cssi/SciSciGPT-SciSciNet huggingface dataset:
Aging of modulation of heart rate

We postulated that measurements of autonomically mediated fluctuations in heart rate might provide a quantitative probe of biological aging. We used power spectrum analysis of instantaneous heart rate while 33 male subjects matched their breathing to a metronome at 15 breaths/min. Measurements were made in supine and standing position. Total power and its two major components, high- and low-frequency power, declined with age in both positions but at different rates. High-frequency power that represents parasympathetically mediated respiratory sinus arrhythmia declined linearly in supine position only in subjects 9-28 yr with a slope of -0.796, which was significantly different from zero at P = 0.0007. The absolute value of high-frequency power in standing position was approximately 60% of that in supine, a difference that was statistically significant (P = 0.01). Low-frequency power that represents beta-adrenergically mediated heart rate fluctuations, especially in standing position, declined linearly to 62 yr of age (P = 0.0001). Mean heart rate increased 17.2 beats/min, and diastolic blood pressure increased 8 mmHg in the entire group in the standing compared with supine position. There were no significant differences in these changes above and below 30 yr of age. We conclude that the influence of the two major mechanisms that modulate heart rate decline at significantly different rates with aging.
Postoperative Atrial Fibrillation Predicts Long-Term Cardiovascular Events after Radical Cystectomy.

Purpose: Postoperative atrial fibrillation after radical cystectomy occurs in 2% to 8% of cases. Recent evidence suggests that transient postoperative atrial fibrillation leads to future cardiovascular events. The long-term cardiovascular implications of postoperative atrial fibrillation in patients undergoing radical cystectomy are largely unknown.Materials and Methods: The Healthcare Cost and Utilization Project State Inpatient Databases for California and Florida were used to identify patients who underwent radical cystectomy between 2007 and 2010. After excluding patients with a history of atrial fibrillation, coronary artery disease and/or stroke, patients were matched using propensity scoring on age, race, insurance status and preexisting comorbidities. Adjusted Kaplan-Meier time-to-event analysis and Cox proportional hazards models were used to assess the effect of postoperative atrial fibrillation on cardiovascular events (acute myocardial infarction and stroke) during postoperative year 1.Results...
Digitizer auditory graph: making graphs accessible to the visually impaired

This paper describes the design goal, design approach, and user testing of an assistive technology called Digitizer Auditory Graphfia sonification software tool that allows users to upload or take an image of a line graph with an optical input device (e.g., webcam, digital camera, cell phone camera) and then hear an auditory graph of the digitized graph image. This technique enables visually impaired students to have a multimodal display of the information in a graph. Preliminary evaluation results indicate that both visually impaired and sighted people can understand the patterns of graphs by listening to auditory graph, and optical input allows them to have simple and fast output results.
Highly degenerate harmonic mean curvature flow

We study the evolution of a weakly convex surface \({\Sigma_0}\) in \({\mathbb {R}^3}\) with flat sides by the Harmonic Mean Curvature flow. We establish the short time existence as well as the optimal regularity of the surface and we show that the boundaries of the flat sides evolve by the curve shortening flow. It follows from our results that a weakly convex surface with flat sides of class Ck,γ, for some \({k\in \mathbb{N}}\) and 0 0 does not depend on the regularity of the initial data.
A simplified distilling head for the measurement of corticosteroids by the formaldehydogenic method.

The measurement of urinary corticosteroids by the formaldehydogenic method of Daughaday, Jaffe and Williams (1) has gained wide acceptance in the routine assessment of adrenocortical function. The distillation of the formaldehyde formed by the periodic-acid oxidation of the steroids bearing a C-21 primary alcohol group is a time-consuming step and, in addition, requires expensive equipment. According to this technique, the solution containing the formaldehyde is transferred to a three-piece distilling apparatus and, after the distillation is completed, the three pieces must be disassembled, thoroughly cleaned, reassembled and the next sample introduced. If two units are run simultaneously, one technician can distill 6 samples in one hour. In our laboratory, approximately 84 per cent of the formaldehyde can be recovered.
Influence of a rural environment on patient access and outcomes for bariatric surgery

Abstract Background Despite a higher rate of obesity in rural populations, there is a 23% decrease in performed bariatric procedures. The influence of a rural environment on surgical outcomes and treatment efficacy is unknown. Methods We retrospectively reviewed all bariatric surgeries performed in a large university hospital in West Virginia from September 2012 to September 2014. Patients were categorized based on their rural–urban commuting area codes. Subject demographic characteristics, insurance provider, type of surgery, completion of program, preoperative body mass index (BMI), percent excess weight loss (%EWL), and percent total weight loss (%TWL) at 6 and 12 months postoperatively, and follow-up appointment attendance were collected. Logistic and linear regression analyses were conducted. Results A total of 122 patients were evaluated with 82 receiving surgery. Of these patients, 77 had Roux-en-Y gastric bypass, and 5 had Sleeve Gastrectomy. Nine patients out of 82 were lost to follow-up at 6 months (n = 73), and 12 patients out of 62 were lost to follow-up at 12 months (n = 50). Rural patients were .283 times less likely to receive bariatric surgery, ( P = .004). However, this relationship was confounded by insurance provider; after controlling for this variable, the relationship between rural status and surgery completion was nonsignificant ( P = .066). Rural status did not predict change in BMI, %EWL, or %TWL at 6 months ( P = .738; P = .848; P = .334) or 12 months ( P = .902; P = .143; P = .195), or compliance for follow-up appointments ( P = .232). Conclusions Rural bariatric patients seem to have decreased success at completing bariatric programs, which is likely confounded by insurance type. Yet, when the rural patient is able to realize the benefits of bariatric surgery, their outcomes are unchanged compared with urban patients. Although the study is limited by sample size, it highlights the need for reducing obstacles for bariatric surgery in an already underserved population, the rural community.
Annotation Trees: LDC's customizable, extensible, scalable, annotation infrastructure

In recent months, LDC has developed a web-based annotation infrastructure centered around a tree model of annotations and a Ruby on Rails application called the LDC User Interface (LUI). The effort aims to centralize all annotation into this single platform, which means annotation is always available remotely, with no more software required than a web browser. While the design is monolithic in the sense of handling any number of annotation projects, it is also scalable, as it is distributed over many physical and virtual machines. Furthermore, minimizing customization was a core design principle, and new functionality can be plugged in without writing a full application. The creation and customization of GUIs is itself done through the web interface, without writing code, with the aim of eventually allowing project managers to create a new task without developer intervention. Many of the desirable features follow from the model of annotations as trees, and the operationalization of annotation as tree modification.
Where’s the Stake? - U.S. Interests in the South China Sea

In recent years, international observers have highlighted the interplay between the United States and China about the South China Sea situation, including statements made by senior diplomats from the two nations at the Association of Southeast Asian Nation (ASEAN) Regional Forum (ARF) meeting in Hanoi, Vietnam, during July of 2010. At that meeting, U.S. Secretary of State Hillary Clinton made remarks about U.S. policy on the South China Sea situation. Days thereafter, China’s Ministry of Foreign Affairs (MOFA) released a statement about the matter, alleging that Secretary Clinton had 'played up' the issue and that her remarks 'were designed to give the international community a wrong impression that the situation in the South China Sea is a cause for grave concern.' The MOFA statement then recounted how China’s Foreign Minister Yang Jiechi 'made an intervention' at the ARF meeting by 'raising a row of questions.' Foreign Minister Yang’s 'row of questions' at the 2010 ARF meeting indicated that China doubts either that the United States has interests in the South China Sea, that those U.S. interests are at risk, or all of the above. This paper will talk about the stakes or interests that a nation holds in a given situation. More specifically, this paper will consider the questions: Does the United States, in fact, have interests in the South China Sea. If so, what exactly are those U.S. interests and what are the elements or components of those interests? And, given the current circumstances of the South China Sea situation, are those U.S. interests truly at risk? The discussion in this paper will be divided into two parts. First, it will identify the interests that the United States holds in the South China Sea. Second, it will provide some personal insights and opinions of the author about two of those interests. This second part will also highlight and examine actions and inactions by other nations in the region that, in the author’s opinion, might be putting those U.S. interests at risk.
Physician Perspectives on Palliative Care for Children With Neuroblastoma: An International Context.

Background Studies have shown that children with cancer globally lack access to palliative care. Little is known regarding physicians’ perceptions of palliative care, treatment access, and self-reported competence in providing palliative care. Procedure Members of the Global Neuroblastoma Network (online tumor board) were surveyed. Eighty-three respondents met inclusion criteria; 53 (64%) completed the survey. Results Most respondents trained in high-income countries (HIC) but practice in low- and middle-income countries (LMIC), and care for more than five patients with neuroblastoma annually. WHO Essential Medicines in palliative care varied in availability, with incomplete access across LMIC centers. Nonpharmacologic therapies were inconsistently available. Contrary to international definitions, 17% of respondents inappropriately considered palliative care as that initiated only after curative therapy is stopped. Mean physician competence composite score (Likert scale 1–5, 5 = very competent) in providing symptomatic relief and palliative care across phases of care was 2.93 (95% CI 2.71–3.22). Physicians reported significantly greater competence in symptom management during cure-directed therapy than during end-of-life (P = 0.02) or when patients are actively dying (P = 0.007). Practicing in HIC, prior palliative care training, having access to radiotherapy, and not having to turn patients away due to bed shortages were significantly predictive of perceived competence in providing palliative care at end of life. Conclusions An international sample identified gaps in treatment and palliative care service availability, in understanding the definition of palliative care, and in self-reported competence in providing palliative care. Increased perceived competence was associated with training, which supports the need for increased palliative care education and advocacy, especially in LMIC.
The Mysterious Ethics of High-Frequency Trading

The ethics of high frequency trading are obscure, due in part to the complexity of the practice. This article contributes to the existing literature of ethics in financial markets by examining a recent trend in regulation in high frequency trading, the prohibition of deception. We argue that in the financial markets almost any regulation, other than the most basic, tends to create a moral hazard and increase information asymmetry. Since the market’s job is, at least in part, price discovery, we argue that simplicity of regulation and restraint in regulation are virtues to a greater extent than in other areas of finance. This article proposes criteria for determining which high-frequency trading strategies should be regulated.
Study on improvement of rice wine quality and flavor by modern biotechnology and separation technique

Based on traditional technology of rice wine production,a new technology of decreasing the alcohol content in rice wine was developed in this paper including immobilization technology,low temperature evaporation,freezing,membrane filtration and separation technology.By applying these techniques,the quality of rice wine was greatly improved and the product was characterized by representative style of yellow color,clear and fragrance.
How Do Preservice Teachers Understand the Use of Research to Inform Practice? Foundational Knowledge for Bridging the Gap

ABSTRACTDespite widespread discourse about the need for teachers to utilize education research, little is known about how teachers learn to engage in this practice. How do preservice teachers understand the use of research to inform their teaching? Set within the context of a mathematics methods course, this study provides a detailed analysis of the written research implementation plans of 29 preservice teachers. The data were analyzed using the principles of grounded theory, and four themes were developed regarding preservice teacher ability to understand research, create an implementation plan, modify the plan, and evaluate the plan. The findings problematize the complex process of research implementation and indicate microskills that teacher educators can address when preparing novices to engage in the process of research utilization.
Introduction: Untimely Ancestors

Sorensen shows that Zora Neale Hurston, Younghill Kang, D’Arcy McNickle, and Americo Paredes participate in a distinct mode of modernism that critiques the constrained position of ethnic subjects within modernity. Furthermore, he demonstrates that these authors share a central concern with contemporary practices of critical multiculturalism. This genealogy has gone unrecognized because current practices of literary recovery tend to pass over the profound negativity of these works in order to produce a celebratory model of literary history in which the injustices of the past are undone in the present. The chapter elaborates an alternative mode of literary history that emphasizes the untimely aspects of recovery movements and provides a more dynamic account of the participation of ethnic writers in literary modernism.
Abstract 2438: Genome-wide screen reveals a role for glucocorticoids in B cell development that can be exploited to improve treatment of B cell acute lymphoblastic leukemia

Glucocorticoids (GCs) are a component of highly effective therapy for B cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer. Although successful in 90% of patients, the prognosis for the remaining 10% is dismal. Because sensitivity to GCs alone predicts outcome well, we hypothesized that enhancing or restoring GC sensitivity can improve outcome. To first determine how GCs kill B-ALL cells, we first measured the transcriptional response of sensitive B-ALL samples to dexamethasone (dex). In addition to apoptotic genes (BIM, BCL2), and metabolic genes (TXNIP) identified in other studies that contribute to cell death, we also found broad regulation of B cell development genes, including key checkpoints (ITGA4, IL7R, and BCL6). This suggested that high levels of GCs push arrested B-ALL cells through development, resulting in cell death. To validate these results, and to identify cellular pathways that modulate GC cytotoxicity, we used a next-generation shRNA screen to knock down every protein-coding gene in the genome. The screen identified 265 genes that significantly modulate GC sensitivity. In addition to validating the importance lymphoid development genes, the screen revealed which cofactors and chromatin modifiers collaborate with GR to orchestrate cell death gene programs. Further we were able to map critical signaling pathways with high resolution, including the pro-survival B cell receptor pathway. Inhibition of PI3Kδ at the apex of this pathway potentiated the response of GC-regulated genes to dex, and synnergized with dex to induce cell death in even the most refractory B-ALL tissue. These results indicate a previously unrecognized for GCs in B cell development that can be exploited to improve both the potency and treatment of lymhoid disease. Citation Format: Miles Pufall, Karina Kruth, Sarah K. Tasian. Genome-wide screen reveals a role for glucocorticoids in B cell development that can be exploited to improve treatment of B cell acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2438.
Marijuana use among young people in an era of policy change: what does recent evidence tell us?

Recent years have witnessed a remarkable series of changes in the perception and availably of marijuana in the United States (US). Although only one in ten (12%) Americans supported the legalizatio...
Soul-searching on the Internet

"The entire scope of human experience can be viewed as a collective effect resulting from elementary particles dutifully following well-understood equations." Statements like this excite deep-seated passions and tend to bring out strongly polarized views. The Pearly Gates of Cyberspace by Margaret Wertheim is a product of this passionate debate.
Quality and design automation: effectiveness against completeness of search

Automated tools for design can improve productivity in an organisation by accelerating the execution of routine tasks. A more interesting consequence of computer–aided packages is the possibility of enhancing the quality of design: the increased efficiency allows for a systematic search of alternative candidates, from which a superior design may be selected. This paper presents an operational definition of quality based on the relative rank of a design with respect to alternative candidates. The impact of an expanded list of candidates on the ultimate quality is explored through both a theoretical analysis and a simulation case study.
Caffeic acid phenethyl ester (CAPE, a product of propolis) as an inhibitor of human breast cancer growth in a pre-clinical study and its effects on factors involved in cell cycle, angiogenesis, and drug resistance

5710 Our original goal has been to establish whether caffeic acid phenethyl ester (CAPE), a bioactive anti-inflammatory component of the propolis, a product of honeybees, can suppress breast cancer formation using a xenograft nude mouse model. We found that orally administered CAPE inhibits growth of human breast cancer cells in nude mice regardless of whether these cells are estrogen receptor (ER) positive (MCF-7) or negative [MDA-MB-231 (MDA-231)] cells. This finding is additionally important because there are fewer therapies available for ER negative tumors. The suppression of xenograft growth was most effective at very low doses of 50 nmol (14.2 μg) CAPE/mouse/day for MCF-7 and 10 nmol (2.84 μg) for MDA-231 xenografts when mice were provided CAPE-containing diets two days prior to cell inoculation for up to 45-60 days afterwards. Toxicity and Drug Resistance gene microarrays using MCF-7 and MDA-231 cells showed that CAPE causes strong down-regulation of anti-apoptotic and cell proliferation genes, as well as of NF-κB transcription factors. Notably, multi-drug resistance 1 (mdr-1) gene was decreased in MDA-231 cells about 4-fold by CAPE, which strongly suggests that CAPE could be useful as an adjuvant to therapeutic drugs, such as paclitaxel (Taxol), which are expelled from tumor cells by mdr-1 protein products. Our preliminary results show that treatment of MDA-231 cells with low doses of CAPE (0.5-20 μM) followed 15 min later with Taxol (1-5 nM) show a dose-dependent decrease in cell viability, with optimal conditions being 1 nM Taxol and 1-5 μM CAPE. Since growth of tumors in vivo requires neovascularization, we also looked for the effects of CAPE on the formation of VEGF, an angiogenic factor, in cultured cells. CAPE had no effect on low VEGF (vascular endothelial growth factor) produced by MCF-7 cells, but dose-dependently inhibited VEGF formation by MDA-231 cells. We also found that a low CAPE dose inhibits formation of capillary-like tubes by endothelial cells. These results suggest that CAPE should inhibit angiogenesis also in mice growing human breast cancer xenografts. We also found that CAPE dose-dependently inhibits viability of both types of cells by enhancing formation of p21 and p27 cell cycle inhibitory proteins and increasing apoptosis. In conclusion, CAPE seems to be very promising as an anti-breast cancer agent because of its anti-proliferative and pro-apoptotic effects, as well as inhibiting angiogenesis. Notably, CAPE also decreases heat shock protein genes as well as mdr-1 and its protein products responsible for drug resistance, thus holding a promise for increasing effectiveness of chemotherapeutic drugs and decreasing their side effects. [This work was supported in part by grants from Susan G. Komen for Cure Foundation (BCTR0600476) and NIEHS (ES00260)]
Medical Licensure Questions and Physician Reluctance to Seek Care for Mental Health Conditions

Abstract Objective To determine whether state medical licensure application questions (MLAQs) about mental health are related to physicians' reluctance to seek help for a mental health condition because of concerns about repercussions to their medical licensure. Methods In 2016, we collected initial and renewal medical licensure application forms from 50 states and the District of Columbia. We coded MLAQs related to physicians' mental health as "consistent" if they inquired only about current impairment from a mental health condition or did not ask about mental health conditions. We obtained data on care-seeking attitudes for a mental health problem from a nationally representative convenience sample of 5829 physicians who completed a survey between August 28, 2014, and October 6, 2014. Analyses explored relationships between state of employment, MLAQs, and physicians' reluctance to seek formal medical care for treatment of a mental health condition because of concerns about repercussions to their medical licensure. Results We obtained initial licensure applications from 51 of 51 (100%) and renewal applications from 48 of 51 (94.1%) medical licensing boards. Only one-third of states currently have MLAQs about mental health on their initial and renewal application forms that are considered consistent. Nearly 40% of physicians (2325 of 5829) reported that they would be reluctant to seek formal medical care for treatment of a mental health condition because of concerns about repercussions to their medical licensure. Physicians working in a state in which neither the initial nor the renewal application was consistent were more likely to be reluctant to seek help (odds ratio, 1.21; 95% CI, 1.07-1.37; P =.002 vs both applications consistent). Conclusion Our findings support that MLAQs regarding mental health conditions present a barrier to physicians seeking help.
Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female.

Abstract Orphanin FQ (OFQ/N) and its receptor, opioid receptor-like receptor-1 (ORL-1), are expressed throughout steroid-responsive limbic and hypothalamic circuits that regulate female ovarian hormone feedback and reproductive behavior circuits. The arcuate nucleus of the hypothalamus (ARH) is a brain region that expresses OFQ/N and ORL-1 important for both sexual behavior and modulating estradiol feedback loops. Within the ARH, the activation of the OFQ/N-ORL-1 system facilitates sexual receptivity (lordosis) through the inhibition of β-endorphin neuronal activity. Estradiol initially activates ARH β-endorphin neurons to inhibit lordosis. Simultaneously, estradiol upregulates coexpression of OFQ/N and progesterone receptors and ORL-1 in ARH β-endorphin neurons. Ovarian hormones regulate pre- and postsynaptic coupling of ORL-1 to its G protein-coupled signaling pathways. When the steroid-primed rat is nonreceptive, estradiol acts pre- and postsynaptically to decrease the ability of the OFQ/N-ORL-1 system to inhibit ARH β-endorphin neurotransmission. Conversely, when sexually receptive, ORL-1 signaling is restored to inhibit β-endorphin neurotransmission. Although steroid signaling that facilitates lordosis converges to deactivate ARH β-endorphin neurons, estradiol-only facilitation of lordosis requires the activation of ORL-1, but estradiol + progesterone does not, indicating that multiple circuits mediate ovarian hormone signaling to deactivate ARH β-endorphin neurons. Research on the role of OFQ/N-ORL-1 in ovarian hormone feedback loops is just beginning. In the rat, OFQ/N may act to terminate gonadotropin-releasing hormone and luteinizing hormone release under positive and negative feedbacks. In the ewe, it appears to directly inhibit gonadotropin-releasing hormone release to mediate progesterone-negative feedback. As a whole, the localization and actions of OFQ/N-ORL-1 system indicate that it may mediate the actions of estradiol and progesterone to synchronize reproductive behavior and ovarian hormone feedback loops.
An exploratory study of whether pregnancy outcomes influence maternal self-reported history of child maltreatment

Abstract Childhood maltreatment is common and has been increasingly studied in relation to perinatal outcomes. While retrospective self-report is convenient to use in studies assessing the impact of maltreatment on perinatal outcomes, it may be vulnerable to bias. We assessed bias in reporting of maltreatment with respect to women’s experiences of adverse perinatal outcomes in a cohort of 230 women enrolled in studies of maternal mental illness. Each woman provided a self-reported history of childhood maltreatment via the Childhood Trauma Questionnaire at two time points: 1) the preconception or prenatal period and 2) the postpartum period. While most women’s reports of maltreatment agreed, there was less agreement for physical neglect among women experiencing adverse perinatal outcomes. Further, among women who discrepantly reported maltreatment, those experiencing adverse pregnancy outcomes tended to report physical neglect after delivery but not before, and associations between physical neglect measured after delivery and adverse pregnancy outcomes were larger than associations that assessed physical neglect before delivery. There were larger associations between post-delivery measured maltreatment and perinatal outcomes among women who had not previously been pregnant and in those with higher postpartum depressive symptoms. Although additional larger studies in the general population are necessary to replicate these findings, they suggest retrospective reporting of childhood maltreatment, namely physical neglect, may be prone to systematic differential recall bias with respect to perinatal outcomes. Measures of childhood maltreatment reported before delivery may be needed to validly estimate associations between maternal exposure to childhood physical neglect and perinatal outcomes.
Extant fold-switching proteins are widespread.

A central tenet of biology is that globular proteins have a unique 3D structure under physiological conditions. Recent work has challenged this notion by demonstrating that some proteins switch folds, a process that involves remodeling of secondary structure in response to a few mutations (evolved fold switchers) or cellular stimuli (extant fold switchers). To date, extant fold switchers have been viewed as rare byproducts of evolution, but their frequency has been neither quantified nor estimated. By systematically and exhaustively searching the Protein Data Bank (PDB), we found ∼100 extant fold-switching proteins. Furthermore, we gathered multiple lines of evidence suggesting that these proteins are widespread in nature. Based on these lines of evidence, we hypothesized that the frequency of extant fold-switching proteins may be underrepresented by the structures in the PDB. Thus, we sought to identify other putative extant fold switchers with only one solved conformation. To do this, we identified two characteristic features of our ∼100 extant fold-switching proteins, incorrect secondary structure predictions and likely independent folding cooperativity, and searched the PDB for other proteins with similar features. Reassuringly, this method identified dozens of other proteins in the literature with indication of a structural change but only one solved conformation in the PDB. Thus, we used it to estimate that 0.5–4% of PDB proteins switch folds. These results demonstrate that extant fold-switching proteins are likely more common than the PDB reflects, which has implications for cell biology, genomics, and human health.
The Treatment of Metastatic Thyroid Disease

Understanding of the importance of proper initial treatment of thyroid carcinoma and early detection of metastatic disease is essential. Proper treatment and early detection improve the overall survival rate in patients with thyroid carcinoma, and lead to a favorable condition in treatment of patients with metastatic thyroid carcinoma.
The State and Politics

Political Theory has been a shuttlecock between the historians and the philosophers for centuries, from the time of Thucydides and Plato. Today the social scientists claim it as part of their domain while philosophers have largely abandoned the attempt to enunciate political principles. The reason for this has been a preoccupation by philosophers with logical and epistemological analysis to which political philosophy seemed alien and which led its practitioners to view the elaboration of political creeds as mere ideology — a view which incidentally brought them into agreement with the sociologists.1 Such estrangement between philosophy and political theory is, however, abnormal and perverse, for the inescapable connexion between morality and social order ensures that ethics, inseparably bound on the one side with the philosophy of mind (and thus with metaphysics and epistemology), is equally enmeshed with the rationale of social and political institutions, on the other. This is not, of course, to say that history and social science have no part to play or that philosophers turning their attention to the principles of political order should neglect what the historian and the social scientist can reveal.
Connecting natural and artificial neural networks in functional brain imaging using structured sparsity

Artificial neural network models have long proven useful for understanding healthy, disordered, and developing cognition, but this work has often proceeded with little connection to functional brain imaging. We consider how analysis of functional brain imaging data is best approached if the representational assumptions embodied by neural networks are valid. Using a simple model to generate synthetic data, we show that four contemporary methods each have critical and complementary blind-spots for detecting distributed signal. The pattern suggests a new approach based on structured sparsity that, in simulation, retains the strengths of each method while avoiding its weaknesses. When applied to functional magnetic resonance imaging data the new approach reveals extensive distributed signal missed by the other methods, suggesting radically different conclusions about how brains encode cognitive information in the well-studied domain of visual face perception.
Using Cogenerative Dialogues to Transform Contradictions in Project-Based Learning

Project-based learning (PBL) has been suggested as an effective way to engage students meaningfully in science learning. However, there are many challenges when implementing PBL in teaching and learning (e.g., difficulty of assessing learning, students’ hesitation to seek help). This qualitative study investigated how cogenerative dialogues (cogens) can serve as a pedagogical tool to enhance the quality of teaching and learning in a PBL-styled student-scientist partnership program. Data sources included video recording of the internship and cogen activities, field notes, pictures, student journals, and individual interviews. Drawing on cultural-historical activity theory, we identified contradictions tangled with the complex interactions in activities that promoted changes and new developments in teaching and learning. Our analysis of two case studies suggests that cogens help students transform the contradictions in their activity systems into opportunities for becoming active learners, critical thinkers, and collaborative researchers. For transformation to occur, the contradictions must be recognized, reflected, and acted upon. The purposeful discussion about various contradictions in cogens allows participants to deeply reflect on their understandings about learning, teaching, and scientific practice and to disrupt their existing paradigms in order to negotiate new meanings and understandings to support students’ science learning.
Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease

Abstract Sandhoff disease (SD) results from mutations in the HEXB gene, subsequent deficiency of N-acetyl-β-hexosaminidase (Hex) and accumulation of GM2 gangliosides. SD leads to progressive neurodegeneration and early death. However, there is a lack of established SD biomarkers, while the pathogenesis etiology remains to be elucidated. To identify potential biomarkers and unveil the pathogenic mechanisms, metabolomics analysis with reverse phase liquid chromatography (RPLC) was conducted. A total of 177, 112 and 119 metabolites were found to be significantly dysregulated in mouse liver, mouse brain and human hippocampus samples, respectively (p 0.5). Principal component analysis (PCA) analysis of the metabolites showed clear separation of metabolomics profiles between normal and diseased individuals. Among these metabolites, dipeptides, amino acids and derivatives were elevated, indicating a robust protein catabolism. Through pathway enrichment analysis, we also found alterations in metabolites associated with neurotransmission, lipid metabolism, oxidative stress and inflammation. In addition, N-acetylgalactosamine 4-sulphate, key component of glycosaminoglycans (GAG) was significantly elevated, which was also confirmed by biochemical assays. Collectively, these results indicated major shifts of energy utilization and profound metabolic impairments, contributing to the pathogenesis mechanisms of SD. Global metabolomics profiling may provide an innovative tool for better understanding the disease mechanisms, and identifying potential diagnostic biomarkers for SD.
Developing an Optimized UI for Traffic Incident Managers

Traffic Incident Managers (TIMs) coordinate first responders and help resolve traffic-related incidents. Currently, some use over fifteen different software applications with unique functionalities...
The Importance of Theory for Reconstructing the Evolution of Language and Intelligence in Hominids

Although we anthropologists are academically licensed mythologists charged with explaining how “the man got his skin,” etc., our stories tend to suffer in plausibility from an absence of theory. In this paper we argue for the importance of theory for reconstructing the evolutionary history and adaptive significance of intelligence and language in our family.
Structure of human Vitronectin C-terminal domain and interaction with Yersinia pestis outer membrane protein Ail

Vitronectin (Vn) is a major component of blood that controls many processes central to human biology. It is a drug target and a key factor in cell and tissue engineering applications, but despite long-standing efforts, little is known about the molecular basis for its functions. Here, we define the domain organization of Vn, report the crystal structure of its carboxyl-terminal domain, and show that it harbors the binding site for the Yersinia pestis outer membrane protein Ail, which recruits Vn to the bacterial cell surface to evade human host defenses. Vn forms a single four-bladed β/α-propeller that serves as a hub for multiple functions. The structure explains key features of native Vn and provides a blueprint for understanding and targeting this essential human protein.
Wellens' Syndrome Presenting as Epigastric Pain and Syncope: An Unusual Presentation

Wellens' syndrome, also regarded as left anterior descending coronary T-wave syndrome, is an electrocardiography (EKG) pattern that indicates critical proximal left anterior descending artery (LAD) stenosis. It is characterized by deeply inverted T-waves or biphasic T-waves in the anterior precordial chest leads in a patient with unstable angina. Patients typically present with symptoms consistent with acute coronary syndrome. We present a unique case of Wellens' syndrome with no angiographic findings of significant stenosis in the proximal LAD but with significant occlusion of the proximal circumflex artery and initial presentation with a chief complaint of epigastric pain and syncope. Physicians need to recognize these characteristic EKG changes during the pre-infarction stage, as they represent myocardial necrosis. Many of these patients eventually develop extensive anterior myocardial infarction with marked left ventricular dysfunction and death if coronary angiography and coronary revascularization are not performed within a few weeks. If Wellens' is seen, patients should undergo urgent cardiac catheterization.
A Call for Help?: How Public School Principals’ Subjective Report of Institutional Weakness Relates to Disciplinary Incidents

Disciplinary incidents at U.S. public middle- and high-schools are a public policy concern. Although businesses popularly give credence to leaders’ subjective intelligence, principals’ reports of t...
The Dormant Foreign Commerce Clause After Wynne

This Essay surveys dormant foreign Commerce Clause doctrine to determine what limits it places on state taxation of international income, including both income earned by foreigners in a U.S. state and income earned by U.S. residents abroad. The dormant Commerce Clause similarly limits states’ powers to tax interstate and foreign commerce; in particular, it forbids states from discriminating against interstate or international commerce. But there are differences between the interstate and foreign commerce contexts, including differences in the nationality of affected taxpayers and differences in the impact of state taxes on federal tax and foreign-relations goals. Given current Supreme Court doctrine, we provide states guidance as to how to conform their regimes for taxing international income to constitutional requirements.
Fine scale alpha precipitation in Ti-19at.%v in the absence of influence from omega precipitates

Abstract While the isothermal omega-assisted mechanism of homogeneously distributed fine scale alpha precipitation has been well-documented in several titanium alloys, including Ti-19at%V (Ti-20wt%V), this paper reports that a similar type of alpha precipitation may occur in the absence of any direct or indirect influence of omega precipitates. Rapid heating of a beta solution-treated and quenched Ti-19at.%V alloy to 500 °C results in destabilization of the congruent athermal omega precipitates, followed by the development of compositional fluctuations in the form of Ti-rich or V-depleted pockets during isothermal holding, as revealed by atom probe tomography. These pockets possibly result from beta phase separation and may subsequently act as homogeneously distributed alpha nucleation sites.
The Fkh1 Forkhead Associated Domain Promotes ORC Binding to a Subset of DNA Replication Origins in Budding Yeast

The pioneer event in eukaryotic DNA replication is binding of chromosomal DNA by the Origin Recognition Complex (ORC), which directs the formation of origins, the specific chromosomal regions where DNA will be unwound for the initiation of DNA synthesis. In all eukaryotes, incompletely understood features of chromatin promote ORC-DNA binding. Here, we uncover a role for the Fkh1 (Forkhead homolog) protein, and, in particular, its forkhead associated (FHA) domain in promoting ORC-origin binding and origin activity at a subset of origins in Saccharomyces cerevisiae. The majority of the FHA-dependent origins within the experimental subset examined contain a distinct Fkh1 binding site located 59 of and proximal to their ORC sites (59-FKH-T site). Epistasis experiments using selected FHA-dependent origins provided evidence that the FHA domain promoted origin activity through Fkh1 binding directly to this 59 FKH-T site. Nucleotide substitutions within two of these origins that enhanced the affinity of their ORC sites for ORC bypassed these origins9 requirement for their 59 FKH-T sites and for the FHA domain. Significantly, direct assessment of ORC-origin binding by ChIPSeq provided evidence that this mechanism affected ~25% of yeast origins. Thus, this study reveals a new mechanism to enhance ORC-origin binding in budding yeast that requires the FHA domain of the conserved cell-cycle transcription factor Fkh1.
Anti-interleukin 8 autoantibody: interleukin 8 immune complexes visualized by laser confocal microscopy in injured lung: Colocalization with FcγRIIa in lung tissue from acute respiratory distress syndrome patients

•Context.-Anti-interleukin 8 autoantibody:interleukin 8 (anti-lL-8 autoantibody:lL-8) complexes are present in lung fluids of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and levels of these complexes correlate with progression to and the outcome of ARDS. FcyRlla, an immunoglobulin G (IgG) receptor, mediates proinflammatory activity of the complexes. Objective.-To evaluate lung tissues from patients with ARDS for presence of anti-lL-8 autoantibody:lL-8 complexes and to establish whether the complexes associate with FcyRlla. Design.-Lung tissue sections from 3 patients with ARDS and sections of normal lung tissues from 3 patients were stained with antibodies against IL-8 and IgG to detect immune complexes and with antibody against FcγRlla. In some experiments, sections were blocked with anti-Fcγ-Rlla antibody before staining. Samples were analyzed using confocal microscopy. Results.-Interleukin 8 costained with IgG and FcγRlla in lung tissues from patients with ARDS but not in control tissues, suggesting that anti-lL-8 autoantibody:lL-8 complexes are deposited in lungs of patients with ARDS via FcγRlla. Further, colocalization between IL-8 and FcγRlla could be blocked by anti-FcγRlla. Conclusions.-Our data demonstrate that anti-lL-8 autoantibody:lL-8 complexes are present in lung tissues of patients with ARDS, and are attached to FcγRlla.
A Synthesis of Subjective Scales Which Assess Worker Fatigue: Building a Simple, Reliable, and Effective Evaluative Instrument

The accurate assessment of operator fatigue has bedeviled ergonomics since before the field was formally constituted. From the archives of the British Industrial Fatigue Research Board in the pre-World-War I era, to Muscio’s (1921) famous inquiry “is a fatigue test possible?’ [1], the question of assessment has been a perpetual challenge. The lack of accurate assessment is allied to a ready recognition that fatigue plays a critical role in many large-scale disasters as well as errors and incidents of less social prominence, but which are nevertheless equally problematic. In recent decades, in our 24-7-365 world, the issue of operator fatigue continues to impact multiple millions of workers around the world; a propensity that the COVID-19 pandemic has only exacerbated. Yet all is not doom and gloom. Most especially in the 21st century, a number of promising methods and techniques have been offered to provide reliable, quantitative values which specify fatigue levels. Very much like the allied concern for workload assessment [2], the three primary methods of assessment concern primary task performance, physiological assessment approaches, and subjective evaluations. The present work is focused on the latter mode, being arguably the most useful for the prospective projection of future fatigue levels. In short, the issue of fatigue is a large and growing one, its assessment is a crucial ergonomic concern, synthesized subjective assessment techniques promise to provide a vital answer.
Adherence to PARP inhibitor therapy among women with ovarian cancer

Abstract Objective: The objective of this study was to evaluate medical adherence for patients with ovarian cancer who initiated treatment with a PARP inhibitor therapy, and to identify factors associated with nonadherence. Methods: We used the MarketScan Database to identify ovarian cancer patients who initiated PARP inhibitor therapy between January 1, 2008 and December 31, 2017. The primary outcome was adherence defined as ≥ 80% proportion of days covered (PDC). A secondary outcome included adherence assessed using the medication possession ratio (MPR). Multivariable logistic regression analysis was performed to assess relation between PDC and explanatory variables. Sensitivity analysis was performed to evaluate impact of dose-adjustments and toxicity-related delays on adherence. Results: Among 170,976 patients diagnosed with ovarian cancer, 151 patients met inclusion criteria. The median time from diagnosis to initiating therapy was 33 months. Overall, 40 (26.5%) were non-adherent based on a PDC less than 80%. Non-adherent patients were more likely to receive niraparib and have a longer duration of therapy (p Conclusion: This population based study of ovarian cancer patients found that a quarter of patients may be sub-optimally adherent to PARP inhibitor therapy. Future research should focus on identification of patients at risk for nonadherence and interventions to lower nonadherence among these patients.
Selective Ensembles for Consistent Predictions.

Recent work has shown that models trained to the same objective, and which achieve similar measures of accuracy on consistent test data, may nonetheless behave very differently on individual predictions. This inconsistency is undesirable in high-stakes contexts, such as medical diagnosis and finance. We show that this inconsistent behavior extends beyond predictions to feature attributions, which may likewise have negative implications for the intelligibility of a model, and one's ability to find recourse for subjects. We then introduce selective ensembles to mitigate such inconsistencies by applying hypothesis testing to the predictions of a set of models trained using randomly-selected starting conditions; importantly, selective ensembles can abstain in cases where a consistent outcome cannot be achieved up to a specified confidence level. We prove that that prediction disagreement between selective ensembles is bounded, and empirically demonstrate that selective ensembles achieve consistent predictions and feature attributions while maintaining low abstention rates. On several benchmark datasets, selective ensembles reach zero inconsistently predicted points, with abstention rates as low 1.5%.