw; instead, there are entire sets of 9–13 verbs for these kinds of actions, with each set making the same distinctions between the types of objects that are given, carried, or thrown, such as animate objects, round objects, stick-like objects, flat objects, etc. This regular conflation of [action + object] in Athabaskan verb meanings predicts that speakers frequently co-activate both action-related and object-related cortical regions in a functionally integrated fashion. Type 3: Grammatically obligatory semantic categories. This kind of crosslinguistic variation involves not only the particular dimensions of experience that speakers are forced to track for grammatical purposes, but also the precise contrasts that they must make along those dimensions, with examples including systems of nominal classification, tense, and evidentiality. It is still not known exactly where or how the meanings of grammatically necessary closed-class morphemes are implemented in the brain, but it is quite clear that whatever the neural substrates of these meanings turn out to be, they are strongly influenced by crosslinguistic differences. In all, by focusing on three separate forms of crosslinguistic semantic diversity, this paper reinforces Levelt's (1989) point that "messages must be tuned to the target language," and it also shows that this point continues to have significant consequences for neurolinguistic research on speech production.
Antarctic Sea Ice Variations 1973–1980

Analysis of Antarctic marine ice(1) showed a decrease of 2.5 million km2 in the total sea ice area between 1973 and 1980. While a decrease of 1.5 and 1.0 million km3 is found in the Pacific and Indian Ocean sectors, respectively, over this period, the sea ice area in the Atlantic sector hardly showed any trend at all. Non-seasonal variations of sea ice area in the ocean sectors, with trends removed, showed no significant correlations. Significant correlations exist between monthly total ice area and an index of the Southern Oscillation.
Breaking the exclusionary boundary between user experience and access

This paper expands the scope of designing for accessibility by proposing three design strategies that allow crosspollinations between accessible, user-centered design, cross-cultural design, and participatory design to break down the boundaries between the concepts of user experience and accessibility while involving all users in the UX research and design process.
Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy.

Objective To provide the first clinical report that 2 calcitonin gene-related peptide (CGRP) therapies, a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody, can be used concomitantly to treat refractory migraine. Methods Case reports are presented of 2 patients participating in a long-term safety study of rimegepant 75 mg oral tablets for acute treatment (NCT03266588). After Food and Drug Administration approval of erenumab, both patients started subcutaneous erenumab monthly as allowed per protocol. Results Patients were women 44 and 36 years of age with ≥2 decades of self-reported suboptimal response to multiple migraine medications. Patient 1 used rimegepant for 6 months and then started erenumab 70 mg subcutaneous monthly. Despite a response to preventive treatment with erenumab, she experienced substantial relief treating 7 of 7 acute attacks with rimegepant and eliminated regular, frequent use of ibuprofen and a caffeinated analgesic. Patient 2 used rimegepant for 60 days before starting erenumab 140 mg subcutaneously monthly. While on erenumab, 9 of 9 attacks treated with rimegepant responded. She stopped near-daily use of injectable ketorolac and diphenhydramine. While using rimegepant alone or together with erenumab, patients reported no related adverse events. Conclusions Rimegepant 75 mg may be effective for acute treatment during concomitant erenumab preventive administration. The mechanism underlying the benefits of concomitant use of a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody is unknown and requires further study. ClinicalTrials.gov identifier NCT03266588. Classification of evidence This study provides Class IV evidence that for patients with migraine using erenumab, rimegepant is effective for acute treatment.