cssi/SciSciGPT-SciSciNet huggingface dataset:
ASHMI Induced Long-lasting Tolerance to Allergen Exposure In An Asthma Model Is Interferon -γ, But Not TGF-β Dependent

Chronic allergic asthma is the result of a Th2biased immune status. Current asthma therapies control symptoms in some patients, but a long lasting therapy has not been established. ASHMITM, a Chinese herbal formula improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma. We evaluated the persistence of ASHMITM beneficial effects following therapy in a murine model of persistent asthma and the immunological mechanisms underlying such effects. BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyperreactivity (AHR) and inflammation (OVA mice). Additional OVA mice were treated with ASHMITM (OVA/ASHMITM) or water (OVA/Sham) for 4 weeks, and then challenged immediately and eight weeks post-therapy. In other experiments OVA mice received ASHMITM treatment with concomitant neutralization of IFN-γ or TGF-β. Effects on airway responses, cytokine and OVA-specific IgE levels were determined 8 weeks post-therapy. Prior to treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMITM and did not re-occur following OVA re-challenge up to 8 wks post-therapy. Reduced allergen-specific IgE and Th2 cytokine levels, and increased IFN-γ levels also persisted at least 8 wks post-therapy. ASHMITM effects were eliminated by neutralization of IFN-γ, but not TGF-β, during therapy. Conclusion—ASHMITM induced long-lasting post-therapy tolerance to antigen-induced inflammation and AHR. IFN-γ is a critical factor in ASHMITM effects.
Survival and Breeding Transitions for a Reintroduced Bison Population: a Multistate Approach

The iconic plains bison (Bison bison) have been reintroduced to many places in their former range, but there are few scientific data evaluating the success of these reintroductions or guiding the continued management of these populations. Relying on mark-recapture data, we used a multistate model to estimate bison survival and breeding transition probabilities while controlling for the recapture process. We tested hypotheses in these demographic parameters associated with age, sex, reproductive state, and environmental variables. We also estimated biological process variation in survival and breeding transition probabilities by factoring out sampling variation. The recapture rate of females and calves was high (0.78 6 0.15 (SE)) and much lower for males (0.41 6 0.23), especially older males (0.17 6 0.15). We found that overall bison survival was high (.0.8) and that males (0.80 6 0.13) survived at lower rates than females (0.94 6 0.04), but as females aged survival declined (0.89 6 0.05 for F L 15 yr old). Lactating and non-lactating females survived at similar rates. We found that females can conceive early (approx. 1.5 yr of age) and had a high probability (approx. 0.8) of breeding in consecutive years, until age 13.5 years, when females that were non-lactating tended to stay in that state. Our results suggest senescence in reproduction and survival for females. We found little support for the effect of climatic covariates on demographic rates, perhaps because the park's current population management goals were predicated from drought-year conditions. This reintroduction has been successful, but continued culling actions will need to be employed and an adaptive management approach is warranted. Our demographic approach can be applied to other heavily managed large-ungulate systems with few or no natural predators.
Frequent False Hearing by Older Adults: The Effec ts of Predictive Context in Speech Perception

iv Introduction 1 Method 9 Results and Discussion 15 General Discussion 21 Conclusion 29 References 30 Figures 32
The solar wind interaction with Venus

The relation between Venus and the solar wind is analyzed. The effects of the intrinsic field, neutral atmosphere, and ionosphere of Venus on the solar wind are examined. The solar wind interaction phenomena is studied; consideration is given to the free-stream solar wind, bow shock, magnetosheath, boundary layer, ionospheric features, neutral atmosphere features, and wake and magnetotail. Further research on the boundary layer and tail formation, global models, and high-dynamic pressure interaction is proposed.
Using a multicore processor for rover autonomous science

Multicore processing promises to be a critical component of future spacecraft. It provides immense increases in onboard processing power and provides an environment for directly supporting fault-tolerant computing. This paper discusses using a state-of-the-art multicore processor to efficiently perform image analysis onboard a Mars rover in support of autonomous science activities.
Scientific impact of Association for Academic Surgery and Society of University Surgeons plenary session abstracts increases in the era of the Academic Surgical Congress from 2006 to 2010.

Abstract Background The objective of our study was to analyze plenary abstracts since 2006, when the Association for Academic Surgery (AAS) and Society of University Surgeons (SUS) began hosting the combined annual Academic Surgical Congress (ASC). Plenary session abstracts from the separate AAS and SUS meetings from 2002 to 2004 had previously revealed no significant difference in the scientific impact of published manuscripts. Materials and methods In total, 76 abstracts from the AAS (n = 40) and SUS (n = 36) plenary sessions at the annual ASC meetings (2006–2010) were reviewed. Publication rate, citation number, 2010 impact factor (IF), and 5-y IF were obtained. Statistical analysis was conducted using Fisher exact and Student t-tests. Results Overall, 60 (79%) of 76 ASC plenary abstracts presented between 2006 and 2010 were published in peer-reviewed journals. Analysis revealed a higher publication rate for AAS (90%) compared with SUS (67%) plenary abstracts (P = 0.02). Among the articles published, the overall mean number of total citations was 6.7, with no difference between AAS and SUS (5.9 versus 7.8, P = 0.46). The mean 2010 five-year IF for all publications was 4.6 (AAS, 4.3 versus SUS, 5.0; P = 0.54). Compared with a previous analysis from the separate meetings, the mean IF has increased for both societies at an equivalent rate of 0.4. Conclusions After the initiation of the joint ASC meeting in 2006, the SUS and AAS plenary presentations continue to exhibit high-quality research. This study supports the benefit of a joint meeting for the AAS and SUS, as it has been associated with an increasing overall scientific impact for plenary abstracts.
TRANSCRIPTIONAL ACTIVATORS DIFFER IN THEIR RESPONSES TO OVEREXPRESSION OF TATA-BOX-BINDING PROTEIN

We investigated how overexpression of human TATA-box-binding protein (TBP) affects the action of estrogen receptor (ER) and compared the response with that of other activators. When ER activates a simple promoter, consisting of a response element and either the collagenase or tk TATA box, TBP overexpression potentiates transcription. TBP potentiates only estrogen-induced and not basal transcription and does so independent of spacing between response element and TATA box. TBP overexpression also reduces autoinhibition by overexpressed ER, suggesting that one target of the autoinhibition may be TBP itself. Both AF-1 and AF-2 domains of ER are potentiated by TBP, and each domain binds TBP in vitro. Like ER, chimeric GAL4/VP16 and GAL4/Tat activators are also potentiated by TBP, as is the synergistic activation by ER and GAL4/VP16 on a complex promoter. Unlike ER, GAL4/Sp1 and GAL4/NF-I become less potent when TBP is overexpressed. Furthermore, synergy between ER and Sp1 or between ER and NF-I, whether these are supplied by transfected GAL4 fusions or by the endogenous genes, is inhibited by TBP overexpression. Thus, ER resembles VP16 in response to TBP overexpression and is different from Sp1 and NF-I, which predominate over ER in setting the response on complex promoters.
Circus Maximus: the economic gamble behind hosting the Olympics and the World Cup

The Olympics and World Cup open to great fanfare as billions of eyes focus on the host city or cities for weeks throughout the competition. What those fans miss is the $100 million spent bidding to...
Role of AT1 receptors and autonomic nervous system in mediating acute pressor responses to ANG II in anesthetized mice

Hemodynamic responses to angiotensin II and the role of AT1 and AT2 receptors and the autonomic nervous system in mediating acute responses to angiotensin II were investigated in anesthetized CD1 m...
Working sets today

A program's working set is the collection of pages (or segments) recently referenced. This concept has led to efficient methods for measuring a program's intrinsic memory demand; it has assisted in understanding program behavior; and it has been used as the basis of optimal multiprogrammed memory management. This paper outlines the argument why it is unlikely that anyone will find a cheaper nonlookahead memory policy that delivers significantly better performance. This paper is based on a longer paper that presents the arguments in greater detail [DENN78d].
REM sleep and dreaming: towards a theory of protoconsciousness

Dreaming has fascinated and mystified humankind for ages: the bizarre and evanescent qualities of dreams have invited boundless speculation about their origin, meaning and purpose. For most of the twentieth century, scientific dream theories were mainly psychological. Since the discovery of rapid eye movement (REM) sleep, the neural underpinnings of dreaming have become increasingly well understood, and it is now possible to complement the details of these brain mechanisms with a theory of consciousness that is derived from the study of dreaming. The theory advanced here emphasizes data that suggest that REM sleep may constitute a protoconscious state, providing a virtual reality model of the world that is of functional use to the development and maintenance of waking consciousness.
Simulation in Pre-departure Training for Residents Planning Clinical Work in a Low-Income Country

Introduction: Increasingly, pediatric and emergency medicine (EM) residents are pursuing clinical rotations in low-income countries. Optimal pre-departure preparation for such rotations has not yet been established. High-fidelity simulation represents a potentially effective modality for such preparation. This study was designed to assess whether a pre-departure high-fidelity medical simulation curriculum is effective in helping to prepare residents for clinical rotations in a low-income country. Methods: 43 pediatric and EM residents planning clinical rotations in Liberia, West Africa, participated in a simulation-based curriculum focused on severe pediatric malaria and malnutrition and were then assessed by survey at three time points: pre-simulation, post-simulation, and after returning from work abroad. Results: Prior to simulation, 1/43 (2%) participants reported they were comfortable with the diagnosis and management of severe malnutrition; this increased to 30/42 (71%) after simulation and 24/31 (77%) after working abroad. Prior to simulation, 1/43 (2%) of residents reported comfort with the diagnosis and management of severe malaria; this increased to 26/42 (62%) after simulation and 28/31 (90%) after working abroad; 36/42 (86%) of residents agreed that a simulation-based global health curriculum is more useful than a didactic curriculum alone, and 41/42 (98%) felt a simulator-based curriculum should be offered to all residents planning a clinical trip to a low-income country. Conclusion: High-fidelity simulation is effective in increasing residents’ self-rated comfort in management of pediatric malaria and malnutrition and a majority of participating residents feel it should be included as a component of pre-departure training for all residents rotating clinically to low-income countries.
Overview of medical applications and cardiovascular intervention

Summary form only given. Lasers play an increasing role in a broad range of medical therapies. Our group has investigated multiple laser wavelengths for a variety of applications in cardiovascular disease, ophthalmology, soft tissue surgery, stone disease and photodynamic therapy. Choosing the optimal combination of laser generator, wavelength, delivery system and desired outcomes requires a thorough understanding of the interaction between the laser energy and the tissue of interest. Determination of the optimal laser wavelength requires knowledge of the tissue absorption and scattering characteristics, the depth of penetration within the target tissue and in surrounding tissues, and the ablation threshold. Careful in vitro studies can serve as the basis for system design and choice of laser; however, testing in animal models and careful clinical trials are often required to achieve optimal results. The energy parameters for laser welding of tissue are significantly different than the energy needed for tissue ablation within blood vessels. In tissue welding, uniform energy deposition through the thickness of tissue to be welded is critical. During intra-arterial tissue ablation, precise deposition leading to small volumes of ablation are preferred in order to achieve precise control. Variability of tissue characteristics and thicknesses must be considered in both cases.
Design of Conduit System with Diverging Branches

The capability of a dynamic programming conduit design technique was expanded to cover systems with diverging branch pipelines. An interactive computer programming approach was used in optimization. Optimization design is valid with little restriction. Design applies to complete turbulent, transient, as well as laminar, flow conditions. The decision variable, pipe size, assumes only pipe sizes that are available on the market.
Justice Harlan on Criminal Procedure: Two Cheers for the Legal Process School

The standard portrait of the second Justice Harlan paints him as the voice of judicial restraint on an activist court. Justice Harlan's approach to criminal procedure cases, however, has not found favor with the Court, even though a majority of the justices for many years have shown more sympathy to the prosecution than to the defense. This article locates the decisive weakness in Harlan's approach in reliance on legislatures to reform the criminal process. If that reliance were justified, Harlan's supposition that the courts should play only an interstitial law-making role would be justified. Despite occasional exceptions, legislatures have not undertaken systematic criminal justice reforms. The modern Court has recognized this political reality, and accepted a primary, rather than secondary, law-making role for the judiciary in the criminal procedure context. The article argues that, given a more realistic assessment of institutional competence, Harlan's legal-process approach offers a better path for criminal procedure's future than the formalistic new originalism evident in some of the Court's recent decisions.
Grass Endophyte-Mediated Plant Stress Tolerance: Alkaloids and Their Functions

The Family Clavicipitaceae (Hypocreales, Ascomycota) includes saprotrophic and symbiotic species associated with insects and fungi (Cordyceps spp.) or grasses, rushes and sedges (Balansia spp., Epichloe spp., Claviceps spp.) (Bacon and White, 2000). Symbiotic interactions are a notable feature of the Clavicipitaceae and they range in a continuum from antagonism to mutualism (Schardl et al., 2004). The plant biotrophic forms within this family can be characterized based on the nature of the association with hosts, being epibiotic during part or the entire life cycle or strictly endophytic with hyphae growing intercellular in the aboveground plant parts such as leaves, stems, and culms of the host.
The Logic of Liberalism: Lorenzo de Zavala’s Transcultural Politics

In 1830 a Mexican aristocrat and politician who helped draft the Mexican Constitution of 1824 and would later go on to assist in the creation of the 1836 Texas Constitution traveled to the United States, a full year before Alexis de Tocqueville's now-famous journey. Lorenzo de Zavala's voyage began in New Orleans and led him north through Cincinnati and Pittsburgh, reaching its longitudinal apex in Quebec before returning south from New York to Philadelphia and Washington, DC. His published account of the journey Viage a los Estados-Unidos del Norte de America (Journey to the United States of North America) (1834), has two purposes, his preface tells us. First, the narrative is intended to serve as a biography of sorts, as he had previously "offered" to "publish [his] memoirs" (1). Second, and more importantly, the text is intended to give "useful lessons in politics" to the citizens of Mexico, instructing them in the "manners, customs, habits and government" of the United States, a country whose social and political institutions Mexicans have heretofore "copied so servilely" (1). The tension between Zavala's desire to impart "useful lessons" yet not have those lessons learned too well, too "servilely," implies a search for a foundational politics: a liberal praxis that emerges not from the US, but also not necessarily (as we will see) from Mexico. And while Zavala's text does engage political topics and explore the possibility of a transamerican liberalism, it does so in a very specific context. Despite its stated goal of conferring "useful lessons in politics," the work is first and foremost a travel narra-
Pakistan's bomb-making capacity

The gas centrifuge enrichment plant at Kahuta, Pakistan could be producing barely enough material to make one nuclear weapon per year, or as many as 12, depending on the material used and the number of working centrifuges.
Attempt to stimulate lymphatic gland changes of fowl typhoid with adrenal cortex extract.

SummaryDaily levels of ACE for 6 days in amounts of 0.25 to 3 ml caused a significant reduction in weight of the thymus and the bursa of Fabricius. Two ml daily were adequate to cause both the weight loss and histological changes occurring in the bursa of Fabricius from chickens with fowl typhoid. Other significant changes observed for the groups given 1,2, and 3 ml daily included: decrease in body weight, increase in relative pituitary weight, reduction in adrenal weight (less cortical tissue), and increase in liver weight which bore a linear relationship with the level of ACE administration.
Relationship between Hydrocarbon Accumulation Stage and Hydrocarbon Generation and Expulsion Stage in Futai Oilfield

A chemical kinetic model is developed for calibrating organic matter-generating oil and gas of Sha-3 member shale in Jiyang depression by using data from thermal simulation experiments.The profiles of hydrocarbon generation and expulsion in Chexi sub-sag are analyzed,and the concepts of threshold of oil generation,peak oil generation and threshold of hydrocarbon expulsion are discussed in detail.Based on these,the quantitative evaluation of the history of hydrocarbon generation and expulsion for three possible source rocks in Chexi sub-sag is conducted,indicating that the hydrocarbon expulsion time took place mainly in late or recent period since the deposition of Dongying formation in Chexi Sha-3 member that is the dominant oil sources in buried hill area.This is completely consistent with the period of fluid migration and accumulation determined by inclusion's uniform temperature.Thereby,the cognitions about the periods of hydrocarbon generation,expulsion and accumulation are validated one another.
Discussion of Definitive Test Excitation Signals for Dynamic Error of Intelligent Electric Meter

In order to research the dynamic error characteristic of intelligent electric meter, the characteristics in both time and frequency domain of definitive excitation signals which include variable amplitude dynamic load excitation signal, variable frequency dynamic load excitation signal and variable phase dynamic load excitation signal are analyzed in this paper. These signals are compared respectively from the following four aspects: amplitude changes rate of excitation signal, frequency components of excitation current and instantaneous power, excitation pattern under dynamic load and the ease of excitation signal control. The results show that the trapezoid envelope excitation current signal is more appropriate to test the dynamic error of intelligent electric meter than other excitation signals.
Acidocalcisomes in Toxoplasma gondii tachyzoites

Toxoplasma gondii tachyzoites were loaded with the fluorescent indicator fura 2 to investigate the transport mechanisms involved in maintaining their intracellular Ca2+ homoeostasis. The mitochondrial ATPase inhibitor oligomycin and the endoplasmic-reticulum Ca(2+)-ATPase inhibitor thapsigargin increased the intracellular Ca2+ concentration ([Ca2+]i), thus indicating the requirement for ATP and the involvement of the endoplasmic reticulum in maintaining intracellular Ca2+ homoeostasis. The effect of thapsigargin was more accentuated in the presence of extracellular Ca2+, clearly showing that, as occurs with other eukaryotic cells, depletion of intracellular Ca2+ pools led to an increase in the uptake of Ca2+ from the extracellular medium. In addition to these results, we found evidence that, in contrast with what occurs in mammalian cells, T. gondii tachyzoites possess a significant amount of Ca2+ stored in an acidic compartment, termed the acidocalcisome, as indicated by: (1) the increase in [Ca2+]i induced by bafilomycin A1 (a specific inhibitor of H(+)-ATPases), nigericin (a K+/H+ exchanger) or the weak base NH4Cl, in the nominal absence of extracellular Ca2+ to preclude Ca2+ entry; and (2) the effect of ionomycin, a Ca(2+)-releasing ionophore that cannot take Ca2+ out of acidic organelles and that was more effective after alkalinization of these compartments by addition of bafilomycin A1, nigericin or NH4Cl. Considering the relative importance of the ionomycin-releasable and the ionomycin + NH4Cl-releasable Ca2+ pools, it is apparent that T. gondii tachyzoites contain a significant amount of Ca2+ stored in acidocalcisomes.
Linear dependence of surface expansion speed on initial plasma temperature in warm dense matter.

Recent progress in laser-driven quasi-monoenergetic ion beams enabled the production of uniformly heated warm dense matter. Matter heated rapidly with this technique is under extreme temperatures and pressures, and promptly expands outward. While the expansion speed of an ideal plasma is known to have a square-root dependence on temperature, computer simulations presented here show a linear dependence of expansion speed on initial plasma temperature in the warm dense matter regime. The expansion of uniformly heated 1–100 eV solid density gold foils was modeled with the RAGE radiation-hydrodynamics code, and the average surface expansion speed was found to increase linearly with temperature. The origin of this linear dependence is explained by comparing predictions from the SESAME equation-of-state tables with those from the ideal gas equation-of-state. These simulations offer useful insight into the expansion of warm dense matter and motivate the application of optical shadowgraphy for temperature measurement.
Smart finance for smart places to foster new venture creation

This study examines the role of smart finance within smart regions to generate smart growth. The smart growth idea has been established by the development of the 20–20 agenda of the European Commission as a regional and urban policy-prioritization framework. We follow this framework of smart growth and rely on the efficacy of the role played by entrepreneurship in driving innovation as being central to the issue. In particular, we argue that new venture creation is shaped by the interplay or ‘match’ between the smartness of a region and the provision of smart finance. Based on metropolitan areas in Germany, our empirical analysis strongly supports the complementary effect of measures of smart finance and the smartness of places in stimulating new venture creation.
Theoretical, Critical, and Practical Reflections on the Long-Term Maintenance of Health Behavior Change.

This commentary is in response to Joseph, Daniel, Thind, Benitez and Pekmezi (2014). They reviewed randomized controlled trials (RCTs) that included long-term follow-up assessments at least 6 months post-intervention. Their main purpose was to understand which theory or model used by researchers could help explain the long-term maintenance of health behaviors once the intervention was withdrawn in trials focused on physical activity, dietary behavior, and excessive alcohol consumption. Results showed that social cognitive theory (SCT) and transtheoretical model (TTM) were used most often and associated with long-term behavior change compared to self-determination theory (SDT), theory of planned behavior (TPB), or the social-ecological model (SEM). SDT showed encouraging findings while the evidence was unclear for the TPB and the SEM. Here it is argued that scientists should continually reflect on the utility of theory over time and the efforts by Joseph and colleagues should be commended. It is also usefu...
First-Principles Study of Nonradiative Recombination in Silicon Nanocrystals: The Role of Surface Silanol

The photophysical properties of emissive silicon nanomaterials depend strongly on the chemical composition and structure of their surfaces, and the development of a causal, microscopic understanding of this relationship is highly desirable. One surface-dependent property of interest is the propensity for nonradiative recombination (NRR). In this work, we apply ab initio theoretical methods to investigate the mechanism of NRR in a silicon nanocrystal with a single surface silanol group. Ab initio multiple spawning simulations of an electronically excited cluster model (Si7H11OH) indicate ultrafast nonradiative decay to the electronic ground state. A multireference electronic structure study demonstrates that this nonradiative decay occurs near conical intersections between the ground and first excited electronic states of the cluster. These intersections are accessed after stretching of the bond between the silanol silicon atom and an adjacent silicon atom. The presence of this intersection in a true nanom...
Echocardiographic Studies of the Tricuspid Valve in Atrial Septal Defect

Echocardiography has been well established as a non-invasive tool in the evaluation of congenital heart disease. The information derived from recording of the mitral and aortic valves has been used in the diagnosis of various cardiovascular entities.1–3 The tricuspid valve, on the other hand, is not recorded easily and has not been well studied. In this report we describe the frequency of occurrence of diastolic fluttering of the tricuspid valve in 22 patients with atrial septal defect and relate it to the volume of the left to right shunt.
Effect of American College of Surgeons Trauma Center Designation on Outcomes: Measurable Benefit at the Extremes of Age and Injury.

Background American College of Surgeons (ACS) verification is believed to provide benefits for trauma patients, but is associated with direct costs. Study Design We performed a 1-year retrospective review of the National Trauma Data Bank (NTDB) for 2012. Patients were separated into 3 age groups; Pediatric (PEDS), 0 to 14 years; adult, 15 to 65 years; and elderly (ELD), older than 65 years. We analyzed 2 injury severity cohorts, Injury Severity Score (ISS) 9 to 74 (ALL) and ISS 25 to 74 (MAJ). Multiple logistic regression to determine significance of ACS verification on mortality and major complications, controlling for age, ISS, shock, Glasgow Coma Scale, sex, age, comorbidities, and mechanism. Patients were excluded with an ISS Results There were 392,997 patients: 262,644 in ACS centers and 130,353 in non-ACS centers. Distribution was: PEDS 3.8%, adults 64.5%, ELD 31.7%. For ALL adults, no differences were observed for primary outcome in ACS vs non-ACS centers (p = 0.128 and 0.061, for mortality and complications, respectively). For ALL PEDS and ELD, complications were more likely in non-ACS centers: (p = 0.003, odds ratio [OR] 2.61 [95% CI 1.36 to 5.0], and p Conclusions Measurable benefits in complications were observed in all age groups with MAJ trauma and in PEDS and ELD for ALL injury severity in ACS vs non-ACS trauma centers.
Omnibus Academic Conference: The Socratic Method

This final chapter provides an opportunity to reflect upon the work we have witnessed Socrates perform on his students, psychology, and us. At this Conference, we draw together the important practical aspects of the Socratic Method which have now been deepened through our contact with nearly a dozen Socratic dialogues.
Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy

Abstract Objective Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS). Methods KEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45 mg/day), transdermal 17β estradiol (t-E2, 50 μg/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences. Results During treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments. Conclusions Although OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol. Clinical Trial Registration for KEEPS: NCT00154180
On the vulnerability of multi-level communication network under catastrophic events

Various cyber-physical infrastructures such as communication networks and power grids are known to be vulnerable to large-scale stressors ranging from natural disasters to intentional attacks such as those effected by weapons of mass destruction and high-altitude electromagnetic pulses. The stresses instigated by these events can cause damage to critical components of the network infrastructure. In this paper, a general probabilistic model is developed for assessing the vulnerability of a communication network under various catastrophic events. A multi-level scalable network framework is proposed to capture the inter-dependencies across various communication networks in the infrastructure. For a given large-scale stressor, the initial-failure probability of each network component is formulated independently and then by taking into account the failure of the components that it depends upon. This enables the modeling of a shared failure among network components. Detailed simulations of a three-level network model are performed and key network-performance metrics are computed including the total network capacity, the maximum flow and the number of node failures. This work paves the way to model and evaluate the reliability of critical communication networks under massive stressor events.
Enhanced Intratumoral Delivery of SN38 as a Tocopherol Oxyacetate Prodrug Using Nanoparticles in a Neuroblastoma Xenograft Model

Purpose: Currently, <50% of high-risk pediatric solid tumors like neuroblastoma can be cured, and many survivors experience serious or life-threatening toxicities, so more effective, less toxic therapy is needed. One approach is to target drugs to tumors using nanoparticles, which take advantage of the enhanced permeability of tumor vasculature.Experimental Design: SN38, the active metabolite of irinotecan (CPT-11), is a potent therapeutic agent that is readily encapsulated in polymeric nanoparticles. Tocopherol oxyacetate (TOA) is a hydrophobic mitocan that was linked to SN38 to significantly increase hydrophobicity and enhance nanoparticle retention. We treated neuroblastomas with SN38-TOA nanoparticles and compared the efficacy with the parent prodrug CPT-11 using a mouse xenograft model.Results: Nanoparticle treatment induced prolonged event-free survival (EFS) in most mice, compared with CPT-11. This was shown for both SH-SY5Y and IMR-32 neuroblastoma xenografts. Enhanced efficacy was likely due to increased and sustained drug levels of SN38 in the tumor compared with conventional CPT-11 delivery. Interestingly, when recurrent CPT-11-treated tumors were re-treated with SN38-TOA nanoparticles, the tumors transformed from undifferentiated neuroblastomas to maturing ganglioneuroblastomas. Furthermore, these tumors were infiltrated with Schwann cells of mouse origin, which may have contributed to the differentiated histology.Conclusions: Nanoparticle delivery of SN38-TOA produced increased drug delivery and prolonged EFS compared to conventional delivery of CPT-11. Also, lower total dose and drug entrapment in nanoparticles during circulation should decrease toxicity. We propose that nanoparticle-based delivery of a rationally designed prodrug is an attractive approach to enhance chemotherapeutic efficacy in pediatric and adult tumors. Clin Cancer Res; 24(11); 2585-93. ©2018 AACR.
Study of an Extensive Set of Eye Movement Features: Extraction Methods and Statistical Analysis.

This work presents a study of an extensive set of 101 categories of eye movement features from three types of eye movement events: fixations, saccades, and post-saccadic oscillations. We present a unified framework of methods for the extraction of features that describe the temporal, positional and dynamic characteristics of eye movements. We perform statistical analysis of feature values by employing eye movement data from a normative population of 298 subjects, recorded during a text reading task. We present overall measures for the central tendency and variability of feature values, and we quantify the test-retest reliability of features using either the Intraclass Correlation Coefficient (for normally distributed and normalized features) or Kendall’s coefficient of concordance (for non-normally distributed features). Finally, for the case of normally distributed and normalized features we additionally perform factor analysis and provide interpretations of the resulting factors. The presented methods and analysis can provide a valuable tool for researchers in various fields that explore eye movements, such as in behavioral studies, attention and cognition research, medical research, biometric recognition, and human-computer interaction.
A Maieutic Exploration of Nudging Strategies for Regional Climate Applications Using the WRF Model

AbstractThe use of nudging in WRF to constrain regional climate downscaling simulations is gaining in popularity because it can reduce error and improve consistency with the driving data. While some attention has been paid to whether nudging is beneficial for downscaling, very little research has been performed to determine best practices. In fact, many published papers use the default nudging configuration (which was designed for NWP), follow practices used by colleagues, or adapt methods developed for other regional climate models.Here, a suite of 45 three-year simulations is conducted with WRF over the continental United States to systematically and comprehensively examine a variety of nudging strategies. The simulations here use a longer test period than previously published works to better evaluate the robustness of each strategy through all four seasons, through multiple years, and across nine regions of the United States. The analysis focuses on the evaluation of 2-m temperature and precipitation, ...
Five Theses for Interactive Digital Narrative

The field of Interactive Digital Narrative (IDN) can look back at more than 25 years of research. Considerable technical advances exist alongside open questions that still need full attention. With the discussion of five crucial aspects - narrative analysis, interoperability between different implementations, sustainability of digital artifacts, author-centered view, and user-focused perspective - the paper starts a conversation on successful methods and future goals in the research field.
Immunosuppressive Drug Monitoring: Limitations of Immunoassays and the Application of Liquid Chromatography Mass Spectrometry

Immunosuppressive drug monitoring is required for optimizing individualized therapeutic effectiveness and minimizing serious adverse events. To accomplish this, precise and robust analytical methods are required for quantitating blood concentrations of cyclosporine, tacrolimus, sirolimus, mycophenolic acid and, more recently, everolimus. The majority of laboratories in the United States measure immunosuppressive drugs by immunoassay, despite significant metabolite cross-reactivity that can be extremely variable, depending on organ type and post-transplant time. Liquid chromatography separation coupled with mass spectrometry detection methods offer unparalleled sensitivity, specificity and versatility for monitoring immunosuppressive drugs, but are typically only utilized by large laboratories. Immunoassays are popular because they are automated, have low start-up costs, and are easy to perform without the need for specially trained technologists. In view of the increasing cost of immunoassay reagents, liquid chromatography with mass spectrometry detection systems are rapidly becoming a good investment for monitoring immunosuppressive drugs.
Stochastic Control of Power Supply in Data Centers

The problem of operating the power supply system of a data center in a reliable manner is studied. Two approaches are examined. The first one assumes that there is no control over the power supply system. The second one assumes that there is a control over the maximum capacity of the system load. For the second case, the problem is fitted into a dynamic programming (DP) framework. An optimal control policy is derived, however is intractable. An approximate solution is then constructed by the Perseus algorithm. This solution is compared to two easily implementable heuristic algorithms, and with the case where no system control is allowed. Numerical results show that the approximate solution has a superior performance.
A Cancer-Specific Ubiquitin Ligase Drives mRNA Alternative Polyadenylation by Ubiquitinating the mRNA 3' End Processing Complex.

Summary Alternative polyadenylation (APA) contributes to transcriptome complexity by generating mRNA isoforms with varying 3′ UTR lengths. APA leading to 3′ UTR shortening (3′ US) is a common feature of most cancer cells; however, the molecular mechanisms are not understood. Here, we describe a widespread mechanism promoting 3′ US in cancer through ubiquitination of the mRNA 3′ end processing complex protein, PCF11, by the cancer-specific MAGE-A11–HUWE1 ubiquitin ligase. MAGE-A11 is normally expressed only in the male germline but is frequently re-activated in cancers. MAGE-A11 is necessary for cancer cell viability and is sufficient to drive tumorigenesis. Screening for targets of MAGE-A11 revealed that it ubiquitinates PCF11, resulting in loss of CFIm25 from the mRNA 3′ end processing complex. This leads to APA of many transcripts affecting core oncogenic and tumor suppressors, including cyclin D2 and PTEN. These findings provide insights into the molecular mechanisms driving APA in cancer and suggest therapeutic strategies.
Genomics-guided drawing of malignant regulatory signatures revealed a pivotal role of human stem cell-associated retroviral sequences (SCARS) and functionally-active hESC enhancers

From patients and physicians perspectives, the clinical definition of a tumor malignant phenotype could be restricted to the early diagnosis of sub-types of malignancies with the increased risk of existing therapy failure and high likelihood of death from cancer. It is the viewpoint from which the understanding of malignant regulatory signatures is considered in this contribution. Analyses from this perspective of experimental and clinical observations revealed the pivotal role of human stem cell-associated retroviral sequences (SCARS) in the origin and pathophysiology of clinically-lethal malignancies. SCARS represent evolutionary- and biologically-related family of genomic regulatory sequences, the principal physiological function of which is to create and maintain the stemness phenotype during human preimplantation embryogenesis. SCARS expression must be silenced during cellular differentiation and SCARS activity remains silent in most terminally-differentiated human cells performing specialized functions in the human body. De-repression and sustained activation of SCARS result in differentiation-defective phenotypes, tissue- and organ-specific clinical manifestations of which are diagnosed as pathological conditions defined by a consensus of pathomorphological, molecular, and genetic examinations as the malignant growth. Contemporary evidence are presented that high-fidelity molecular signals of continuing activities of SCARS in association with genomic regulatory networks of thousands functionally-active enhancers triggering engagements of down-stream genetic loci may serve as both reliable diagnostic tools and druggable molecular targets readily amenable for diagnosis and efficient therapeutic management of clinically-lethal malignancies.
Abstract 3754: PPP6C regulation of ERK signaling in melanoma

Melanoma, the deadliest form of skin cancer, is characterized by aberrant hyperactivation of the ERK mitogen-activated protein kinase signaling pathway. Inhibitors of BRAF and MEK1/2, both members of this pathway, have shown clinical efficacy and are used in combination to treat BRAFV600E melanoma, the most common melanoma genomic subtype. However, not all BRAFV600E melanomas respond to these inhibitors, and those that do respond eventually acquire resistance. To better understand mechanisms of drug susceptibility in BRAFV600E melanoma, we performed a loss-of-function screen to identify kinases and phosphatases that modulate sensitivity to two clinical MEK1/2 inhibitors. In this screen, we identified PPP6C, the catalytic subunit of protein phosphatase 6 (PP6), as a factor promoting sensitivity to MEK1/2 inhibition. PPP6C is a potential tumor suppressor mutated in 7-12% of melanomas, and has roles in cell cycle regulation and DNA damage repair. shRNA-mediated knockdown and CRISPR/Cas9-mediated knockout of PPP6C in BRAF mutant melanoma cells both lead to hyperactivation of MEK1/2 and ERK1/2, resulting in decreased sensitivity to pathway inhibitors. This finding was confirmed in a panel of BRAFV600E melanoma cell lines. Through in vitro biochemical and cell-based studies, we have established that PP6 directly dephosphorylates MEK1/2. As with complete loss of PPP6C, cells expressing most recurrent cancer-associated PPP6C mutants similarly have hyperactive ERK signaling. Our studies support a novel negative regulatory role for PPP6C in ERK signaling that contributes to its activity as a tumor suppressor and promotes pathway inhibitor sensitivity in BRAFV600E melanoma. Citation Format: Eunice Cho, Hua Jane Lou, Benjamin E. Turk. PPP6C regulation of ERK signaling in melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3754.
Twitter-based analysis reveals differential COVID-19 concerns across areas with socioeconomic disparities.

Abstract Objective We sought to understand spatial-temporal factors and socioeconomic disparities that shaped U.S. residents’ response to COVID-19 as it emerged. Methods We mined coronavirus-related tweets from January 23rd to March 25th, 2020. We classified tweets by the socioeconomic status of the county from which they originated with the Area Deprivation Index (ADI). We applied topic modeling to identify and monitor topics of concern over time. We investigated how topics varied by ADI and between hotspots and non-hotspots. Results We identified 45 topics in 269,556 unique tweets. Topics shifted from early-outbreak-related content in January, to the presidential election and governmental response in February, to lifestyle impacts in March. High-resourced areas (low ADI) were concerned with stocks and social distancing, while under-resourced areas shared negative expression and discussion of the CARES Act relief package. These differences were consistent within hotspots, with increased discussion regarding employment in high ADI hotspots. Discussion Topic modeling captures major concerns on Twitter in the early months of COVID-19. Our study extends previous Twitter-based research as it assesses how topics differ based on a marker of socioeconomic status. Comparisons between low and high-resourced areas indicate more focus on personal economic hardship in less-resourced communities and less focus on general public health messaging. Conclusion Real-time social media analysis of community-based pandemic responses can uncover differential conversations correlating to local impact and income, education, and housing disparities. In future public health crises, such insights can inform messaging campaigns, which should partly focus on the interests of those most disproportionately impacted.
Evaluating Response Shift in Statistical Mediation Analysis

Researchers and prevention scientists often develop interventions to target intermediate variables (known as mediators) that are thought to be related to an outcome. When researchers target a media...
FORVAL: computer software package for agricultural and natural resources investment analysis.

The valuation of agricultural and natural resource investments presents challenging analysis problems that often require the use of computer software. Most of these computer packages are complex and costly. FORVAL is a free, user-friendly, menu-driven, agricultural and natural resource investment analysis package. It can accommodate any investment scenario and includes the standard financial criteria (net present value, rate of return, equal annual income, benefit/cost ratio, and land expectation value for forestry investments). FORVAL accommodates various cash flows like single sum, terminating annual and periodic series, and perpetual annual and periodic series. It also has options for payment and price projections.