cssi/SciSciGPT-SciSciNet huggingface dataset:
Joint Analysis of Multiple Traits in Rare Variant Association Studies

The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, the majority of existing methods for the joint analysis of multiple traits test association between one common variant and multiple traits. However, the variant-by-variant methods for common variant association studies may not be optimal for rare variant association studies due to the allelic heterogeneity as well as the extreme rarity of individual variants. Current statistical methods for rare variant association studies are for one single trait only. In this paper, we propose an adaptive weighting reverse regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compare the performance of AWRR with canonical correlation analysis (CCA), Single-TOW, and the weighted sum reverse regression (WSRR). Our results show that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most scenarios, AWRR is more powerful than Single-TOW and WSRR.
Abstract 3950: The role of microRNA-130a in regulating HOXA5 expression in breast cancer progression

Introduction: Micro RNAs (miRNAs) are key post -transcriptional and translational regulators of gene expression and regulate diverse physiological activities involving development, cell growth, differentiation, apoptosis, and pathological processes such as heart disease and cancer. In tumorigenesis miRNAs function as oncogenes or tumor suppressors. HOXA5 belongs to the family of homeobox (HOX) genes, which encode a highly conserved family of transcription factors that are known to regulate body patterning during embryogenesis. HOXA5 plays a major role in mesenchymal-epithelial interactions during organogenesis. Sukumar et al have demonstrated that HOXA5 loss of function leads to loss of p53 expression in mammary epithelial cells, which in turn contributes to malignant transformation, which is why understanding the mechanisms by which HOXA5 expression is dysregulated in breast cancer is critical. We identified a consensus binding sequence for miR-130a in the 3′-UTR of the HOXA5 coding region. Previous studies in our laboratory have shown that miR-130a downregulates HOXA5 expression in vascular endothelial cells. In this study we characterize the role of miR130a in downregulating HOXA5 expression that in turn can decrease p53 expression and function in breast cancer cells resulting in tumor proliferation, progression and metastasis. Methods: We determined whether mitogenic factors in serum affect miR130a and HOXA5 mRNA expression in the breast epithelial cell line MCF10A. Correlation between the expression of miR130a and HOXA5 mRNA expression in the MCF-10 breast progression series cell lines that model the progression from normal mammary epithelium (MCF-10A), ductal carcinoma in situ (MCF10.DCIS.com), to fully malignant (MCF10.CA1) was examined. In addition, we silenced miR-130a using a specific 2’-O-methyl-modified inhibitor and determined whether knocking it out increases HOXA5 mRNA expression in MCF10A cells. The expression levels of miR130a and HOXA5 were measured using quantitative reverse transcriptase real time PCR (QRT-PCR). Results: First, we observed that miR130a expression increases by 2.2 fold and HOXA5 mRNA levels decreases by 0.2 fold following treatment with 5% horse serum in MCF10A cells. Next, we noted that miR-130a expression increases and HOXA5 mRNA expression decreases as tumorigenicity increases in MCF10A progression series cell lines. Finally, knocking out miR-130a activity increased HOXA5 mRNA expression in MCF10A cells, demonstrating that HOXA5 is regulated by miR130a in these cells. Conclusion: Overall our results indicate that miR130a regulates HOXA5 in breast cancer cells and thus may have a role in breast tumor progression. This study will enable us to decipher the role of mir130a in breast tumor progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3950. doi:10.1158/1538-7445.AM2011-3950
Effects of Timed Bright-Light Exposure on Shift-Work Adaptation in Middle-Aged Subjects

Shift workers suffer from a constellation of symptoms that can severely compromise their ability to perform optimally on-shift. The largest single factor contributing to shift-worker problems is sleep disturbance, and there is little question that the primary cause of such sleep disturbance is circadian disruption. Recently, a number of studies have demonstrated that timed exposure to bright light can help facilitate adaptation to simulated shift-work schedules, at least in younger subjects. The aim of the current study was to assess the effects of bright-light interventions in middle-aged individuals undergoing a simulated shift-work regimen. Results indicate that although light was effective in resetting the circadian clocks of these subjects by more than 6 hours, there was little effect on measures of on-duty alertness and performance or on off-duty sleep. These findings suggest that middle-aged subjects may be less phase-tolerant than young subjects, and they raise questions concerning the utility of bright-light interventions in some shift-work populations.
A Security Analysis of Two Commercial Browser and Cloud Based Password Managers

In this paper, we analyze the security of two very popular commercial password managers: Last Pass and Robo Form. Both of them are Browser and Cloud based Password Managers (BCPMs), and both of them have millions of active users worldwide. We investigate the security design and implementation of these two BCPMs with the focus on their underlying cryptographic mechanisms. We identify several vulnerabilities that could be exploited by outsider and insider attackers to break the security of these two BCPMs.
Applications of 3D shape analysis and retrieval

With recent advances in 3D modeling and scanning technologies, large number of 3D models are created and stored in different databases. This has created an impetus to develop effective 3D shape analysis and 3D shape retrieval algorithms for these domains. This has made the field of 3D shape analysis and retrieval become an active area of research in the 3D community. In this paper we will survey few applications where 3D shape analysis and retrieval has been applied effectively. The main applications we have discussed are: 3D human shape analysis; CAD/CAM applications; structural bioinformatics; and other applications.
Predicting impact of weather caused blackouts on electricity customers based on risk assessment

This study evaluates the outage probability and electricity customer cost under the potential weather caused power blackouts. Risk assessment of the weather impact on customers is implemented and visualized in ArcGIS map. The methodology correlates the historical large power outage events with the corresponding weather condition of the time, uses weather forecast data to assess the risk for customers, and compares the results in different predicted weather conditions.
Association of posttraumatic stress disorder symptoms with migraine and headache after a natural disaster.

Objective Previous research shows that migraine and general headache symptoms increase after traumatic events. Questions remain about whether posttraumatic stress disorder (PTSD) produces migraine/headache symptoms, or if individuals afflicted by migraine/headache are especially likely to develop PTSD. We test whether PTSD symptoms following a natural disaster are associated with higher odds of reporting frequent headaches/migraines postdisaster. We decompose PTSD into intrusion, avoidance, and hyperarousal symptom clusters to examine which, if any, are uniquely related to headache/migraine postdisaster. Method We use prospectively collected pre- and postdisaster data to explore whether overall PTSD symptoms and symptom clusters are associated with migraine/headache in a sample of Hurricane Katrina survivors. We account for severity of hurricane exposure and control for baseline migraine and headache problems to reduce the probability that heightened PTSD susceptibility among those who already suffered from the conditions could explain observed associations. Results PTSD symptoms were associated with higher odds of experiencing frequent headaches or migraines with a standard deviation change in PTSD score corresponding to over twice the odds (95% confidence interval [1.64, 2.68]) of having trouble with frequent headaches or migraines in the post-Katrina period. Each additional point on the intrusion subscale (sample M [SD] = 1.6 [1.1]) was associated with 55% higher odds of reporting frequent headache/migraine (95% confidence interval [1.03, 2.33]), but we found no association with avoidance or hyperarousal symptoms. Conclusions Clinicians and disaster planners should be aware that disaster survivors might be at heightened risk of migraine/headache episodes, and those experiencing intrusive reminders may be most affected. (PsycINFO Database Record
Knockdown of an ABC transporter leads to bright red eyes in the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae)

Compound eye color is an important biological character of insects, which is determined by the nature of eye pigments. Ommochrome is the solely source of eye color for some insects, while pteridines is also needed for the other insect species. However, little is known about the eye pigment composition for any planthopper. Scarlet is an ABC (ATP-binding cassette) transporter protein, which functions as the transmembrane transporter for ommochrome precursor. The failure of Scarlet function can cause bright red or white eyes in different species, which depending on the nature of eye pigments. Here, we identified a scarlet ortholog gene (Nlst) from the brown planthopper (BPH), Nilaparvata lugens, which is a destructive insect pest of rice. Nlst is the first characterized eye pigment transporter gene from Hemipteran. NlSt, the protein deduced from Nlst, has an open reading frame (ORF) of 629 amino acids with the two sequence logos for eye pigment transporters. Expression profile revealed that Nlst expressed at all development stages and had the highest transcript level in head. Knockdown the Nlst transcript, the wild-type eye color partially changed to bright red, while not to white. Meantime, the ommochrome level in heads reduced to 73.4%. These results suggested that the eye coloration of BPH needs both ommochrome and pteridines pigments. Because nymphal RNAi with Nlst leading to a clearly distinguished phenotype from the control individuals, Nlst maybe a suitable genetic marker to exploit embryonic RNAi technique in this insect pest.
On the structure and dynamics of stratified wakes generated by submerged propagating objects

ABSTRACTThe structure and intensity of the intermediate wake generated by a submerged propagating body in a stratified fluid was studied using a combination of (i) numerical simulations, (ii) field measurements, and (iii) laboratory experiments. The numerical component offered guidance for the field work performed in Monterey Bay (CA, USA) in the summer of 2015. The field work focused on subsurface thermal signatures of a submerged propagating object. Vertical temperature profiles suggested that long-term changes in thermal stratification can occur after the passage of a towed body. Horizontal temperature variability, measured by an autonomous underwater vehicle facilitated the identification of the wake using perturbation temperature variance as the key diagnostic variable. Analogous thermal signatures of stratified wakes were found in ocean observations and in modelling results. The influence of the tow ship on the wake was shown to be minimal. Laboratory experiments focused on the surface expression of...
Moonlighting GAPDH and Ischemia: Cellular and Molecular Effects of Oxygen Deprivation and Reperfusion

Ischemia represents an existential threat not only to organ and cell viability but also to life itself. For that reason, organisms respond with specific changes in cell structure and function, which may be organ specific. These include modulation of GAPDH gene expression, its protein– protein interactions, changes in subcellular localization, and its posttranslational modification. In particular, GAPDH mRNA synthesis is diminished, coordinating with increases in inducible nitric oxide (NO) synthase during neuronal ischemia. GAPDH is required for glutamate excitotoxicity during neuronal ischemia; for poly (ADP) ribose polymerase inhibition of glycolysis during renal ischemia; and NO-induced changes in gene expression and cell function in leucocytes as well as in retinal cells; and, lastly, differential age-related responses to ischemia in skeletal muscle.
Universal Outpour: A Pneumatological Model for Engaging the Arts

The arts can be viewed as an outworking of the Spirit being poured out on all flesh. The universal outpour motif is a root metaphor that is able to situate the arts in a renewal framework that relates both communally to the broader cultural context and within a context of charismatic worship. After assessing various creational and incarnational models, this chapter adopts a pneumatocentric root metaphor to base a pneumatological model robust enough to evaluate the arts in and around the charismatic renewal. Through this model one can look at the way the charismatic renewal has utilized various art forms communally and within the context of worship, allowing us to see how the Spirit is alive and at work in the arts, and how the charismatic renewal gives a unique pneumatological perspective of the arts to the artworld and the broader field of theological aesthetics.
Fracture mechanics model for subthreshold indentation flaws

A fracture mechanics model for subthreshold indentation flaws is. described. The model describes the initiation and extension of a microcrack from a discrete deformation-induced shear “fault” (shear crack) within the contact zone. A stress-intensity factor analysis for the microcrack extension in residual-contact and applied-stress fields is used in conjunction with appropriate fracture conditions, equilibrium in Part I and non-equilibrium in Part II, to determine critical instability configurations. In Part I, the K-field relations are used in conjunction with the Griffith requirements for crack equilibrium in essentially inert environments to determine: (i) the critical indentation size (or load) for spontaneous radial crack pop-in from a critical shear fault under the action of residual stresses alone; (ii) the inert strengths of surfaces with subthreshold or postthreshold flaws. The theory is fitted to literature data for silicate glasses. These fits are used to “calibrate” dimensionless parameters in the fracture mechanics expressions, for later use in Part II. The universality of the analysis in its facility to predict the main features of crack initiation and propagation in residual and applied fields will be demonstrated. Special emphasis is placed on the capacity to account for the significant increase in strength (and associated scatter) observed on passing from the postthreshold to the subthreshold domain.
Ultrahigh-transparency, ultrahigh-haze nanograss glass with fluid-induced switchable haze

Optoelectronic applications such as solar cells and light-emitting diodes would benefit from glass substrates with both high transparency and high haze to improve power conversion and extraction efficiencies, respectively. In this Letter, we demonstrate glass with grass-like nanostructures that displays ultrahigh transparency and ultrahigh haze (both over 95% at wavelength 550 nm). The nanograss is fabricated by a scalable maskless reactive ion etching process in fused silica where the height is controlled via the etch time. We demonstrate that shorter nanograss ( 6 μm height), though the transmission decreases slightly to less than 92%. Finally, we demonstrate that various fluids with a similar index of refraction as the glass may be used to switch the haze of these substrates.
Recent mass spectrometry-based techniques and considerations for disulfide bond characterization in proteins.

Disulfide bonds are important structural moieties of proteins: they ensure proper folding, provide stability, and ensure proper function. With the increasing use of proteins for biotherapeutics, particularly monoclonal antibodies, which are highly disulfide bonded, it is now important to confirm the correct disulfide bond connectivity and to verify the presence, or absence, of disulfide bond variants in the protein therapeutics. These studies help to ensure safety and efficacy. Hence, disulfide bonds are among the critical quality attributes of proteins that have to be monitored closely during the development of biotherapeutics. However, disulfide bond analysis is challenging because of the complexity of the biomolecules. Mass spectrometry (MS) has been the go-to analytical tool for the characterization of such complex biomolecules, and several methods have been reported to meet the challenging task of mapping disulfide bonds in proteins. In this review, we describe the relevant, recent MS-based techniques and provide important considerations needed for efficient disulfide bond analysis in proteins. The review focuses on methods for proper sample preparation, fragmentation techniques for disulfide bond analysis, recent disulfide bond mapping methods based on the fragmentation techniques, and automated algorithms designed for rapid analysis of disulfide bonds from liquid chromatography–MS/MS data. Researchers involved in method development for protein characterization can use the information herein to facilitate development of new MS-based methods for protein disulfide bond analysis. In addition, individuals characterizing biotherapeutics, especially by disulfide bond mapping in antibodies, can use this review to choose the best strategies for disulfide bond assignment of their biologic products.
Somatic Embryogenesis in Tropical Fruit Trees

The production of tropical fruits exceeds that of temperate fruits (8). Tropical fruits are not only important components of the diet in many countries, but their exportation provides a major source of income. This is particularly true of those fruit crops that can be grown on a large-scale plantation basis, e. g., bananas, papayas, etc. Additional export income is generated by the export of crude secondary products that can be recovered from some tropical fruits, e. g., papain from papaya. Thus, in areas of the tropics with few recoverable natural resources, tropical fruit production not only enhances the quality of life, but also provides a valuable and often irreplaceable source of income.
Advanced air traffic automation : A case study in distributed decentralized control

In this survey chapter, we present some of the issues in designing algorithms for the control of distributed, multi-agent systems. The control of such systems is becoming an increasing issue in many areas owing to technological advances which make it possible to take “legacy” systems to new levels of functioning and efficiency. Of specific interest to us in this chapter is advanced air traffic management (ATM) to increase the efficiency and safety of air travel while accommodating the growing demand for air traffic. ATM systems will replace the completely centralized, ground-based air traffic control procedures. Within ATM, the concept of free flight allows each aircraft to plan four dimensional trajectories in real time, thus replacing the rigid and inefficient discrete airspace structure. These changes are feasible due to technological innovations such as advanced flight management systems with GPS. In this chapter, we propose a decentralized ATM architecture, in which some of the current air traffic control functionality is moved on board aircraft. Within this framework, we present the issues in hybrid systems verification and design for safe conflict resolution strategies between aircraft. Both cooperative and noncooperative conflict resolution strategies are presented along with verification methods based on Hamilton-Jacobi theory, automata theory, and the theory of games.
Incentive Compatible Proactive Skill Posting in Referral Networks

Learning to refer in a network of experts (agents) consists of distributed estimation of other experts’ topic-conditioned skills so as to refer problem instances too difficult for the referring agent to solve. This paper focuses on the cold-start case, where experts post a subset of their top skills to connected agents, and as the results show, improve overall network performance and, in particular, early-learning-phase behavior. The method surpasses state-of-the-art, i.e., proactive-DIEL, by proposing a new mechanism to penalize experts who misreport their skills, and extends the technique to other distributed learning algorithms: proactive-\(\epsilon \)-Greedy, and proactive-Q-Learning. Our proposed new technique exhibits stronger discouragement of strategic lying, both in the limit and finite-horizon empirical analysis. The method is shown robust to noisy self-skill estimates and in evolving networks.
Incentives to Take Care Under Contributory and Comparative Fault

Previous literature on contributory versus comparative negligence has shown that they reach equivalent equilibria. These results, however, depend upon a stylized application of the Hand Formula and an insufficiently coarse model of strategic incentives. Taking this into account, we identify a set of cases where care by one agent significantly increases the benefits of care by the other. When such cases obtain under bilateral harm, comparative negligence generates greater incentives for care, but this additional care occurs only when care is not socially optimal. By contrast, under unilateral harm or asymmetric costs of care, contributory negligence creates socially excessive care. Therefore, it is possible to socially rank negligence regimes depending upon the symmetry of potential harm and costs of care. We discuss a potential reform, the Retrospective Negligence Test, that when applied in the case of bilateral harm would make comparative negligence optimal.
HCV treatment barriers among HIV/HCV co-infected patients in the US: a qualitative study to understand low uptake among marginalized populations in the DAA era.

Background Well-tolerated, highly effective HCV treatment, known as direct-acting antivirals (DAAs), is now recommended for all people living with HCV, providing the tools for HCV elimination. We sought to understand treatment barriers among low-income HIV/HCV coinfected patients and providers with the goal of increasing uptake. Methods In 2014, we conducted 26 interviews with HIV/HCV co-infected patients and providers from a San Francisco clinic serving underinsured and publically-insured persons to explore barriers impacting treatment engagement and completion. Interview transcripts were coded, and a thematic analysis was conducted to identify emerging patterns. Results Conditions of poverty-specifically, meeting basic needs for food, shelter, and safety-undermined patient perceptions of self-efficacy to successfully complete HCV treatment programs. While patient participants expressed interest in HCV treatment, the perceived burden of taking daily medications without strong social support was an added challenge. This need for support contradicted provider assumptions that, due to the shorter-course regimens, support is unnecessary in the DAA era. Conclusions Interferon-free treatments alone are not sufficient to overcome social-structural barriers to HCV treatment and care among low-income HIV/HCV co-infected patients. Support for patients with unmet social needs may facilitate treatment initiation and completion, particularly among those in challenging socioeconomic situations.
Autonomic and Redox Imbalance Correlates With T-Lymphocyte Inflammation in a Model of Chronic Social Defeat Stress

Patients diagnosed with post-traumatic stress disorder (PTSD) are at a significantly elevated risk of developing comorbid inflammatory conditions, but the mechanisms underlying this predilection remain unclear. Our previous work has shown that T-lymphocytes exposed to elevated levels of norepinephrine (NE) displayed a pro-inflammatory signature reminiscent of an autoreactive phenotype. With this, we hypothesized that the increased sympathetic tone observed during psychological trauma may be promoting pro-inflammatory T-lymphocytes, which causes a predisposition to comorbid inflammatory conditions. Here, we examined the consequences of psychological trauma on splenic T-lymphocytes using a mouse model of repeated social defeat stress. Social defeat led to anxiety-like and depression-like behavior as has been previously described. The spleens of socially-defeated mice showed significant elevations of NE, tyrosine hydroxylase (TH), and acetylcholinesterase (ACHE) levels, which appeared to be due in part to increased expression within T-lymphocytes. Additionally, T-lymphocytes from stressed animals showed higher levels of pro-inflammatory cytokines and mitochondrial superoxide. Interestingly, in this model system, close associations exist within splenic T-lymphocytes amid the autonomic, inflammatory, and redox environments, but these only weakly correlate with individual behavioral differences among animals suggesting the psychological and physiological manifestations of trauma may not be tightly coupled. Last, we describe, for the first time, elevations in calprotectin levels within T-lymphocytes and in circulation of psychologically stressed animals. Calprotectin correlated with both behavioral and physiological changes after social defeat, suggesting the potential for a new biological marker and/or therapeutic target for psychological trauma and its inflammatory comorbidities.
Gender differences in management of patients undergoing catheter ablation of atrioventricular nodal reentry tachycardia.

BACKGROUND Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common type of supraventricular tachycardia (SVT). Similar to other cardiac tests and interventions, gender bias may influence clinical decision making in providing appropriate care for AVNRT patients. We assessed for gender differences in the diagnosis and management of AVNRT patients who underwent catheter ablation. METHODS Patients who underwent catheter ablation for AVNRT were included. We explored the gender difference on various clinical parameters such as the time from SVT symptoms, SVT diagnosis, and first electrophysiology consult to time of catheter ablation. RESULTS Among 140 patients screened, 116 patients met the inclusion criteria, including 67.2% women. Median time from symptoms onset to SVT diagnosis was 18.5 months (interquartile range [IQR] 4.0-58.5) in women versus 4.0 months (0.75-34.7) in men, P = .005. Once SVT was diagnosed, women took a median of 12.5 months (IQR 3.0-57.0) to proceed with ablation versus 3.0 months (1.0-7.0) for men, P ≤ .001. It took a longer time from the first electrophysiology consultation to ablation: 54.5 days (20.75-144.75) for women versus 20.5 days (6.0-46.25) for men, P = .008. Overall, it took 60.0 months (IQR 12.8-132.0) for women to have an ablation from initial symptoms onset versus 15 months (IQR 4.6-48.0) for men, P = .001. Prior to ablation, women had 3.78 ± 3.79 (mean ± SD) emergency department visits for SVT versus men 1.52 ± 1.72 and women tried 1.28 ± 0.82 medications versus men 0.76 ± 0.68, P < .001 and .001, respectively. CONCLUSIONS This study demonstrates significant and multifactorial gender-related disparities in AVNRT diagnosis and treatment. Larger studies are needed to confirm these results.
Unpacking the heritability of body mass index and other ratios.

Objectives Ratios of weight to height, especially body mass index (BMI = kg/m2 ), are often used in epidemiological and genetic studies of health, but the limitations of quantitative genetic analysis of ratios are not widely known. The heritability of these ratios can be closely approximated from a bivariate quantitative genetic model of weight and height which clarifies how BMI heritabilities change. Methods I explored this bivariate approximation and alternative measures through simulated datasets fit with linear mixed models. Simulated data were based on published heritabilities and other statistics for BMI and related anthropometric dimensions from four human samples. Results Inspection of the bivariate approximation and analysis of simulated data show the heritability of weight/height crucially depends on the phenotypic (rP ) and genetic correlations (rA ) between weight and height. Changes in these correlations can have dramatic effects on the heritability of BMI. For example, when rP ≪ rA heritability of BMI is reduced to 35-50% of its value when the correlations are equal. Discussion Increasing adiposity likely decreases the phenotypic correlations more than the genetic correlation resulting in reduced heritability of the ratio. This contrasts with the commonly reported stability or increase of BMI heritability and implies it may result from increased genetic variance in weight in obesogenic environments. The bivariate model offers other advantages over ratios, including estimating the conditional genetic variance or heritability of weight that is unassociated with height, which may prove useful in quantitative and molecular genetic studies.
THE GORTER-MELLINK CONSTANT ASSOCIATED WITH COUNTERFLOW CONVECTION IN PRESSURIZED SUPERFLUID He II (He4)

The validity of the Gorter - Mellink (GM) transport equation has been verified primarily for saturated liquid He II. At high pressures however, the applicability of the GM - equation for transport prediction is not well established, in particular when the pressure is above 1 bar. For this reason the present investigations have the purpose of determining the influence of the pressure on the GM - constant. The data available, including results obtained in this laboratory, show good support for the GM - equation in pressurized He II within data scatter and thermophysical property uncertainty.
A standardized methodology for longitudinal assessment of corneal endothelial morphometry in eye banked corneas

Eye banked research-grade human donor corneas serve as principal ex vivo source for studying the mechanisms that underlie corneal endothelial cell damage/death and survival. Wide-field specular microscopy can be used for corneal endothelial visualization and allows for indirect assessment of endothelial cell function by analyzing endothelial cell density and morphometric parameters. However, a standardized approach is needed to observe corneal endothelial changes over time. This protocol describes reliable ex vivo methods for consecutive analyses of human donor corneal endothelial cell density and morphometric parameters change using a wide-field dual imaging specular microscope. This protocol involves tissue warming, acquisition and analysis of specular endothelial images, assessment of corneal layers with the new Enhance mode, optical pachymetry measurement, and qualitative image quality grading scales. This quantitative and qualitative evaluation of donor corneas allows for a systematic analysis of endothelial dynamic responses to ex vivo induced stress and can be used as a valuable tool to better elucidate specular findings and mechanisms mediating corneal endothelial cell loss in corneal disease and after transplantation.
Synoptic atmospheric circulation patterns associated with deep persistent slab avalanches in the western United States

Abstract. Deep persistent slab avalanches are capable of destroying infrastructure and are usually unsurvivable for those who are caught. Formation of a snowpack conducive to deep persistent slab avalanches is typically driven by meteorological conditions occurring in the beginning weeks to months of the winter season, and yet the avalanche event may not occur for several weeks to months later. While predicting the exact timing of the release of deep persistent slab avalanches is difficult, onset of avalanche activity is commonly preceded by rapid warming, heavy precipitation, or high winds. This work investigates the synoptic drivers of deep persistent slab avalanches at three sites in the western USA with long records: Bridger Bowl, Montana; Jackson, Wyoming; and Mammoth Mountain, California. We use self-organizing maps to generate 20 synoptic types that summarize 5899 daily 500 mbar geopotential height maps for the winters (November–March) of 1979/80–2017/18. For each of the three locations, we identify major and minor deep persistent slab avalanche seasons and analyze the number of days represented by each synoptic type during the beginning (November–January) of the major and minor seasons. We also examine the number of days assigned to each synoptic type during the 72 h preceding deep persistent slab avalanche activity for both dry and wet slab events. Each of the three sites exhibits a unique distribution of the number of days assigned to each synoptic type during November–January of major and minor seasons and for the 72 h period preceding deep persistent slab avalanche activity. This work identifies the synoptic-scale atmospheric circulation patterns contributing to deep persistent slab instabilities and the patterns that commonly precede deep persistent slab avalanche activity. By identifying these patterns, we provide an improved understanding of deep persistent slab avalanches and an additional tool to anticipate the timing of these difficult-to-predict events.
A Model Partnership: Mentoring Underrepresented Students in Medicine (URiM) in Emergency Medicine

Author(s): Goines, Jae; Iledare, Elizabeth; Ander, Douglas; Wallenstein, Joshua; Anachebe, Ngozi; Elks, Martha; Franks, Nicole; White, Melissa; Shayne, Philip; Henn, Megan; Heron, Sheryl | Abstract: Introduction: Creating a racially and ethnically diverse workforce remains a challenge for medical specialties, including emergency medicine (EM). One area to examine is a partnership between a predominantly white institution (PWI) with a historically black college and university (HBCU) to determine whether this partnership would increase the number of underrepresented in medicine (URiM) in EM who are from a HBCU.Methods: Twenty years ago Emory Department of Emergency Medicine began its collaboration with Morehouse School of Medicine (MSM) to provide guidance to MSM students who were interested in EM. Since its inception, our engagement and intervention has evolved over time to include mentorship and guidance from the EM clerkship director, program director, and key faculty.Results: Since the beginning of the MSM-Emory EM partnership, 115 MSM students have completed an EM clerkship at Emory. Seventy-two of those students (62.6%) have successfully matched into an EM residency program. Of those who matched into EM, 22 (32%) have joined the Emory EM residency program with the remaining 50 students matching at 40 other EM programs across the nation.Conclusion: Based on our experience and outcomes with the Emory-MSM partnership, we are confident that a partnership with an HBCU school without an EM residency should be considered by residency programs to increase the number of URiM students in EM, which could perhaps translate to other specialties.
Evidence of a Role for the Hippocampus in Food-Cue Processing and the Association with Body Weight and Dietary Added Sugar.

Objective The current analysis used functional magnetic resonance imaging (fMRI) to explore a model of energy regulation postulating that the hippocampus integrates interoceptive signals and environmental stimuli to suppress responding to food cues. It was hypothesized that hippocampal activity would increase in response to food cues under postnutritive relative to fasted conditions, given the role of the hippocampus in integrating postnutritive signals with food cues, and that obesity, added sugar intake, or a combination of these factors would alter this response. Methods Data were analyzed on 65 participants (29 males). Participants consumed drinks containing 75 g of glucose or water and underwent an fMRI-based food-cue task. Blood-oxygen-level-dependent (BOLD) fMRI was used to examine hippocampal responses to food and nonfood cues. Results In lean participants, the hippocampal BOLD signal was higher following glucose compared with water, but participants with obesity showed the opposite pattern. BMI interacted with added sugar intake such that BMI was more negatively correlated with hippocampal food-cue reactivity after glucose ingestion in individuals who consumed high levels of added sugar. Hippocampal BOLD was negatively correlated with prospective food intake. Conclusions The findings are consistent with the view that energy regulation involves hippocampal processes in humans and that added sugar and excess weight may impair this function.
Utilizing Pine Needles to Temporally and Spatially Profile Per- and Polyfluoroalkyl Substances

As concerns continue to mount over exposure to per- and polyfluoroalkyl substances (PFAS), novel methods of profiling their presence and modifications are greatly needed as some have known toxic and bioaccumulative characteristics while others have unknown effects. This task however is not simple as over 5000 PFAS of interest have been named by the Environmental Protection Agency and this list continues to grow daily. In this work, we utilized widely available archived and field-sampled pine needles and a novel non-targeted analytical method to evaluate the temporal and spatial presence of numerous PFAS. Over 70 PFAS were detected in the pine needles from this study, providing information from the last six decades related to PFAS exposure, contamination, and reduction.
Abstract PO-084: The role of p53 in the development of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a very deadly cancer, with a 5-year survival rate of only 9%. This high mortality rate can be attributed to the lack of early detection methods and to tumors being resistant to treatment, in part due to a highly immunosuppressive tumor microenvironment (TME). The most commonly mutated genes in PDAC include activating mutations in KRAS in >90% of cases and mutations in the tumor suppressor TP53 gene in ~72% of cases. However, how p53, which is a transcription factor, normally suppresses PDAC progression is not well understood. Understanding the pathways through which p53 acts to suppress PDAC will provide key insight into the molecular mechanisms underlying PDAC initiation and progression. Our laboratory has recently shown in genetically engineered mouse models that Kras activation, coupled with p53 inactivation, can drive PDAC from either pancreatic acinar or ductal cells, with acinar cell- and ductal cell-derived tumor signatures resembling the classical and basal-like human PDAC subtypes, respectively. To better understand how p53 loss promotes PDAC, we are focusing on the acinar cell-derived PDAC mouse model and using single-cell transcriptomic technologies to ask in which cell states and through which pathways p53 acts to suppress PDAC development, in particular as PDAC has complex interactions between tumor cells and the TME. In this model, PDAC is driven by oncogenic Kras (KrasG12D) along with either p53 wild type (p53wt) or p53 deficiency (p53flox) in adult acinar cells by a tamoxifen-inducible Ptf1aCreER allele. In the progression of this model, acinar cells can give rise to PDAC likely through a transdifferentiation process called acinar-to-ductal metaplasia (ADM), which leads to pancreatic intraepithelial neoplasias (PanINs) and then PDAC. The initial cell fate transition, ADM, can be activated by growth factors, inflammation, and injury. We have conducted single cell RNA-sequencing (scRNA-seq) to compare early stages of tumor development in the presence and absence of p53. We have also conducted spatial transcriptomic analysis of these samples. Using these combined approaches, we are analyzing tumor cell populations and cells of the tumor microenvironment in the p53wt and p53flox genotypes and have found. We will present our latest single cell analyses on p53 dependent cell states and functional pathways during PDAC development. Understanding how tumor cell states and cells of the tumor microenvironment change with p53 status will reveal different paths of PDAC evolution and uncover novel approaches to improve clinical intervention for human PDAC. Citation Format: Kathryn J. Hanson, Brittany M. Flowers, Nicholas Hughes, Hannes Vogel, Le Cong, Laura D. Attardi. The role of p53 in the development of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-084.
Chapter 4 A Novel Method for Cutting Giant Cells to Study Viral Synthesis in Anucleate Cytoplasm

Publisher Summary The continuous development of new and exacting methods to probe the nature of regulatory mechanisms in the mammalian cell provides the investigator with an ever increasing range of sophisticated tools; still, the extent to which the programming of biochemical events in the nucleus and cytoplasm is interrelated persists as a problem of fundamental concern to the cell biologist. Within the time-space confines of the individual cell, biochemical events have been resolved or dissected by numerous ingenious means. Questions involving the biochemical autonomy of the major portions of the cell, nucleus, and cytoplasm are perhaps answered most directly by the last named technique, where the dissection of individual cells into nucleate and anucleate cytoplasm provides a straight forward means of separating biochemical reactions requiring nuclear participation from those that do not. In spite of the directness of the micrurgical approach, it is used with great hesitancy by most investigators because of the elaborate specialized equipment and technical dexterity required to tool for and perform the simplest of operations. For these reasons, it sought to simplify the micrurgical procedures, first, by working with significantly larger cells than normally available and, second, by modifying the cutting technique to the extent that greater amounts of nucleate and anucleate cytoplasm could be produced, under conditions where they may be manipulated readily for biochemical or virological studies.
Die Grenzen im Kopf: Imagining walls, borders, frontiers, and national identity in Alsace/Elsaß

Political geographers draw distinctions in English between borders, usually conceived of as lines on a map, and frontiers, which are seen as zones. In German, Grenze, a word borrowed from Slavic, and reflecting ethnic differences is often used for both. In French frontiere with its roots in medieval warfare, covers both concepts. Beginning with some considerations of Alsace/Elsas as a frontier zone between Germany and France, this paper will review ongoing debates among historians of nationalism on the definitions of nations, states, and frontiers. It will then trace the historical development in Europe of these concepts from antiquity into the early modern period. It was during the dynastic power struggles of the sixteenth and seventeenth centuries that the concepts of nation and state took on fundamental political significance as rulers made claims to sovereignty in the name of historical nations and borders became enshrined in “international” law as the result of the peace treaties signed in Westphalia in 1648. The essay questions both the historical depth of nations, states, and borders and the teleological assumption of their inevitability and permanence in human political relations. Nations, states, and borders are mental constructs. They were imagined and can be reimagined. A close examination of Alsatian history shows the bloody historical effects of applying these concepts arbitrarily in a cultural borderland and the potential for a different political future for Europe by reimagining borders.
News, Corporate Network and Price Discovery

This paper evaluates the role of a corporate network in spreading news and in particular shows how it affects prices. We build daily corporate news network using companies of the STOXX 50 index as nodes; the weights of the edges are the number of news items sharing common topics between companies. The STOXX 50 includes the top 50 European companies by level of capitalization. We conducted a longitudinal network analysis using the stochastic actor oriented model with daily prices and news for March 2009. We found that there was a 0.55 correlation between the rate of change of the news network and the STOXX 50 index. Even though, the network dynamic by itself cannot fully explain price movements, it can play an important role as part of a predictive model.
The Public Interest in Cultural Property

Public questions affecting cultural property frequently arise: Should an old building be preserved? (Many are, pursuant to "historic preservation" laws.) Should the Crown of St. Stephen be returned to Hungary? (We did return it, over the protests of Hungarian emigres and a number of prominent public figures, including Senator Robert Dole.) Should the United States become a party to the 1970 UNESCO Convention' or the
Explaining Underperformance: Military Propaganda, Theories of Influence, and the Marketing Analogy

One striking pattern in modern counterinsurgency is the late war, military enthusiasm for information operations. The failure of early war strategies based on the provision of violence or protection often stimulates interest in the use of psychological instruments to influence individual and collective political behavior across multiple audiences. According to their proponents, information operations are neglected tools. The application of additional attention and resources, so the argument goes, will deliver results in what are described as “political wars.” The manipulation of communications, they argue, will succeed where the management of violence has failed.
Comparison of computer predictions and magnetic field measurements for an iron spectrometer magnet

Three dimensional computer calculations using the Program TOSCA have been made for a complex-shaped iron magnet. Precision field measurements were made on this magnet in preparation for its installation in a new Low Energy Separated Beam for the post-Booster high proton intensity AGS at Brookhaven National Laboratory. Point-by-point direct comparisons for field values will be described encompassing the entire useful acceptance. The predictability of higher order multipoles will be described, including the region of the magnet ends. Computer predicted focal properties will be compared with results of experimental data analysis. The method of measurement and analysis, as well as comments on the computer calculations will be described. Conclusions will be drawn on the accuracy of calculations with respect to higher order moments and the impact on future beam optical design and execution of three dimensional computer codes. >