cssi/SciSciGPT-SciSciNet huggingface dataset:
A Novel Allele of Saccharomyces cerevisiae NDC1 Reveals a Potential Role for the Spindle Pole Body Component Ndc1p in Nuclear Pore Assembly

Both the spindle pole body (SPB) and the nuclear pore complex (NPC) are essential organelles embedded in the nuclear envelope throughout the life cycle of the budding yeast Saccharomyces cerevisiae. However, the mechanism by which these two multisubunit structures are inserted into the nuclear envelope during their biogenesis is not well understood. We have previously shown that Ndc1p is the only known integral membrane protein that localizes to both the SPBs and the NPCs and is required for SPB duplication. For this study, we generated a novel temperature-sensitive (ts) allele of NDC1 to investigate the role of Ndc1p at the NPCs. Yeast cells carrying this allele (ndc1-39) failed to insert the SPB into the nuclear envelope at the restrictive temperature. Importantly, the double mutation of ndc1-39 and NPC assembly mutant nic96-1 resulted in cells with enhanced growth defects. While nuclear protein import and NPC distribution in the nuclear envelope were unaffected, ndc1-39 mutants failed to properly incorporate the nucleoporin Nup49p into NPCs. These results provide evidence that Ndc1p is required for NPC assembly in addition to its role in SPB duplication. We postulate that Ndc1p is crucial for the biogenesis of both the SPBs and the NPCs at the step of insertion into the nuclear envelope.
Does Place of Residence Matter? Rural–Urban Differences and the Wellbeing of Gay Men and Lesbians

Does place of residence matter for gay men and lesbians? Both conventional wisdom and scholarly literature suggests that it does, and that those living in rural areas are disadvantaged relative to their urban peers. This study explores this issue by comparing gay people's wellbeing in rural and urban areas. Results from a large probability sample show that rural gay people fare no worse than their urban peers. If anything, results suggest living in the largest cities may be detrimental to gay people's wellbeing, although more so for lesbians than for gay men. Results are discussed in light of 4 competing perspectives on rural-urban differences.
Nonlinear irreversible fluxes in a fluid with large shear rate

Generalized Green-Kubo expressions are used to describe the nonlinear dependence of the irreversible heat and momentum fluxes on the thermodynamic forces for a simple fluid. Formally exact equations for these fluxes are evaluated for conditions of large shear flow. The associated non-equilibrium time correlation functions are evaluated exactly to linear order in the temperature and pressure gradients, and to arbitrary order in the shear rate, for a low-density gas of Maxwell molecules. Modifications of Fourier's heat law and Newton's viscosity law are obtained in terms of transport coefficients that depend on the shear rate. This dependence on shear rate is illustrated for several of the transport coefficients.
Biogenic Versus Anthropogenic Sources of CO in the United States

Aircraft observations of carbon monoxide (CO) from the ICARTT campaign over the eastern United States in summer 2004 (July 1–August 15), interpreted with a global 3-D model of tropospheric chemistry (GEOS-Chem), show that the national anthropogenic emission inventory from the U.S. Environmental Protection Agency (93 Tg CO y−1) is too high by 60% in summer. Our best estimate of the CO anthropogenic source for the ICARTT period is 6.4 Tg CO, including 4.6 Tg from direct emission and 1.8 Tg CO from oxidation of anthropogenic volatile organic compounds (VOCs). The biogenic CO source for the same period from the oxidation of isoprene and other biogenic VOCs is 8.3 Tg CO, and is independently constrained by ICARTT observations of formaldehyde (HCHO). Anthropogenic emissions of CO in the U.S. have decreased to the point that they are now lower than the biogenic source in summer.
Review of Shane Darcy, Collective Responsibility and Accountability Under International Law (Procedural Aspects of International Law Monograph Series)

In The Competing Jurisdictions of International Courts and Tribunals, Yuval Shany offers a structural analysis of public international fora. The book,recently awarded the Certificate of Merit Award by the American Society ofInternational Law, is the adaptation of Shany’s doctoral dissertation written under Professor Philippe Sands at the University of London (SOAS). The book could not have been written too soon. The increasing number ofinternational legal sources and institutions has not corresponded to theproliferation of international procedural law regarding jurisdiction. On thecontrary, international courts and tribunals have had to assess the scopes of their own judicial authority on an ad hoc basis in a process that hasbeen termed ‘fragmentation.’ This makes Shany’s contribution an especially welcome analysis of the currently overlapping jurisdictions of internationalfora.
Environmental Factors Affecting Female Infertility

There is increasing concern about the effects of environmental contaminants on reproductive health. While there are limited clinical data regarding most chemical exposures and human reproduction, studies in laboratory animal models and wildlife under- score the vulnerability of the reproductive system to many environmental insults at different times of development and across the life cycle. Here, we review data implicating select environmental contaminants in compromised reproductive capacity in animals. We also review epidemiologic data in humans that suggest roles for environmental contaminants in reproductive dysfunction and infertility.
Association of Digoxin With Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset.

Background Mortality for infants with single ventricle congenital heart disease remains as high as 8% to 12% during the interstage period, the time between discharge after the Norwood procedure and before the stage II palliation. The objective of our study was to determine the association between digoxin use and interstage mortality in these infants. Methods and Results We conducted a retrospective cohort study using the Pediatric Heart Network Single Ventricle Reconstruction Trial public use dataset, which includes data on infants with single right ventricle congenital heart disease randomized to receive either a Blalock‐Taussig shunt or right ventricle‐to‐pulmonary artery shunt during the Norwood procedure at 15 institutions in North America from 2005 to 2008. Parametric survival models were used to compare the risk of interstage mortality between those discharged to home on digoxin versus those discharged to home not on digoxin, adjusting for center volume, ascending aorta diameter, shunt type, and socioeconomic status. Of the 330 infants eligible for this study, 102 (31%) were discharged home on digoxin. Interstage mortality for those not on digoxin was 12.3%, compared to 2.9% among those on digoxin, with an adjusted hazard ratio of 3.5 (95% CI, 1.1–11.7; P =0.04). The number needed to treat to prevent 1 death was 11 patients. There were no differences in complications between the 2 groups during the interstage period. Conclusions Digoxin use in infants with single ventricle congenital heart disease is associated with significantly reduced interstage mortality.
Structural Equation Modeling

Structural equation modeling (SEM) is a multivariate statistical framework that is used to model complex relationships between directly observed and indirectly observed (latent) variables. SEM is a general framework that involves simultaneously solving systems of linear equations and encompasses other techniques such as regression, factor analysis, path analysis, and latent growth curve modeling. Recently, SEM has gained popularity in the analysis of complex genetic traits because it can be used to better analyze the relationships between correlated variables (traits), to model genes as latent variables as a function of multiple observed genetic variants, and to assess the association between multiple genetic variants and multiple correlated phenotypes of interest. Though the general SEM framework only allows for the analysis of independent observations, recent work has extended SEM for the analysis of data on general pedigrees. Here, we review the theory of SEM for both unrelated and family data, describe the available software for SEM, and provide examples of SEM analysis.
Agents of Change: Soviet Advisers and High Stalinist Management in China, 1949–1960

This article chronicles the interactions between the Soviet Union and the People's Republic of China (PRC) during the years of the Sino-Soviet alliance (1949–1960) as experienced by the Soviet advisers in China. Based on interviews, archival sources, and other materials, the article shows that the Soviet advisers who came to the PRC during that time brought with them the management techniques of the late Stalin period, known as High Stalinism (meaning strict Communist Party control over all aspects of political, cultural, and economic life and severe management methods including a heavy reliance on mass methods, education and reeducation techniques, coercion, and the threat of imprisonment). High Stalinism was a useful management tool that fit into Mao Zedong's own plan for the “economic Stalinization” of China and helped to pave the way for Mao's later radicalization. After differences emerged between the two countries in 1956 about the merits of de-Stalinization, Mao and the Chinese Communist Party bega...
Social well-being.

The proposal of five dimensions of social well-being, social integration, social contribution, social coherence, social actualization, and social acceptance, is theoretically substantiated. The theoretical structure, construct validity, and the social structural sources of the dimensions of social well-being are investigated in two studies. Item and confirmatory factor analyses in both studies corroborate the theoretical model of social well-being. The new scales correlate convergently with measures of anomie, generativity, perceived social constraints, community involvement and neighborhood quality. The new scales correlate discriminantly with measures of dysphoria, global well-being, physical health and optimism. Multivariate analyses in both studies substantiate the claim that social well-being is an achievement, facilitated by educational attainment and age. The state and direction of the study of adult functioning are discussed.
A Look at the Use of VIX Futures in Investment Portfolios: Buy-and-Hold versus Tactical Allocations

This article demonstrates the general relationship of VIX futures, which trade on the CBOE Futures Exchange, to the underlying VIX index, as compiled by the CBOE, and how VIX futures might diversify and enhance a standard portfolio of equity and fixed income. The authors examine the use of VIX futures in a number of portfolio allocations over the period 2005-2009 and show that using VIX futures in a buy-and-hold strategy is not likely to be prudent in most scenarios. That does not indicate, however, that VIX futures should be disregarded completely. One beneficial use, examined here, uses VIX futures in a tactical manner that takes advantage of both the trend of the VIX futures as well as their tendency to increase when stocks decline. The key to these contracts is to understand how they trade, analyze them independently from the VIX index, and closely monitor their performance within any portfolio in which they are used.
Radiation therapy in management of breast cancer

Randomized trials have demonstrated the efficacy of radiation therapy in the treatment of breast cancer. A reduction in the risk of recurrence has been shown in breast conservation for ductal carcinoma in situ and in invasive cancers after breast conservation and mastectomy. The importance of local control in breast cancer is becoming more apparent. Defining the groups of patients who most benefit from the therapy and improving treatment delivery systems to enhance the therapeutic index are ongoing challenges.
The Study for Chinese Railwaymen’s Psychological Capital Characteristic

Objective and Methods 156 Chinese train drivers and train-attendants were recruited for the study of their Psychological Capital,Hope,Resilience,and Optimism.Results and Conclusions ①There were significant differences of Psychological Capital on the variables of Job Categories,Comment on Own Income,and Education Level.② No differences were found on psychological capital between men and women.③ Between Comment on Own Income and Hope there is significant positive correlation.
Efficiency of hydrocyclone separation technology when dealing with overflow sewage

The effect of hydrocyclone separation technology on kaolin solution,sediment water and overflow sewage treatment were studied respectively.The results showed that,the removal rates of pollutants increased with the increase of the inlet pressure,the stability of the inlet pressure could directly affect the separating effect of the hydrocyclone.The results of the productive test indicated that,using the said technology to treat the overflow sewage at the initial stage,the average removal rates of CODCr and SS reached 35.2% and 47.4% respectively,the discharge amount of pollutants was greatly reduced.
Induced Seismicity and Carbon Storage: Risk Assessment and Mitigation Strategies

1 1. INTRODUCTION 2 2. SCIENTIFIC AND TECHNICAL BACKGROUND 5 2.1 BASIC SEISMICITY CONCERNS 5 2.2 EVENT CHAIN VIEW OF SEISMIC IMPACTS 9 2.3 SITE CHARACTERISTICS 10 2.4 SEISMIC MONITORING 17 2.5 EARTHQUAKE STATISTICS 22 3. RISK MANAGEMENT FOR INDUCED SEISMICITY 26 3.1 A PHASED APPROACH TO RISK ASSESSMENT 26 3.2 PROBABILISTIC SEISMIC RISK ASSESSMENT 29 3.3 PROBABILISTIC LEAKAGE RISK ASSESSMENT 38 4. RECOMMENDATIONS 41 5. REFERENCES 44 Induced Seismicity and Carbon Storage: Risk Assessment and Mitigation Strategies
Local Officials Say Michigan's System of Funding Local Government is Broken, and Seek State Action to Fix it

This report presents views of Michigan’s local government leaders regarding the state’s system of funding local government, whether it needs to be reformed, and what reforms they prefer. It also includes their preferences for raising additional local revenues if given the opportunity to levy local-option taxes. The findings are based on responses to statewide surveys of local government leaders in the Spring 2016 wave of the Michigan Public Policy Survey (MPPS).
Simulation optimization via promising region search and surrogate model approximation

We propose a random search algorithm for solving simulation optimization problems with continuous decision variables. The algorithm combines ideas from promising area search, shrinking ball methods, and surrogate model optimization. We discuss the local convergence property of the algorithm and provide numerical examples to illustrate its performance.
Stochastic Integer Programming in Healthcare Delivery

This chapter reviews different ways that stochastic integer programming has been used to improve efficiency and efficacy in healthcare delivery. For the purpose of this study healthcare delivery is divided into two areas: resource allocation and operations. In each area the stochastic components are identified and the algorithms and solution techniques that have been proposed in the literature are described. We conclude the discussion with the current challenges and open questions.
Cause or Effect? Validating the Use of Tests for High-Stakes Inferences in Education

A good aphorism can, in a few words, capture an essential truth. Of the many good aphorisms Paul Holland has coined over the years, I have found myself invoking the one above frequently enough to worry that I should be paying out royalty fees, so it is only fitting that I use it as the starting point for some ideas I wish to explore in this paper.
TFCC Injuries: Meta-Analysis and Comparison of Diagnostic Imaging Modalities.

Background Imaging of the triangular fibrocartilaginous complex (TFCC) remains difficult, as no single imaging modality demonstrates perfect sensitivity and specificity. Purpose This study performs a meta-analysis of multiple previous publications to guide noninvasive imaging selection for the diagnosis of TFCC injuries. Methods A literature search was performed and conducted. Studies were included that compared the diagnostic accuracy of magnetic resonance imaging (MRI), magnetic resonance arthrography (MRA), and computed tomography (CT)/computed tomographic arthrography (CTA) for the evaluation of TFCC injuries. All studies included either arthroscopic or open surgical findings as the “gold standard.” A meta-analysis was performed comparing the diagnostic accuracy of MRA, MRI, and CT for the detection of TFCC injuries. Results Initial search returned 2,568 candidate articles. Studies were then reviewed and narrowed yielding a total of 28 independent studies (20 MRI, 9 MRA, 4 CT/CTA with some studies including multiple modalities) considered in the qualitative data synthesis. Pooling of the raw data in a meta-analysis demonstrated sensitivities of 0.76 (0.72–0.80), 0.78(0.70–0.84), and 0.89 (0.81–0.95) for MRI, MRA, and CT arthrogram, respectively, with specificities of 0.82 (0.77–0.86), 0.85 (0.77–0.92), and 0.89 (0.81–0.95), respectively. Additionally, across all imaging modalities, diagnostic accuracy was highest for central TFCC lesions versus peripheral lesions. Conclusion This study represents the largest meta-analysis to date to compare multiple imaging modalities for the diagnosis of TFCC injuries. Pooled data demonstrated that CTA and MRA had statistically equivalent sensitivity and specificity for the diagnosis of TFCC injuries. Diagnostic accuracy was highest for central TFCC injuries.
Taxes, Tablets, and Experiential Teaching

Classroom use of a tablet computer is evaluated from the perspective of the teacher’s engagement in the teaching experience. The type of tablet used, the annotation software employed, and the classroom recording software utilized in the publication of the classroom experience on Blackboard are topics discussed. The tablet computer is compared and contrasted to three other classroom delivery methods.
An experimental critique on the existence of fragile-to-strong transition in glass-forming liquids

Abstract A number of recent studies in the literature have reported the existence of unusual temperature dependence of the shear viscosity for a variety of glass-forming liquids that cannot be described with a single fragility index. Rather, these liquids display an apparent fragile-to-strong transition (FST) with lowering of temperature that was suggested to be indicative of a structural transition. In the present work we critique the accuracy of the high-temperature oscillation viscometry technique that was used almost exclusively for viscosity measurements of these liquids above their liquidus temperature. Viscosity measurements are carried out on binary Ge-Se chalcogenide liquids in their supercooled and stable states using conventional capillary and parallel-plate rheometry techniques and are compared with the oscillation viscometry data in the literature. Such comparisons conclusively demonstrate that the latter measurement technique often underestimates the viscosity by nearly an order of magnitude, especially at high temperatures. These results, when taken together, indicate that the observation of FST in glass-forming liquids is likely an artifact of the inaccuracy of the oscillation viscometry technique. Moreover, these results cast serious doubt on the reliability of the high-temperature oscillation viscometry data for metals and alloys that are prevalent in the literature.
The influence of government policies on informal labor: Implications for long-run growth

Using cross-sectional data from industrialized and developing economies, we examine long-run growth regressions linking government policies, informal employment and real GDP per worker. We find that changes in government policies of taxation and enforcement significantly affect growth in the informal sector. Further, we show that increases (decreases) in informal employment significantly and negatively (positively) affect a country's growth rate of real GDP per worker. The empirical link between government policies, informal employment and real GDP per worker holds irrespective of a country's development. On average, changes in government policies, through their effect on the size of the informal sector, account for 6 percent of the growth rate of real GDP per worker between 1960 and 1990.
Continuum Balance Equations for Multicomponent Fluids

The mixtures described in Chapter 5 are based on the concept that a mixture may be represented by “a sequence of bodies B k , all of which ...occupy regions of space ... simultaneously” [89, p. 81]. Examples of such materials are air (a mixture of nitrogen, oxygen, and other materials in small amounts), and whisky (a mixture of water, alcohol, and other materials in small amounts). However, it was commonly recognized at an early stage that so strong an assumption of intermiscibility was not appropriate to all physical situations. For example, soils, porous rock, suspensions of coal particles in water, packed powders, granular propellants, etc., consist of identifiable solid particles surrounded by one or more continuous media, or an identifiable porous matrix through which one or more of the continua are dispersed. Motions of the individual components are possible and, as long as there are no chemical reactions, each constituent retains its integrity1. We call such materials multicomponent mixtures. They are more complicated than classical mixtures in the sense that they have geometrical structure, but less complicated in the sense that the constituents are not intimately intermixed. A theory describing them should reflect these facts.
Study of local and nonlocal Poisson–Boltzmann equations for linear and nonlinear models with spherical symmetry

Abstract In this paper, the local and nonlocal Poisson–Boltzmann equations are studied on their linear and nonlinear models with spherical symmetry. In particular, the exact solutions of the linear and nonlinear modes are obtained in either analytical expressions or simplified boundary value problems, whose solutions can be found easily via the Maple procedure dsolve for example. Numerical results confirm the derived solution properties, and show that the two new linear models proposed in this paper can have higher accuracy than the two conventional linear models in approximation to the local and nonlocal nonlinear models, respectively.
Motor Effects Produced by Disruption of Basal Ganglia Output to the Thalamus

When a limb movement is made to a target, information relevant to a series of decisions or parametric values must be carried in the eventual neural output to muscles. One way to examine the role(s) of the basal ganglia in controlling movement, then, is to examine the influence of basal ganglia output on these movement-related decisions or parameters, several of which are shown diagrammatically in Figure 1.
The Litigation Environment of a Firm and its Impact on Financial Policy

Theory suggests that management may be able to increase firm value through the strategic use of debt when facing contingent liabilities. This paper examines whether managers strategically use financial policy when facing the risk of one such liability – litigation claims. I find that greater litigation exposure leads firms to choose higher leverage. I show that this leverage increase is brought on by an active decision to repurchase shares. These repurchases appear to be financed with a combination of excess cash and short term debt as they coincide with a significant decrease in cash holdings and an increase in short term liabilities. These firms also increase their use of operating leases, which, due to their priority in bankruptcy, have similar characteristics to secured debt. Finally, the effects seem to be stronger for firms with a higher probability of bankruptcy. These results run counter to anecdotal suggestions that firms may adjust financial policy to build a war chest in anticipation of litigation and they suggest that firms use capital structure strategically to increase shareholder value.
Novel 3D-/Inkjet-Printed Flexible On-package Antennas, Packaging Structures, and Modules for Broadband 5G Applications

Additively manufacturing techniques including 3D and inkjet printing is used to fabricate antenna and packaging structure at mm-wave range for 5G applications. The 3D printed flexible material, FLGR02, is applied to the flexible mm-wave packaging application. The fabrication process and material characterizations including solutions to surface treatment for ink adhesion, smooth of surface roughness, and CTE mismatch between the flexible material and the silver ink are proposed. Then the proposed process is used to fabricated a broadband 5G on-package antenna. The measured S11 of the proposed on-package antenna is smaller than -10 dB from 22.4 GHz to 30.1 GHz. Besides, the measured realized gain is larger than 5 dB from 22 GHz to 30.5 GHz. The differences of realized gain within the operational bandwidth is smaller than 3 dB. The fractional bandwidth is 29.3 %. The proposed antenna is broadband enough to cover the whole 5G band from 24.5 GHz to 29.5 GHz. The size of the antenna is 5mm×9mm which is 0.44?0 × 0.79?0. The radiation patterns within the operational band is also measured. Finally, a proof-of-concept demonstration of SoP design is fabricated.
The use of commercially available adhesive tapes to preserve cartilage and bone tissue integrity during cryosectioning

The use of fluorescent tags to monitor protein expression and to lineage-trace cells has become a standard complement to standard histological techniques in the fields of embryology, pathology and ...
Isolated acute funisitis in the absence of acute chorioamnionitis: What does it mean?

Abstract Objective Acute funisitis (AF) is most commonly associated with acute chorioamnionitis (AC) and ascending infection. The significance of cases of AF without associated AC or isolated funisitis (IF) is unknown. Our objective was to evaluate clinical and pathologic features of IF and to determine its significance. Study design This was a retrospective review of placentas of patients delivering at our institution from 1997 to 2017. Placentas with the diagnosis of IF comprised the study population and placentas without either AF or AC served as controls. Results There were 156 cases and 181 controls identified. Maternal age, gestational age, birthweight and mode of delivery were similar in both groups. 132 (84.6%) of cases of IF had meconium, with 62 (47.0%) having meconium only in the membranes, 36 (27.3%) in the membranes and cord and 34 (25.6%) in the membranes and cord with associated myonecrosis. 72 (38.7%) of controls had microscopically identified meconium, with only one (1.4%) showing meconium in the cord. None had myonecrosis (p Conclusion IF is highly associated with the presence of meconium discharge and meconium-associated myonecrosis of umbilical vessels. The inflammation in IF may be the result of damage to the muscle fibers of the cord due to meconium but additional studies are necessary to understand the significance of these findings.
Particularidades del golpe de Estado de 1930. El comienzo de la inestabilidad política nacional

The coup d'etat of 1930 has been equally an important event in national political history and a fact somewhat neglected by recent historiography. The objective of this article is to put into discussion and debate issues that gave shape and meaning to the context of instability and confrontation that characterized the Argentine history of past decades. It is intended to make a contribution that allows a better understanding of this event, trying to determine more precisely how General Uriburu managed to successfully carry out the first coup d'etat that attempted against the country's institutions and against the very foundations of a government legitimized since the polls. In this article there is a brief detail of the moments before the civic-military mobilization, referring to its main protagonists, the struggles and differences between them, the bases of support and the assumption made by the press. For its drafting, direct sources were used in the Documentary Fund of General Jose Felix Uriburu in the General Archive of the Nation, the Hemeroteca of the Congress of the Nation and the National Library of Argentina.
The mystery of the cosmic ages

While the measurements of the Hubble constant from the local distance ladder and the cosmic microwave background radiation appear to disagree, given a sufficient number of localized detections, gravitational waves may possibly shed light on the tension.
Smoothly bounded domains covering compact manifolds

We show that if a bounded domain in complex Euclidean space with $\mathcal{C}^{1,1}$ boundary covers a compact manifold, then the domain is biholomorphic to the unit ball.
Temporal dynamics of migration-linked genetic variation are driven by streamflows and riverscape permeability.

Landscape permeability is often explored spatially, but may also vary temporally. Landscape permeability, including partial barriers, influences migratory animals that move across the landscape. Partial barriers are common in rivers where barrier passage varies with streamflow. We explore the influence of partial barriers on the spatial and temporal distribution of migration-linked genotypes of Oncorhynchus mykiss, a salmonid fish with co-occurring resident and migratory forms, in tributaries to the South Fork Eel River, California, USA, Elder and Fox Creeks. We genotyped >4,000 individuals using RAD-capture and classified individuals as resident, heterozygous or migratory genotypes using life history-associated loci. Across four years of study (2014-2017), the permeability of partial barriers varied across dry and wet years. In Elder Creek, the largest waterfall was passable for adults migrating up-river 4-39 days each year. In this stream, the overall spatial pattern, with fewer migratory genotypes above the waterfall, remained true across dry and wet years (67%-76% of migratory alleles were downstream of the waterfall). We also observed a strong relationship between distance upstream and proportion of migratory alleles. In Fox Creek, the primary barrier is at the mouth, and we found that the migratory allele frequency varied with the annual timing of high flow events. In years when rain events occurred during the peak breeding season, migratory allele frequency was high (60%-68%), but otherwise it was low (30% in two years). We highlight that partial barriers and landscape permeability can be temporally dynamic, and this effect can be observed through changing genotype frequencies in migratory animals.
Abstract IA21: Elucidating and targeting mechanisms of single-cell state maintenance: From N-of-1 to N-of-1-of-1 studies

We have developed network-based methodologies for the systematic identification, validation, and pharmacologic targeting of a new class of therapeutic targets. These targets comprise Master Regulator proteins, whose concerted aberrant activity within tightly regulated modules (tumor checkpoints) is responsible for the mechanistic implementation and maintenance of specific tumor cell states. By leveraging these methodologies, we have developed OncoTreat, a NY CLIA-certified test that leverages large-scale drug-perturbation assays to systematically identify drugs and drug combinations whose mechanism of action is specifically effective in abrogating tumor checkpoint activity, on an individual patient basis. These tests have shown 60% validation rate across 39 predicted drugs that were validated in PDX models from patients who had failed multiple standard-of-care therapies. In this talk, we will introduce these concepts and then demonstrate their application to elucidating drugs capable of targeting transcriptionally distinct tumor niches by single-cell analysis (N-of-1-of-1 studies). In particular, we will show identification and validation, in vivo, of drugs targeting the stemlike progenitor niche of breast adenocarcinomas and the four transcriptionally distinct single-cell subtypes identified in glioblastoma patients. Citation Format: Andrea Califano. Elucidating and targeting mechanisms of single-cell state maintenance: From N-of-1 to N-of-1-of-1 studies [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA21.
Health Effects of Trimellitic Anhydride Occupational Exposure: Insights from Animal Models and Immunosurveillance Programs

Acid anhydrides are used by chemical industries as plasticizers. Trimellitic acid (TMA) is an acid anhydride widely utilized in factories to produce paints, varnishes, and plastics. In addition to causing direct irritant effects, TMA can augment antibody responses in exposed factory workers leading to occupational asthma. Therefore, industries producing TMA have implemented occupational immunosurveillance programs (OISPs) to ensure early diagnosis and medical management, involving exposure reduction/ complete removal of sensitized workers from exposure areas. Multiple animal models (mice strains, rat stains, guinea pig, swine) with different exposure patterns (dermal, nasal, vapor inhalation exposures for different time frames) have been described to elucidate the pathophysiology of TMA exposure. In TMA factories, in spite of implementing advanced environmental controls and personal protective measures to limit exposure, workers become TMA-sensitized. Animal models revealed sIgG, sIgE, sIgA, and sIgM along with pulmonary lesions, cellular infiltrates, alveolar hemorrhage, and pneumonitis associated with TMA exposure. Molecular studies showed involvement of specific functional gene clusters related to cytokine and chemokine responses, lung remodeling, and arginase function. However, thus far, there is no evidence supporting fetotoxic or carcinogenic effects of TMA. OISP data showed IgG and IgE responses in exposed factory workers. Interestingly, timelines for detectable sIgG response, in conjunction with its magnitude, have been shown to be a predictor for future sIgE response. OISPs have been very successful so far at creating a healthy and safe working environment for TMA-exposed factory workers. Graphical Abstract Trimellitic Acid (TMA), used to produce paints, varnishes and plastics, can cause irritant-mediated and immune-mediated occupational health problems. NCBI pubmed search indicated that multiple animal models (different animal types, with chronic vs. acute exposure type, using TMA dust/suspension applied via dermal or other routes) have been used by investigators to elucidate the pathobiology of TMA-exposure. Several outcomes have been measured including humoral, lung/ airway, lymph nodes and dermal/ ear thickening responses. Studies on human subjects have been conducted mostly as parts of Occupational immunosurveillance programs (OISPs) implemented to identify TMA-sensitized workers (using ImmunoCAP and Skin prick testing), monitoring them longitudinally and their medical management including exposure reduction/ complete removal of sensitized workers from exposure areas. Clinical management also includes identification of irritant-induced and/ or immune-mediated outcomes of TMA occupational exposure. Collectively, these studies have led to important insights into the pathomechanism of TMA-exposure and have been very successful at creating a safe working environment for TMA-exposed factory workers.
Structure, Morphology, and Rheology of Polyelectrolyte Complex Hydrogels Formed by Self-Assembly of Oppositely Charged Triblock Polyelectrolytes

We present scattering and rheology studies on model polyelectrolyte complex (PEC) hydrogels that form upon self-assembly of symmetric oppositely charged triblock polyelectrolytes in aqueous media. The hydrogel assembly is driven by associative phase separation of charged end-blocks to form PECs while the neutral mid-blocks restrict bulk phase separation of the PECs, leading to three-dimensional networks with PEC domains surrounded by neutral polymer coronae at sufficiently high polymer concentrations. Comprehensive characterization of the hydrogel structure (PEC domain size, morphology, spacing, and ordering) was enabled by a series of triblock polyelectrolytes with independently varying block lengths, facilitating the construction of morphology maps that offered direct comparisons with earlier theoretical predictions and highlighted the contributions of the charged and neutral blocks in directing PEC morphologies and hydrogel microstructures. Comparisons between the microstructure and shear rheology response emphasize the interplay between PEC domain morphologies and hydrogel flow behaviors. Furthermore, by drawing parallels with rheological models for associating polymer networks, we present preliminary insights into the role of chain-exchange dynamics between the PEC domains and cooperative electrostatic interactions in influencing the hydrogel flow properties.
High-resolution acoustic localization of changes in spatially-distributed coherent sources for structural health monitoring

Localization of acoustic sources is a common remote sensing goal. When multiple sources are present and coherent, high-resolution localization typically becomes more challenging. The spectral estimation method with additive noise (SEMWAN) is an existing technique for high-resolution localization of incoherent monopole sources in low-signal-to-noise environments. SEMWAN utilizes a reference measurement to incoherently suppress background noise, but its performance suffers in applications involving spatially-distributed coherent sources, such as like a vibrating plate. However, by subtracting a reference measurement and using subarray averaging, SEMWAN can be extended to localization of small changes in distributed coherent sources. This revised approach, the spectral estimation method with coherent background removal (SEMCBR), permits remote acoustic localization of damage in a vibrating structure. A simple multi-source experiment using an 8-by-8 planar square microphone array with 6-cm spacing in both horizontal directions was performed to validate SEMCBR at a frequency of 5.0 kHz. Additional SEMCBR experimental results are reported for the same array placed 1.0 m above a 30 cm × 30 cm vibrating plate with and without damage. Cuts, boundary failures and delamination of a composite plate were successfully located with conventional spherical-wave beamforming and SEMCBR using a 0.1 to 6.0 kHz bandwidth. However, SEMCBR provides 4 to 6 times better resolution.
The Zombie Virus Pandemic: An Innovative Simulation Integrating Virology, Population Health, and Bioethics for Preclinical Medical Students

Introduction Understanding population health in the context of infectious disease outbreaks is an important physician competency. However, identifying effective ways to engage early medical student...
THE FUNDAMENTAL MULTI-BASELINE MODE-MIXING FOREGROUND IN 21 cm EPOCH OF REIONIZATION OBSERVATIONS

The primary challenge for experiments measuring the neutral hydrogen power spectrum from the epoch of reionization (EoR) is mode-mixing effects, where foregrounds from very bright astrophysical sources interact with the instrument to contaminate the EoR signal. In this paper, we identify a new type of mode mixing that occurs when measurements from non-identical baselines are combined for increased power spectrum sensitivity. This multi-baseline effect dominates the mode-mixing power in our simulations and can contaminate the EoR window, an area in Fourier space previously identified to be relatively free of foreground power.
Machine Learning-Based Classification of Lignocellulosic Biomass from Pyrolysis-Molecular Beam Mass Spectrometry Data.

High-throughput analysis of biomass is necessary to ensure consistent and uniform feedstocks for agricultural and bioenergy applications and is needed to inform genomics and systems biology models. Pyrolysis followed by mass spectrometry such as molecular beam mass spectrometry (py-MBMS) analyses are becoming increasingly popular for the rapid analysis of biomass cell wall composition and typically require the use of different data analysis tools depending on the need and application. Here, the authors report the py-MBMS analysis of several types of lignocellulosic biomass to gain an understanding of spectral patterns and variation with associated biomass composition and use machine learning approaches to classify, differentiate, and predict biomass types on the basis of py-MBMS spectra. Py-MBMS spectra were also corrected for instrumental variance using generalized linear modeling (GLM) based on the use of select ions relative abundances as spike-in controls. Machine learning classification algorithms e.g., random forest, k-nearest neighbor, decision tree, Gaussian Naive Bayes, gradient boosting, and multilayer perceptron classifiers were used. The k-nearest neighbors (k-NN) classifier generally performed the best for classifications using raw spectral data, and the decision tree classifier performed the worst. After normalization of spectra to account for instrumental variance, all the classifiers had comparable and generally acceptable performance for predicting the biomass types, although the k-NN and decision tree classifiers were not as accurate for prediction of specific sample types. Gaussian Naive Bayes (GNB) and extreme gradient boosting (XGB) classifiers performed better than the k-NN and the decision tree classifiers for the prediction of biomass mixtures. The data analysis workflow reported here could be applied and extended for comparison of biomass samples of varying types, species, phenotypes, and/or genotypes or subjected to different treatments, environments, etc. to further elucidate the sources of spectral variance, patterns, and to infer compositional information based on spectral analysis, particularly for analysis of data without a priori knowledge of the feedstock composition or identity.
Investigating the Impact of Task Significance on Task Engagement and Enjoyment in Digital Games

The Positive Psychologists Peterson, Park, and Seligman identified three paths to human happiness, which they called orientations to happiness: pleasure, flow and meaning. Pleasure can be attained by making games beautiful and pleasurable to the five senses, and flow can be attained with dynamic difficulty adjustment to maintain an optimal level of challenge. However, to the best of our knowledge there has yet to be empirical research showing the impact of meaning on enjoyment in digital games. This study aims to fill that gap in the literature. An online controlled experiment with 440 total participants is proposed to test the impact of Task Significance on Task Engagement and Enjoyment. Participants will play one of 12 versions of a custom research game online (3 × 4 factorial experimental design), and then complete an online survey. Two different ways to facilitate Task Significance in games are proposed and tested: narrative framing and character upgrading mechanisms. This results of this experiment will advance the study of game enjoyment by testing how well these two ways of designing for meaning or Task Significance lead to enjoyment in digital games.
The Role of Stable Security in Resettled Refugees’ Sense of Wellbeing

We examine resettled refugees’ construction of wellbeing using semi-structured interviews of Somali, Hmong, and Middle Eastern refugees in the United States and Canada. Resettled refugees’ descript...
MDS-426: Cardiovascular Disease and Marrow Vascular Markers in Patients with Myeloid Malignancies

Context: The incidence of both myeloid malignancies and cardiovascular disease (CVD) increases with age. We aimed to study whether the presence of CVD is associated with worse outcomes in patients with myeloid malignancies and to delineate a possible mechanism. Objective: Compare overall survival (OS) and marrow vascular density among patients with and without CVD. Design: We retrospectively reviewed 295 previously untreated patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasm (MDS/MPN). CVD included congestive heart failure, coronary artery disease, arrhythmia, peripheral vascular disease, congenital heart disease, and/or cerebrovascular accident. CVD and no-CVD patient characteristics were compared using Fisher’s exact and t-tests. OS was estimated by Kaplan-Meier analysis. Microvascular density (MVD) was determined in CD34-stained bone marrow sections of 20 MDS patients (11 with and 9 without CVD). The mean number of blood vessels was calculated for each sample and compared using the t-test. Setting: University of Maryland Greenebaum Comprehensive Cancer Center, in Baltimore, Maryland. Patients: The study included 228 (77%) patients with AML and 67 (23%) with MDS or MDS/MPN, of whom 92 had CVD (31%) and 203 (69%) did not. Median age at diagnosis was 66 years (range 19–89). Results: For AML patients, 1-, 2- and 3-year OS in CVD vs no-CVD groups was 46% vs 70%, 34% vs 53%, and 26% vs 43%, respectively [HR 1.9, 95% CI = 1.35, 2.67]. For MDS patients, 44% vs 81%, 26% vs 51%, and 26% vs 49% [HR 2.52, 95% CI = 1.27, 5]. In a multivariable regression model accounting for age, performance status, and karyotype, CVD independently predicted worse OS. We hypothesized that treatment response might be affected by MVD, but we did not find a significant difference in MVD in patients with CVD vs no-CVD (mean score 17 vs 22, p=0.4), ever smoker vs never smoker (mean score 19 vs 20, p=0.9), or with vs without diabetes mellitus (mean score 23 vs 13, p=0.1), although the lack of significant difference may be attributed to the small sample size. Conclusions: CVD is a predictor of survival outcomes in patients with AML and MDS. Variability in MVD is a possible mechanism of impaired treatment response in CVD patients, which warrants further evaluation.
Predicting Progression of Alzheimer’s Disease With Magnetic Resonance

Advances in the field of molecular biology concerning Alzheimer’s disease (AD) generate the possibility of useful therapeutic interventions in the near future. The major beneficiaries of disease-modifying treatments that are currently under development will be those patients who have early pathological involvement. Improved methods for early diagnosis and noninvasive surrogates of disease severity in AD are crucial for early therapeutic interventions and for measuring their effectiveness. Various quantitative magnetic resonance (MR) techniques that measure the anatomic, biochemical, microstructural, functional, and bloodflow changes are being evaluated as possible surrogate measures of disease progression. Cross-sectional and longitudinal studies indicate that MR-based volume measurements are potential surrogates of disease progression in AD, starting from the preclinical stages. The recent development of amyloid imaging tracers for positron emission tomography has been a major breakthrough in the field of imaging markers for AD. Efforts to image plaques also are underway in MRI. As with indirect MR measures, the approaches that directly image the pathological substrate will need to undergo a validation process by longitudinal studies to prove their usefulness as predictors of AD.
On Optimal Solutions of Answer Set Optimization Problems

In 2003, Brewka, Niemela and Truszczynski introduced answer-set optimization problems. They consist of two components: a logic program and a set of preference rules. Answer sets of the program represent possible outcomes; preferences determine a preorder on them. Of interest are answer sets of the program that are optimal with respect to the preferences. In this work, we consider computational problems concerning optimal answer sets. We implement and study several methods for the problems of computing an optimal answer set; computing another one, once the first one is found; and computing an optimal answer set that is similar to respectively, dissimilar from a given interpretation. For the problems of the existence of similar and dissimilar optimal answer set we establish their computational complexity.