cssi/SciSciGPT-SciSciNet huggingface dataset:
β-Adrenergic Receptor Signaling: An Acute Compensatory Adjustment—Inappropriate for the Chronic Stress of Heart Failure? Insights from Gsα Overexpression and Other Genetically Engineered Animal Models

Under normal physiological conditions, the heart must be able to increase its output 5-fold to supply the required blood flow to the coronary circulation and skeletal muscles during severe stress. This is normally met by ≈5-fold increases in myocardial contractility, ≈3-fold increases in heart rate, and additional increases in stroke volume.1 This increased load requires a commensurate increase in myocardial blood flow, because oxygen extraction across the heart is nearly complete, even under normal conditions. Accordingly, the design of the cardiovascular system evolved to conserve myocardial metabolic demand, and consequently coronary blood flow, at rest, but with considerable reserve that can be called on rapidly in times of stress. There is a host of compensatory adjustments, including changes in metabolic substrates and kinetics, as well as oxygen-carrying capacity, that may be recruited in response to stress. However, none is more important than the autonomic nervous system in general, and the sympathetic arm in particular, in terms of providing large, rapid changes in cardiac function. When this compensatory mechanism is unavailable, eg, after treatment with propranolol, the 3-fold increases in heart rate and 5-fold increases in myocardial contractility in response to exercise cannot be achieved.1 In this connection, it is recognized that heart failure is a state characterized by enhanced sympathetic tone, but when the failing myocardium is challenged by β-adrenergic stimulation in vivo or in vitro, the most frequent result is β-adrenergic downregulation or desensitization.2 3 4 5 An impairment of cardiac function leads to autocrine, paracrine, and neurohormonal adjustments, including a strong sympathetic component (Figure 1⇓); under acute conditions, these reflex adjustments are beneficial, as noted above. However, when the sympathetic nervous system is chronically and tonically stimulated, as occurs in the pathogenesis of heart failure, desensitization mechanisms are called into play, such that the …
A New Predictive Molecular Marker for Cetuximab Benefit in Rectal Cancer

Sclafani et al present data and suggest that tumor protein 53 (TP53) may be a predictive marker of cetuximab benefit in patients with rectal cancer undergoing neoadjuvant chemoradiation in this issue of the Journal (1). This article relies on an unplanned, retrospective analysis of molecular marker data on a subset of patients participating in the randomized phase II EXPERT-C clinical trial initially reported in 2012 (2). Patients with operable magnetic resonance imaging– defined high-risk rectal cancer received four cycles of capecitabine/ oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX-C). The primary endpoint was complete tumor response, which was modified during conduct of the study to include only the subset of patients whose tumors were KRAS/BRAF wild type. This was quite reasonably done when the impact of KRAS status on antitumor activity of epidermal growth factor receptor (EGFR)-inhibiting monoclonal antibodies was documented (3). However, the sample size of the study was not increased to assure the intended statistical power. One hundred and fifty eligible patients were randomly assigned. Based on a subset of patients with KRAS/BRAF wild-type tumors (46 patients who received cetuximab vs 44 patients who did not receive cetuximab as a component of treatment), the authors concluded that cetuximab led to a statistically significant increase in response rate and overall survival, but the primary end point of improved complete pathologic response was not met. Further follow-up revealed that contrary to the initial report, adding cetuximab was not associated with a statistically significant improvement in progression-free survival or overall survival in either KRAS/BRAF wild-type or unselected
The 3-D Deformation Behavior of a Lubricated Fiber Bundle

The purpose of this paper is to describe the response of an aligned, lubri cated fiber bundle to a general state of three-dimensional stress. Such an element can be used to represent an advanced composite during manufacturing. In general, this bundle can deform by both viscous shearing, and by "cylindrical" modes of elastic dilation. For a transversely isotropic bundle we show that there are five material functions needed to describe the constitutive behavior of the bundle, namely; 2 viscous functions, and 3 elastic functions. We first outline the viscous responses, and then derive functional relationships and compliances to describe the elastic behavior of the bundle. The application of this model to practical problems such as filament winding, prepregging, consolidation and fiber waviness are discussed.
Fuzzy semantics in collaborative processes

The paper reports on the reasoning of fuzzy semantics in collaborative processes, including groupware, workflow and CSCW software tools, as a fuzzy label relaxation process. A prototype Web based system is being implemented. In label relaxation, not only will new evidence update the fuzzy measures of a collection of propositions, but also the constraint satisfaction among those propositions in distributed cognitive maps will revise the measures. This mechanism is somewhat similar to human group behavior, which is an evolutive process converging to the most satisfactory result.
Consumerization in the IT Service Ecosystem

Most of the available literature on IT consumerization focuses on current practices--from operational aspects of BYOD to its disruptive effects--but does little to illuminate the dynamics behind the trend's emergence. Exploring the driving forces behind consumerization is essential if IT organizations are to both make sense of the current dynamics of transformation and disruption and formulate effective strategies in response. This article is one of the first attempts to explain these dynamics as part of a logical progression, from the Web's invention in 1989 to its evolution into machine-to-machine communication through Web services to SOA's role as an application discipline in virtualized cloud infrastructure context--all of which brings us to today's BYOD and BYOA.
Trade Performance and Labor Standards: A Dynamic Panel Data Approach

What is the effect of more stringent labor standards on trade performance? Several recent papers have attempted to identify the partial effects of international labor standards on trade by using ILO labor standards ratifications as instruments in cross-sectional regressions. This paper contributes to the literature by using more direct measures of labor standards in a dynamic panel data model framework. The model covers up to 112 countries over the period 1980-2004, and it is robust to unobserved heterogeneity among countries as well as endogeneity among explanatory variables. The new measures of international labor standards used in the estimation correct for endogeneity and potential biases. In addition, I complement the analysis by including the quality of domestic institutions in influencing trade performance. The results suggest that better labor standards do not deteriorate the trade performance of a country, and that better institutions promote trade performance.
Targeted molecular imaging of prostate cancer using tumor endothelium homing Arg-Arg-Leu peptides

14582 Background: Tumor endothelial cells express a specific and unique cell surface signature. We have previously reported on the discovery of tumor endothelial cell (TDEC) binding peptides that p...
Preventing Overdiagnosis and Overtreatment: Just the Next Step in the Evolution of Breast Cancer Care

The problem of overdiagnosis and overtreatment has been highlighted in breast cancer and many other cancer types, most notably prostate cancer. Addressing this problem presents an opportunity to continue the evolution of breast cancer care. Advances in technology, such as molecular subtyping, have increased the understanding of breast cancer biology and the range of associated behavior, and have provided tools that allow greater personalization of treatment. This article identifies 3 areas of breast cancer care where opportunity currently exists to refine management strategies and help decrease overtreatment and overdiagnosis: the use of adjuvant-external beam radiation in invasive breast cancer, the application of aggressive treatment for all ductal carcinoma in situ, and the authors' approach to breast cancer screening. Personalizing treatment based on patient and tumor characteristics holds promise for minimizing harms and maximizing benefits. This approach will allow continual improvement and ultimately result in providing the right treatment for each patient.
Numerical Simulation of Global-Scale Atmospheric Chemical Transport with High-Order Wavelet-Based Adaptive Mesh Refinement Algorithm

AbstractHigh computational cost associated with numerical modeling of multiscale global atmospheric chemical transport (ACT) imposes severe limitations on the spatial resolution of fixed nonadaptive grids. Recently it has been shown that the interaction of numerical diffusion caused by the crude resolution with complex velocity field of atmospheric flows leads to large numerical errors. To address the described difficulties, the authors have developed a wavelet-based adaptive mesh refinement (WAMR) method for numerical simulation of two-dimensional multiscale ACT problems. The WAMR is an adaptive method that minimizes the number of grid points by introducing a fine grid only in the locations where fine spatial scales occur and uses high-order spatial discretization throughout the computational domain. The algorithm has been tested for several challenging ACT problems. Particularly, it is shown that the method correctly simulates dynamics of a pollution plume traveling on a global scale, producing less tha...
Mouse Models of Human Retinal Disease Caused by Expression of Mutant Rhodopsin

The genetic basis for a wide range of inherited retinal diseases has been identified in recent years. To date, over 118 retinal disease loci have been mapped, for which 55 genes have been isolated (Clarke et al. 2000). Of these diseases, inherited photoreceptor degenerations represent a significant proportion of diseases that cause serious visual impairments in individuals of all ages and ethnic backgrounds (Berson 1996). While most forms of photoreceptor degeneration are characterized by rod and/or cone dysfunction, individual subtypes are further classified based on the type of inheritance, pattern of visual loss, appearance of the retina, and the gene defect causing these symptoms (Dryja et al. 1990b; Berson 1996; Wang et al. 2001). One of the most prominent genes that has been shown to cause progressive photoreceptor degeneration when mutated, is the rhodopsin gene. Patients carrying a number of different mutations in rhodopsin have displayed clinical symptoms of retinitis pigmentosa, varying in the severity of visual impairment (Dryja et al. 1990a; Dryja et al. 1990b; Dryja et al. 1991).
Event-based electric vehicle scheduling considering random user behaviors

Uncontrolled Electric Vehicle (EV) and Plug-in Hybrid Electric Vehicle (PHEV) charging within a local distribution grid may cause unexpected high load, which further results in power quality degradation. However, coordinating charging behaviors of a number of EVs is a challenging task, which involves not only the deterministic schedule computing but also nondeterministic EV driver behaviors with random arrival time and energy demands. Previous researches in this area rarely consider these random behaviors for real EV users. In this paper, an implementable event-based cost optimal scheduling algorithm (ECSA) is developed, which solves EV scheduling problem by dynamically estimating the stay duration and energy demand for each participating EV user. Datasets, including users' historical charging records and time series meter data collected from Electric Vehicle Supply Equipments (EVSEs) in UCLA campus, are utilized for feature extraction. Based on that, proper inference technique is employed to determine parameters within each charging session. In addition, solar generation integration into EVSEs is also considered in our problem formulation. The proposed approaches are tested and validated by real EV charging schedules of users in UCLA campus. The results from simulation experiment demonstrate that the proposed algorithm has a better performance in cost minimization and load shifting compared to existing equal-sharing scheduling algorithm (ESSA).
Kinetic Enhancements in DNA–Enzyme Nanostructures Mimic the Sabatier Principle

Advances in DNA bionanotechnology have led to the ability to create structures with well-defined chemical and physical features at the nanoscale. Such nanostructures can be used to create spatially organized enzymatic cascades that promote substrate channeling and result in enhanced cascade kinetics. Here, we investigate the effects of substrate–scaffold interactions on the catalytic activity of an enzyme–DNA complex using horseradish peroxidase (HRP) and a nanoscale DNA scaffold with three addressable sites. Kinetic assays with a library of HRP substrates revealed that DNA scaffolding enhances HRP activity in a manner that is analogous to the Sabatier Principle. In this case, the binding of the substrate is to the scaffold and not to the catalyst, but the Sabatier trend holds: weak and strong binding substrates showed no enhancement in kinetics, whereas intermediately bound substrates result in >300% increase in enzyme activity.
Sensitivity of females of the C stock to male infection with the mammary tumor agent.

SummaryFemales of the agent-free, but susceptible. C (Bagg albino) stock remained free of mammary cancer after they were bred with males of the C strain and with males of another stock lacking the mammary tumor agent (MTA). However, when they were mated with males of high cancerous strains, differences were noted in the ability of the males of these strains to transfer the agent and infect the C females. After C females were mated with males of the cancerous Z(C3H) strain, over 50% of the females developed mammary cancer, and the same incidence was observed in females with amputated uterine horns as in intact litter-mate controls. The source of the agent may be of some significance in male transmission experiments. In some crosses, only preliminary data could be reported in the hybrids.
Segmenting Audiences and Tailoring Messages: Using the Extended Parallel Process Model and Cluster Analysis to Improve Health Campaigns

Half of all pregnancies in young adult women are unintended, but few interventions have been successful in encouraging contraceptive use. The group heterogeneity likely contributes to the lack of success. Segmenting based on theories that provide meaningful information may improve tailoring and targeting of behavioral interventions. Previous research has indicated that threat, efficacy, and fear were important factors in influencing intentions to use contraceptives; therefore, the extended parallel process model (EPPM) was used for this cluster analysis. A telephone survey of randomly selected 18- to 30-year-old women in Iowa was conducted (N = 401). The constructs of EPPM and age were used for conducting a K means cluster analysis with four clusters. The cluster analysis pointed to the importance of fear, perceived susceptibility, and age. All of the clusters had varying degrees of ambivalence about the severity of a pregnancy. Cluster 1 (27.8%) had high susceptibility, with little fear. Cluster 2 (23.8%...
The guilty pleasures of bigotry: ethnic stereotypes in Trevor Nunn's Merchant of Venice and Dave Chappelle's pixie sketches

ABSTRACTTrevor Nunn's 1999 Royal National Theatre production of The Merchant of Venice and Dave Chappelle's “pixie sketches”, produced in 2005 for Comedy Central USA, addressed the same challenge: how does one present ethnic stereotypes in a way that undermines those stereotypes rather than reinforcing them? The different representational strategies adopted by Nunn and Chappelle illustrate the different conventions that govern the representation of ethnicity in high and popular culture. Nunn downplayed the most stereotypical elements of Merchant and guided viewers towards a clear and obvious moral choice. He updated the setting of the play to Weimar Germany, evoking a strong sense of specific social context and prompting the audience to identify with Shylock as the victim of a toxic culture. Chappelle presented a series of hyperbolic racist caricatures that tempted his audience to make the wrong choice. The pixie sketches both solicit and chastise laughter, potentially making viewers aware of their moment...
Effect evaluation of occupational hazards in medical X-ray diagnosis construction project of a hospital

[Objective]To evaluate the occupational hazards control effect of a hospital construction project on radiation protection,and to put forward advices for the hospital and a approval basis for the health administration.[Methods]adopt the methods of occupation hygiene field survey and spot test to synthetic analyze the factor on occupational hazards.[Methods]Occupational hygiene surveys and on-site detection were adopted to comprehensively analyze the occupational hazards.[Results]The radiologic design and protection measures were scientific and rational.The surrounding radiation level was qualified.Personal dose monitoring had not been carried out in 2012.The occupational health status of 4 radiation workers were accorded with the standards,one worker's WBC count of peripheral blood was lower than 4.0×109/L.[Conclusion]The construction project is feasible,can be formally put into operation.It is suggested to improve the hospital radiation protection management system and the personal protection equipment for client,and to further improve the occupational health examination and personal dose monitoring of radiation workers.
Distance Domains, Skeletal Structures, and Representative Ranks

Prioritization can proceed through partnership between procedures and perception. Perception is promoted by pictorial portrayal on a page, which is most manageable in two dimensions. Therefore, we consider capturing contrasts among contingents compactly in couplets of coordinates on synthetic scales (Zuur et al. 2007). What we call “distance domains” derived through multidimensional scaling are appropriate for this (Borg and Groenen 2005; Cox and Cox 2001; Green et al. 1989).
Literary and Religious Activity

The second pre-Christian millennium was one of cultural pluralism in the Near East, with Canaan, Egypt and Mesopotamia interacting, exchanging their intellectual products and, with the Canaanites, serving as the intermediary. But not much of the Canaanite literature has survived. The ordinary writing material was perishable papyrus, and the written material related mostly to business transactions. Ironically they who perfected and disseminated the earliest, most durable and most adequate system of writing, the alphabet, left so little by way of written records.
THE EXPERIMENTS OF CLAUSER AND OF HOLT

This chapter describes the experiments of Kocher and Commins. Mere improvement of the Kocher–Commins experiment is not sufficient for a reliable experimental decision whether for two-photon polarization correlations the quantum-theoretical prediction or whether some hidden-variables prediction is the correct one. The fact that the rules of quantum theory for calculating probabilities from squares of coefficients may not be valid in hidden-variables theories of the second kind is readily admitted. According to hidden-variables theory, the rules of quantum theory hold only as a crude first approximation for systems of atomic size, and need not hold when applied to coincidences behind filters separated by macroscopic distances. Moreover, these rules are valid only statistically. As far as quantum theory has validity, then, one might expect that angular momentum would be conserved on the average. Individual photons, however, would be steered by hidden variables. A characteristic of any hidden-variables theory of the second kind is that supposedly the values of the hidden variables tell us for each of the two photons separately what will happen to it when it meets a polarization filter in a particular orientation.
Myth, the New “M” Theory of Education Offering Eleven Universes

In this last chapter my intention is to bring together voices that are not commonly joined: poets, psychoanalysts, and writers; together with curriculum theorists; together with students in my myth classes as well as in my Absurdist Imagination class; along with my own riffs. There are four types of voices in each section (universe), no one voice speaking to another with any intention to contradict; rather, the voices sing their own tunes. Together what we have is an orchestration under my selection that suggests to me the kind of sweet dissonance and rhythm found in jazz.
Correlation of link outages in low-mobility spatial wireless networks

In this paper we consider a network where the nodes locations are modeled by a realization of a Poisson point process and remains fixed or changes very slowly over time. Most of the literature focuses on the spatial average of the link outage probabilities. But each link in the network has an associated link-outage probability that depends on the fading, path loss, and the relative locations of the interfering nodes. Since the node locations are random, the outage probability of each link is a random variable and in this paper we obtain its distribution, instead of just the spatial average. This work supplements the existing results which focus mainly on the average outage probability averaged over space. We propose a new notion of transmission capacity (TC) based on the outage distribution, and provide asymptotically tight bounds for the TC.
Association between lateral patellar osteoarthrosis and knee morphology and alignment in young adults.

Aim To assess whether patellar and trochlea morphology and patellar alignment are associated with lateral patellar osteoarthrosis/chondrosis (OAC) in young adults. Materials and methods Magnetic resonance imaging (MRI) images of 183 subjects (81 cases, 102 controls) aged 21–35 years of age were evaluated. Quantitative measurements of patella and trochlea morphology and patellar alignment were obtained. Axial and sagittal MRI images were reviewed to grade the severity of focal cartilage defects along the lateral facet of the patella. Controls had knees without any abnormalities and were compared to cases with mild and severe lateral patellar OAC. Multivariable logistic regression was used to assess associations between measurements and lateral patellar OAC adjusting for body mass index. Results Cases were more likely to have higher Insall–Salvati ratios (OR=350; p −3 ; p p =0.009), decreased trochlear cartilage overlap with the patellar cartilage (OR=0.086; p =0.023), and a less angulated lateral patellofemoral angle (OR=0.903; p =0.028), compared to controls. Cases were also more likely to have patellar tendinosis (OR=5.265; p =0.045) and oedema in the superolateral aspect of Hoffa's fat pad (OR=9.872; p Conclusion Patellar and trochlear morphology and patellar alignment are associated with lateral patellofemoral compartment OAC in young adults.
Substantive Equality and Sexual Orientation: Twenty Years of Gay and Lesbian Rights Adjudication Under the South African Constitution

One of the exceptional elements of the South African Equality Clause is its novel and progressive inclusion of anti-discrimination protections for lesbians and gay men. The prohibition of discrimination based on sexual orientation is particularly important because it occurred — for the first time in any national constitution — as a result of the closely watched drafting of South Africa’s historic “human rights” Constitution. The South African Constitution advanced the hopes of international gay rights advocates and set a benchmark for future constitutional drafters. Over the last two decades, the Constitutional Court of South Africa decriminalized same-sex sexual activity, required equal treatment of same-sex life partners in areas of immigration and government benefits, and affirmed the fundamental validity of same-sex relationships, including recognition of full marriage equality. The Court’s opinions included express affirmations of the dignity and equality of gays and lesbians in an unbroken series of unanimous, pro-gay decisions. But although twenty years have passed since sexual orientation discrimination was prohibited by the Equality Clause, its practical effect has been markedly inadequate to achieve the safety and social equality of LGBT persons in South Africa. In sharp contrast to its expansive textual protections and progressive jurisprudence, the lived reality of South African gays and lesbians, particularly in poorer communities, is typified by condemnation, discrimination, and homophobic violence. Hence, the Equality Clause is a symbol of both the progressive aims of the post-apartheid Constitution and the appalling gulf between those aims and reality. Examining the historical successes and failures of the Constitution’s sexual orientation protections highlights three categories of insights drawn from the last two decades of constitutional rights in South Africa. These lessons include an encouraging insight about novel and progressive elements in the drafting of modern constitutions; some modest claims about the capacity of courts to combat inequality based on sexual orientation despite the limitations of purely legal victories; and a hopeful affirmation of the value of even unrealized constitutional aspirations for the fields of comparative constitutionalism and gay and lesbian equality.
Characterization of GPGPU workloads on a multidimensional heterogeneous processor

Systems with multiple forms of heterogeneity, including functional, performance, and dynamic heterogeneity, are now commercially available. The use and tuning of any of these options can impact other options and so it is important to understand their interactions. This work characterizes the power and performance implications of multiple dimensions of heterogeneity from a commercial multidimensional heterogeneous processor on commonly evaluated GPGPU workloads.
Comparison of Phonon Damping Behavior in Quantum Dots Capped with Organic and Inorganic Ligands.

Surface ligand modification of colloidal semiconductor nanocrystals has been widely used as a means of controlling photoexcited-state generation, relaxation, and coupling to the environment. While progress has been made in understanding how surface ligand modification affects the behavior of electronic states, less is known about the influence of surface ligand modification on phonon behavior, which impacts relaxation dynamics and transport phenomena. In this work, we compare the dynamics of optical and acoustic phonons in CdTe quantum dots (QDs), CdTe/CdSe core/shell QDs capped with octadecylphosphonic acid ligands, and CdTe QDs capped with Se2– to ascertain how ligand exchange from native aliphatic ligands to single-atom Se2– ligands affects phonon behavior. We use transient absorption spectroscopy and observe modulations in the kinetics of excited-state decay due to QD lattice vibrations from both optical and acoustic phonons, which we describe using the damped oscillator model. The longitudinal optica...
Personality and Values at Work

Individuals' personality and values have important implications in the workplace and can be used in conjunction with other metrics to predict outcomes relevant to organizations, such as job performance. Instruments for assessing personality and values can thus be potent tools in hiring and promotion processes. In this article, we review the history of research surrounding personality and values in the workplace, discuss recent contributions to the literature, and identify existing issues and areas of future research.
Dietary fiber constituents of selected fruits and vegetables

This study compared the dietary fiber (DF), neutral detergent fiber (NDF), cellulose, hemicellulose, lignin, and pectin content of selected fruits and vegetables. Apples and peaches (fresh and canned), oranges (fresh), strawberries (fresh, canned, and frozen), carrots, green beans, and potatoes (fresh, fresh cooked, canned, and frozen), and tomatoes (fresh, fresh cooked, and canned) were studied. When possible, two varieties, two stores, and name and store brands were chosen. Samples were analyzed for NDF, acid detergent fiber, 72% sulfuric acid, lignin, and pectin. From those values, DF, cellulose, and hemicellulose were calculated. Fresh fruits in gm/100gm wet weight had decreasing DF, NDF, and hemicellulose values as follows: apples, peaches, strawberries, and oranges. Apples were highest in cellulose; strawberries, highest in lignin; and oranges, highest in pectin. Fresh-cooked vegetables in gm/100gm wet weight have decreasing DF and NDF values as follows: green beans, carrots, potatoes, and tomatoes. Green beans were highest in cellulose and hemicellulose; potatoes highest in lignin; and carrots highest in pectin. On a wet-weight basis, fresh applesand peaches, fresh-cooked green beans, canned carrots, and canned and frozen potatoes were higher in DF and NDF than other forms of the fruit or vegetable. There were few differences according to stores, brands, or varieties of fruits and vegetables. On a dry-weight basis, fresh apples, peaches, strawberries, green beans, and tomatoes appear to have higher DF and NDF contents than their processed counterparts. Fresh-cooked carrots and fresh potatoes appear to have less DF and NDF than their canned and frozen counterparts.
Real-Time Magnetic Length-Based Vehicle Classification: Case Study for Inductive Loops and Wireless Magnetometer Sensors in Oklahoma State:

Providing reliable, real-time vehicle volume and classification information is vital for 21st century intelligent transportation systems (ITS). Large vehicles have a major impact on traffic flow, a...
Ultrasonic Evaluation of Segmental Variability in Additively Manufactured Metal Components

One of the primary challenges with additively manufactured metal components is the potential for the material heterogeneity, such as the variations in density, porosity, and elasticity. These heterogeneities are difficult to predict and can cause the deviation in material strength and structural reliability from the specified design. This paper presents a novel approach to the ultrasound characterization of spatially varying material properties and its application to a sample manufactured by the selective laser melting. The method is demonstrated for a 3D-printed aluminum alloy sample. The independent measurements of the elastic modulus, the surface morphology, and the X-ray computed tomography of the sample were consistent with the ultrasound results.
Abstract 2076: Targeting vulnerable aberrant cancer-associated pathways by rationalized triple combination regimens to effectively control urothelial carcinoma cells in vitro and in vivo

Urinary bladder cancer (UBC) is the fifth-most common cancer in the United States, and urothelial carcinomas (UCs) account for more than 90% of UBCs. Although current therapies are effective in the short-term treatment of UCs, the high tendency (>50%) for them to recur and progress to life threatening, advanced muscle-invasive UCs requires life-long surveillance with extended medical care. Thus, it still requires extensive therapeutic development to achieve an effective control of UC recurrence and improve the response rate and overall survival for UC patients. To develop effective and safe regimens to control the development and recurrence of advanced UCs, we investigated the efficacy of rationalized combination regimens in controlling UC cells in vitro and UC cell-derived xenografts (CDXs) in vivo. Our in vitro studies identified a triple combination of gemcitabine, romidepsin, and cisplatin, which are all FDA-approved anticancer agents, effective in synergistically inducing death and reducing drug resistance of various UC cell lines. Our studies also revealed that UC-associated aberrant pathways, including mitochondrial reactive oxygen species (ROS) and the ERK-Nox pathway, which were already induced in UC cells, were enhanced by the triple combination regimen to play essential roles for inducing apoptosis and reducing resistance. We also detected that the unfolded protein response played a role in modulating cell death induced by the regimen. Our in vivo studies used a tolerable protocol for administering combination regimens into animals. Our studies verified the efficacy of the triple combination gemcitabine plus romidepsin and cisplatin regimen, versus double combination regimens, in controlling UC CDXs in immune-deficient mice. In conclusion, our studies indicated that a rationalized triple combination of gemcitabine plus romidepsin and cisplatin regimen was more effective than double combination regimens in modulating UC-associated vulnerable aberrant pathways and controlling UC tumor development and recurrence in animals with low tolerable/ reversible adverse effects. Thus, the triple combination gemcitabine plus romidepsin and cisplatin regimen should be promptly considered as an advanced treatment over the conventional double combination gemcitabine plus cisplatin regimen in clinical trials in order to control advanced UCs. Citation Format: Hwa-Chain R. Wang, Pawat Pattarawat, Jinquan Wang, Robert Donnell. Targeting vulnerable aberrant cancer-associated pathways by rationalized triple combination regimens to effectively control urothelial carcinoma cells in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2076.
A prospective longitudinal relation between elevated use of electronic devices and use of electronic nicotine delivery systems.

Abstract Background In recent years, there has been a rapid increase in the use of both electronic nicotine delivery systems (ENDS) and electronic devices among U.S. youth. Informed by the Diffusion of Innovations Theory (DIT), it was hypothesized that elevated use of electronic devices (EUED) prospectively would predict ENDS use among youth. Methods Data were drawn from the Population Assessment of Tobacco and Health (PATH) Study, a longitudinal cohort study in a nationally representative sample. Participants who were 12–17 years old, and naive to both conventional cigarettes and ENDS at baseline (N = 11,325) were sampled. A total of 8723 respondents had matched data from Wave 1 to Wave 2 and 6051 respondents had matched data for all the three waves. Multivariable sequential logistic regressions were conducted to examine determinants of ENDS use in later waves using R version 3.5.2. Results Among youth who were naive to both ENDS and conventional cigarettes at baseline, those with EUED were more likely to initiate ENDS use in later years than those without EUED even after controlling for exposure to ENDS advertisements and other well-established covariates of ENDS use. Daily (adjusted odds ratio [AOR] ranges from 2.76 to 3.56) and weekly (AOR ranges from 2.16 to 2.65) social networking service (SNS) users were more likely to initiate ENDS use than non-users of SNS in the adjusted models. Conclusions The findings support the hypothesis that EUED prospectively predicts ENDS use among youth. The use of DIT framework helps understand the link between EUED and ENDS use.
Murine coronavirus infection activates the aryl hydrocarbon receptor in an indoleamine 2,3-dioxygenase-independent manner, contributing to cytokine modulation and proviral TCDD-inducible-PARP expression

The aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor/transcription factor that modulates several cellular and immunological processes following activation by pathogen-associated stimuli, though its role during virus infection is largely unknown. Here, we show that AhR is activated in cells infected with mouse hepatitis virus (MHV), a coronavirus (CoV), and contributes to the upregulation of downstream effector TCDD-inducible poly(ADP-ribose) polymerase (TiPARP) during infection. Knockdown of TiPARP reduced viral replication and increased interferon expression, suggesting that TiPARP functions in a proviral manner during MHV infection. We also show that MHV replication induced the expression of other genes known to be downstream of AhR in macrophages and dendritic cells and in livers of infected mice. Further, we found that chemically inhibiting or activating AhR reciprocally modulated the expression levels of cytokines induced by infection, specifically, interleukin 1β (IL-1β), IL-10, and tumor necrosis factor alpha (TNF-α), consistent with a role for AhR activation in the host response to MHV infection. Furthermore, while indoleamine 2,3-dioxygenase (IDO1) drives AhR activation in other settings, MHV infection induced equal expression of downstream genes in wild-type (WT) and IDO1-/- macrophages, suggesting an alternative pathway of AhR activation. In summary, we show that coronaviruses elicit AhR activation by an IDO1-independent pathway, contributing to upregulation of downstream effectors, including the proviral factor TiPARP, and to modulation of cytokine gene expression, and we identify a previously unappreciated role for AhR signaling in CoV pathogenesis.IMPORTANCE Coronaviruses are a family of positive-sense RNA viruses with human and agricultural significance. Characterizing the mechanisms by which coronavirus infection dictates pathogenesis or counters the host immune response would provide targets for the development of therapeutics. Here, we show that the aryl hydrocarbon receptor (AhR) is activated in cells infected with a prototypic coronavirus, mouse hepatitis virus (MHV), resulting in the expression of several effector genes. AhR is important for modulation of the host immune response to MHV and plays a role in the expression of TiPARP, which we show is required for maximal viral replication. Taken together, our findings highlight a previously unidentified role for AhR in regulating coronavirus replication and the immune response to the virus.
Long-term Results From the FRESH RCT: Sustained Reduction of Children's Tobacco Smoke Exposure

Introduction Standard care interventions to reduce children's tobacco smoke exposure (TSE) may not be sufficient to promote behavior change in underserved populations. A previous study demonstrated the short-term efficacy of an experimental counseling intervention, Family Rules for Establishing Smokefree Homes (FRESH) compared with standard care on boosting low-income children's TSE reduction and maternal smoking at 16-week end of treatment (EOT). This study tested long-term posttreatment efficacy of this treatment through a 12-month follow-up. Study design This study was a two-arm RCT. Setting/participants Maternal smokers (n=300) not seeking cessation treatment were recruited from low-income, urban communities. Participants exposed their Intervention The FRESH behavioral intervention included 2 home visits and 7 phone sessions. FRESH used cognitive behavioral skills training, support, problem-solving, and positive social reinforcement to facilitate the adoption of increasingly challenging TSE-protection behaviors. No nicotine-replacement therapy or medication was provided. Main outcome measures Primary outcomes were child cotinine (TSE biomarker) and reported TSE from EOT through 12 months after treatment. A secondary outcome was bioverified maternal smoking cessation. Results Compared with controls, children in FRESH had significantly lower cotinine (β= −0.31, p Conclusions Study results with a sample of underserved maternal smokers demonstrated that the short-term effect of FRESH counseling at 16-week EOT was maintained through 12 months after treatment—for both bioverified child TSE reduction and maternal smoking cessation. Smokers in low-income communities demonstrate elevated challenges to success in standard smoking treatment. FRESH follow-up results suggest the high potential value of more-intensive behavioral intervention for vulnerable smokers. Trial registration This study is registered at www.clinicaltrials.gov NCT02117947.
Clearing the cobwebs: An analysis of the timing of youth concussion legislation in U.S. states.

Abstract After decades of ignoring head injury in youth sports, U.S. states passed youth concussion legislation with stipulations about when athletes can return to play. Why were some states slower to pass laws than others? We consider this question through the lens of institutional medicalization, where medically informed policies are enacted. Our study recognizes the uneven nature of policy enactment across time and space with event history methods. We explore the influence of high school sport participation and other variables on the timing of legislation in all fifty states, 2007–2014. States with more high school football participation, as well as states with a strong college football presence, passed concussion laws later. Conversely, states with stronger orientations toward gender egalitarianism adopted laws sooner. These factors reflect sources of receptivity and resistance that underlie the process of institutional medicalization. Our approach offers one of the few quantitative studies of institutional medicalization and provides a template for future quantitative research in this area.
The Kähler geometry of certain optimal transport problems

Let X and Y be domains of ℝn equipped with probability measures μ and ν, respectively. We consider the problem of optimal transport from μ to ν with respect to a cost function c:X×Y→ℝ. To ensure that the solution to this problem is smooth, it is necessary to make several assumptions about the structure of the domains and the cost function. In particular, Ma, Trudinger, and Wang established regularity estimates when the domains are strongly relativelyc-convex with respect to each other and the cost function has nonnegative MTW tensor. For cost functions of the form c(x,y)=Ψ(x−y) for some convex function Ψ:ℳ→ℝ, we find an associated Kahler manifold on Tℳ whose orthogonal antibisectional curvature is proportional to the MTW tensor. We also show that relative c-convexity geometrically corresponds to geodesic convexity with respect to a dual affine connection on ℳ. Taken together, these results provide a geometric framework for optimal transport which is complementary to the pseudo-Riemannian theory of Kim and McCann (J.Eur. Math. Soc. 12:4 (2010), 1009–1040).We provide several applications of this work. In particular, we find a complete Kahler surface with nonnegative orthogonal antibisectional curvature that is not a Hermitian symmetric space or biholomorphic to ℂ2. We also address a question in mathematical finance raised by Pal and Wong (2018, arXiv:1807.05649) on the regularity of pseudoarbitrages, or investment strategies which outperform the market.
Demonstration of Selective Single-Barium Ion Detection with Dry Diazacrown Ether Naphthalimide Turn-on Chemosensors.

Single-molecule fluorescence imaging (SMFI) of gas-phase ions has been proposed for “barium tagging,” a burgeoning area of research in particle physics to detect individual barium daughter ions. Th...
Path to Automating Ocean Health Monitoring.

Marine ecosystems directly and indirectly impact human health, providing benefits such as essential food sources, coastal protection and biomedical compounds. Monitoring changes in marine species is important because impacts such as overfishing, ocean acidification and hypoxic zones can negatively affect both human and ocean health. The US west coast supports a diverse assemblage of deep-sea corals that provide habitats for fish and numerous other invertebrates. Currently, National Oceanic Atmospheric Administration (NOAA) scientists manually track the health of coral species using extractive methods. In this paper, we test the viability of using a machine learning algorithm Convolutional Neural Network (CNN) to automatically classify coral species, using field-collected coral images in collaboration with NOAA. We fine tune the hyperparameters of our model to surpass the human F-score. We also highlight a scalable opportunity to monitor ocean health automatically while preserving corals.
IoT Attacks and Malware

The huge number of deployed Internet of Things (IoT) devices combined with the evolution of multiple technologies like machine learning, embedded systems, and cloud- and edge-based services has resulted in complex dynamic IoT networks. IoT networks are however increasingly a target for attacks and breaches. Recent progresses in artificial intelligence can result in effective security solutions. In order to design such AI-based solutions, an analysis of the structure and kill chain of IoT attacks is required. However, the IoT network attack surface is complex and heterogeneous because of devices that are different with respect to functions, protocols, architectures, and manufacturers and operate with deeply intertwined physical and software components. As a result, the structure of an attack in IoT networks is different from attacks in traditional network settings, and therefore conventional kill chains cannot be directly used to classify attacks. In this chapter, we survey different types of IoT attacks and malware observed in recent times. We then propose a new classification structured specifically for IoT attacks and malware with respect to which AI-based effective security solutions can be designed.
Anti-capitalism and the Near Future: In Mohsin Hamid’s Exit West and Louise Erdrich’s The Future Home of the Living God

This chapter argues that literary texts that imagine anti- or post-capitalist spaces are important for preparing readers to enter them and to make them possible. Mohsin Hamid’s Exit West and Louise Erdrich’s The Future Home of the Living God explore the sociopolitical significance of the anti-capitalist futures they manifest. Hamid imagines a possible “desirable future,” subverts capitalist myths of inevitability, and implicitly relegates the current apocalyptic narrative trend to a failure of imagination, while Erdrich’s novel takes the shape of a meta-text bent on imagining an alternative future to the future the novel posits. Hamid and Erdrich register the savagery of late capitalism and at the same time extend radical hope in their characters’ forging of interdependence in the place of individualism and their respective worlds’ rewarding of communitarian rather than capitalist values.
Prejunctional α2-adrenoceptors and peroxide-induced potentiation of norepinephrine release from the bovine iris

Peroxides can enhance field-stimulated [3H]norepinephrine ([3H]NE) release in isolated irides from several mammalian species. In the present study, we investigated the role of prejunctional α2-adrenoceptors in peroxide-induced potentiation of sympathetic neurotransmission in bovine isolated irides. Isolated hemi-irides were incubated in a Krebs buffered-solution containing [3H]NE and prepared for studies of neurotransmitter release using the superfusion method. α2-Adrenoceptor agonists, oxymetazoline, UK-14304 and clonidine inhibited field-stimulated [3H]NE overflow without affecting basal tritium efflux. Pretreatment of tissues with H2O2 (300 μM) had no effect on inhibition of evoked [3H]NE release caused by the α2-adrenergic agonists. However, H2O2 (300 μM) caused significant (P < 0.01) leftward shifts of excitatory concentration-response curves to yohimbine (10 nM–1 μM). In contrast, yohimbine (1 μM) did not prevent the enhancement of evoked [3H]NE overflow induced by H2O2 (300 μM). In conclusion, excitatory effects of peroxides on sympathetic neurotransmission in bovine irides are not mediated by prejunctional α2-adrenoceptors.