cssi/SciSciGPT-SciSciNet huggingface dataset:
The Overall Systems Engineering Design

The mission/business analysis community typically attempted to keep analysis distinct from technical design. It is not inherently different or an incorrect term for development of a solution to a system design. In the end, the activities which we would call design are nothing different from the activities required to create the “To-be” requirements.
Resolving Behavioral Output via Chemogenetic Designer Receptors Exclusively Activated by Designer Drugs

Designer receptors exclusively activated by designer drugs (DREADDs) have proven to be highly effective neuromodulatory tools for the investigation of neural circuits underlying behavioral outputs. They exhibit a number of advantages: they rely on cell-specific manipulations through canonical intracellular signaling pathways, they are easy and cost-effective to implement in a laboratory setting, and they are easily scalable for single-region or full-brain manipulations. On the other hand, DREADDs rely on ligand-G-protein-coupled receptor interactions, leading to coarse temporal dynamics. In this review we will provide a brief overview of DREADDs, their implementation, and the advantages and disadvantages of their use in animal systems. We also will provide numerous examples of their use across a broad variety of biomedical research fields.
Flea-Borne Rickettsioses and Rickettsiae

Rickettsia typhi and Rickettsia felis are flea-borne rickettsiae that are distributed throughout the world. This mini-review outlines the ecology and epidemiology of flea-borne rickettsioses; highlights important clinical, diagnostic, and therapeutic considerations; and discusses areas of uncertainty regarding Rickettsia felis and other rickettsiae harbored by fleas.
Importance of Health-Related Fitness Knowledge to Increasing Physical Activity and Physical Fitness

Physical inactivity is expanding across all ages in the United States. Research has documented a deficiency in health-related fitness knowledge (HRFK) among elementary- through college-aged students. The need for a credible and reliable resource that provides research-based information regarding the importance of HRFK is significant. The purpose of this article was to examine the relationship between HRFK, physical activity (PA), and physical fitness (PF). This issue is particularly important for physical educators because of the growing concerns over rising obesity and declining levels of PA across the country. HRFK research to this point has indicated three important findings: (1) HRFK is low among elementary-aged students through college-aged students; (2) HRFK has successfully predicted PA and PF levels, though research is limited; and (3) educational interventions such as conceptual physical education (CPE) center on fitness knowledge, and their application has indicated a longitudinal increase in PA and PF levels.. This comprehensive review of literature is designed for the use of physical educators considering the adoption of health-related fitness education initiatives with the intent of improving long-term PA and PF.
A Review of Broadband Regional Discrimination Studies of NTS Explosions and Western U.S. Earthquakes

Verification of a Comprehensive Test Ban Treaty (CTBT) will require the use of seismic stations within regional distances (<2000 km). One important aspect of regional seismic monitoring involves the discrimination of nuclear explosions from other sources such as earthquakes and mining events (e.g. industrial explosions and rockbursts). In this paper, we review earthquake/nuclear explosion discrimination studies in the western U.S. using broad-band seismic data. These studies are important because they are the only ones involving nuclear explosions and other sources in a single geophysical region having excellent ground truth information and a substantial historic database. Additionally, because of access to information from the NTS, much can be learned about the physical basis of regional discriminants. Using multivariate discrimination techniques, it was found that approximately 96% of the events analyzed could be correctly identified down to about magnitude 3.5. Most of the events misidentified were recorded with poor signal-to-noise ratio at only a minimal number of stations. However, a few well-recorded events were misclassified for one or more discriminants. Examples of detailed analysis of a missed violation (nuclear explosion that looks like an earthquake) and a false alarm (naturally occurring event that looks like an explosion) are illustrated. Resolution of anomalous events such as these will be critical to CTBT monitoring.
Clinical Reasoning: A 22-year-old man with diplopia.

A 22-year-old previously healthy man presented to an ophthalmology clinic with binocular horizontal diplopia. He had recently traveled to the main island of Hawaii. About 2 weeks after returning home, he developed a severe headache with associated fever, emesis, photophobia, phonophobia, and neck stiffness. He also reported a sensation of pressure in his left eye and both ears but denied any pulsatile tinnitus or transient vision loss. Over the next 2 weeks, his headaches worsened, causing him to wake up frequently in the night. He then developed horizontal diplopia that was worse at a distance and was referred to the neuro-ophthalmology clinic.
How Managers Foster Trust Through Control and Trustworthiness

This paper contributes to control-trust research by describing how the efforts managers make to demonstrate their trustworthiness (integrity, ability, benevolence) moderate the effects of managerial controls (output, process, social) on subordinate trust. Our survey of managers and subordinates indicates three conditions under which subordinate trust increases: when managers apply output controls and demonstrate their integrity; when managers apply process controls and demonstrate their ability; when managers apply social controls and demonstrate their benevolence. We argue that that these relationships exist because when managers demonstrate their trustworthiness in ways that facilitate the achievement of performance objectives (i.e., specified in the controls managers apply), subordinates are more confident that authorities are committed to protecting and promoting their interests. The paper concludes with a discussion about how these perspectives advance research on organizational control, organization...
Evaluation of cathode contamination with Ca2+ in proton exchange membrane fuel cells

Abstract An ex-situ evaluation of the effects of Ca 2+ on the cathode of proton exchange membrane fuel cells was completed. A Ca 2+ concentration of 0.9 mM in the HClO 4 solution had no effect on the oxygen reduction reaction activity of a Pt/C catalyst. Upon increasing the Ca 2+ concentration to 9 and 90 mM, the availability of Pt active sites slightly decreased in the presence of Ca 2+ , and other observed effects included (i) a decrease in the kinetic and diffusion-limited currents; (ii) a decrease in the electron transfer number, and accordingly, an increase in H 2 O 2 formation; and (iii) an increase in the acid site occupation and a decrease in the O 2 permeability in the ionomer. The Ca 2+ cations that were absorbed in the ionomer reduced the mass-transport kinetics of O 2 and blocked the adsorption of O 2 on the Pt particles.
Contemporary debates on opportunity cost theory and pedagogy

Ferraro and Taylor’s (2005) finding that only 21.6% of economists could correctly answer a question on opportunity cost resulted in renewed debate over a fundamental concept. We review the lines of argument in a symposium on opportunity cost pedagogy and conclude that the confusion is due to the fact that opportunity costs are inappropriately presented alongside production tradeoffs in textbooks. We show that the traditional causal-realist ordinal and subjective conception of opportunity cost provides the desired clarity and consistency with real choice. Objections to the causal-realist opportunity cost concept in Reisman (1998) and Braun (2014) are also reviewed.
The influence of talker accent strength on accent categorization

Listeners' identification accuracy for nonnative-accented words tends to decrease as the talker's accent strength increases. However, the influence of accent strength on accent categorization has not been investigated. We hypothesized that nonnative talkers with stronger accents would have more salient cues to their native languages and thus, listeners would show increased accent categorization accuracy. To test this hypothesis, monolingual American English listeners categorized sentences produced by 12 native and 24 nonnative talkers in a 12-alternative forced-choice task with 8 nonnative accent categories and 4 regional dialect categories. Three talkers from each language/dialect background with different accent strengths (i.e., mild, moderate, strong) were included. The talkers' accent/dialect strengths were determined by 20 listeners' ratings on a 9-point scale (nonnative talkers: 1 = no foreign accent and 9 = very strong foreign accent; native talkers: 1 = Standard American English and 9 = very stron...
Early and Late Results of the Modified Fontan Operation for Heterotaxy Syndrome: 30 Years of Experience in 142 Patients

OBJECTIVES We sought to evaluate the early and late results of the modified Fontan operation for patients with heterotaxy syndrome, assess variables traditionally known to correlate with poor outcome, and assess current health status of survivors after the Fontan procedure. BACKGROUND The natural history of unoperated cardiac lesions in heterotaxy is known to be poor. Therefore, the Fontan operation has been proposed to improve survival. METHODS Patients with heterotaxy were identified from the Mayo Clinic Fontan database. Hospital and outpatient records were abstracted for preoperative, operative, and postoperative clinical and hemodynamic data. All patients not known to be deceased were sent health status questionnaires. RESULTS A total of 142 patients with heterotaxy syndrome had a modified Fontan operation. Asplenia was present in 76 patients (54%). Median age at operation was 9 years (range 2 to 35 years). Median follow-up was 4 years (range 0 to 23 years). There were a total of 61 deaths (43%), with 32 (23%) within 30 days of operation or before hospital discharge. The 5-, 10-, and 15-year survival was 64%, 57%, and 53%, respectively. In the modern era (1995 to 2004) early mortality was 10%. Of the 81 survivors, questionnaires were available from 41 (51%). Eighty percent reported having no or mild symptoms. However, 19 (46%) had arrhythmias, 5 (12%) had a thromboembolic event, and 1 (2%) developed protein-losing enteropathy. CONCLUSIONS Early survival has improved for heterotaxy patients after the Fontan operation; however, late morbidity and mortality remain substantial. Better strategies for long-term treatment of this high-risk group need to be identified.
Prostate Growth Factor: Characterization and its Role in Normal Prostate and in Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is the most common benign neoplastic growth that occurs in men. It has been estimated that 75% of males over 50 years of age have symptoms of urinary-outlet obstruction arising from BPH (Walsh, 1984). Birkhoff (1983) has estimated that the chance of a 50 year old requiring a prostatectomy during his lifetime is 20–25%. Over 350,000 surgical procedures are performed each year to relieve symptoms resulting from BPH, resulting in an overall medical cost that exceeds one billion dollars annually in the United States (Peters and Walsh, 1987). These statistics emphasize the need for new approaches to the study of BPH because, despite more than 100 years of study, the etiology of BPH has not been resolved.
The Quality of Life in Rural and Urban America

Considerable uncertainty exists about the quality of life to be found at present in rural America. In 1957, Max Lerner wrote movingly of the demise of the small town in rural America, observing that this form of settlement had been eclipsed by the forces of urbanization and mechanization. According to Lerner, it was no longer possible to restore the American small town to its previous state of strength and vitality (Lerner, 1957). This is not an uncommon view of rural and small-town America, which depicts the conditions and resources of these areas as seriously deficient relative to the rest of our society. Yet, this gloomy diagnosis and prognosis seem much diminished in more recent accounts of rural America. Bradshaw and Blakely (1979) speak of a “new rurality,” where the countryside is blossoming with resources and opportunities made possible by new transportaion and communication technologies and where new rural residents, part of the urban to rural “reverse migration,” bring new talents and energies to the small towns of America. One might ask whether it is only the experts and social analysts who are ambivalent about the present state of rural America. Consider, then, the contradiction expressed in the attitude of the American public toward rural living versus their actions with regard to actual residential location. On the one hand, Americans show a longstanding and continuing preference to live in small towns and rural areas’65% of a national survey sample indicated this preference in 1948, 49% in 1966, 55% in 1970, and 58% in 1976 (Elgin, Thomas, Logothetti, & Cox, 1974; Gallup, 1978). On the other hand, the actual movement of Americans has been, until very recently, largely from the small towns and the countryside into metropolitan areas. This suggests that Americans do hold a positive image of rural and small-town living, but that this pull is not sufficiently strong to overcome the attractions that the larger population centers offer.
Forest Nutrient Cycling: Influence of Trace Metal Pollutants

Nutrients must move into, within, and out of forest ecosystems in appropriate amounts, at appropriate rates and along established pathways for normal forest growth to occur. The two major sources of nutrients for temperate forest ecosystems are (1) meteorologic input of dissolved, particulate, and gaseous chemicals from outside the ecosystem ; and (2) release by weathering of nutrients from primary and secondary minerals stored within the ecosystem (Bormann and Likens, 1979). Healthy forest ecosystems conserve these nutrients and continually recycle them through the system via an elaborate litterfall-decomposition-uptake intrasystem cycle.
A RECIPE for Meaningful Gamification

Meaningful gamification is the use of gameful and playful layers to help a user find personal connections that motivate engagement with a specific context for long-term change. While reward-based gamification can be useful for short-term goals and situations where the participants have no personal connections or intrinsic motivation to engage in a context, rewards can reduce intrinsic motivation and the long-term desire to engage with the real world context. If the goal is long-term change, then rewards should be avoided and other game-based elements used to create a system based on concepts of meaningful gamification. This article introduces six concepts—Reflection, Exposition, Choice, Information, Play, and Engagement—to guide designers of gamification systems that rely on non-reward-based game elements to help people find personal connections and meaning in a real world context.
Design Rationale behind the Identity Metasystem Architecture

Many of the problems facing the Internet today stem from the lack of a widely deployed, easily understood, secure identity solution. Microsoft’s “InfoCard” project and the Identity Metasystem vision underlying it are aimed at filling this gap using technology all can adopt and solutions all can endorse, putting users in control of their identity interactions on the Internet. The design decisions presented in this paper are intended to result in a widely accepted, broadly applicable, inclusive, comprehensible, privacyenhancing, securityenhancing identity solution for the Internet. We present them and the rationale behind them to facilitate review of these design decisions by the security, privacy, and policy communities, so that people will better understand Microsoft’s implementations, and to help guide others when building interoperating implementations.
U.S. Cotton Industry Competitiveness in the Context of the Cotton Supply Chain

The U.S. cotton industry generates more than $25 billion in products and related services yearly, employing approximately 200,000 people in the various industry sectors from farms to textile mills (USDA, 2013a). Of the total cotton production in the United States, 75% is currently exported, leading to the importance of competitiveness of the U.S. cotton industry in a global setting. The United States has been the top cotton exporter in the world since 1989, accounting for nearly one-third of the world's cotton exports (USDA, 2013b). However, the market leadership has been consistently challenged, resulting in a significant decrease in the market share of the U.S. cotton export from 41.24% in 2004 to 26.70% in 2013 in the global cotton market (USDA, 2013b). Traditionally, the textile and apparel industries are considered an extended part of the cotton supply chain because textile and apparel industries have used and are using raw materials from the cotton industry to create final products for consumers at the final stage of the cotton supply chain (Rivoli, 2009). However, there has been little research to investigate how U.S. cotton industry competitiveness is affected in the context of the cotton supply chain. Based on this, there exists a need to understand the current competitiveness of the U.S. cotton industry, as well as how to improve this position on a global scale in the context of cotton supply chain. Therefore, the purpose of this research is to preliminarily explore factors that determine the competitiveness of the cotton industry in the context of cotton supply chain based on Porter's competitiveness factor model.
Floquet stability analysis of capsules in viscous shear flow

Observations in experiments and simulations show that the kinematic behaviour of an elastic capsule, suspended and rotating in shear flow, depends upon the flow strength, the capsule membrane material properties and its at-rest shape. We develop a linear stability description of the periodically rotating base state of this coupled system, as represented by a boundary integral flow formulation with spherical harmonic basis functions describing the elastic capsule geometry. This yields Floquet multipliers that classify the stability of the capsule motion for elastic capillary numbers ranging from to 5. Viscous dissipation rapidly damps most perturbations. However, for all cases, a single component grows or decays slowly, depending upon , over many periods of the rotation. The transitions in this stability behaviour correspond to the different classes of rotating motion observed in previous studies.
Issues in Serious Veterinary Illness and End-of-Life Care

Abstract Medical advances once unthinkable for animals have become standard care within veterinary practice. This is most notable in the management of serious veterinary illness, provision of intensive care services, and navigation of death and dying for veterinary patients. Given the inextricable link between companion animals and their people, mental health professionals have an increasingly critical role to play in contemporary veterinary practice. Familiarity with the unique challenges within veterinary end-of-life care, and the contextual issues related to, and preceding, animal-related grief and bereavement is important for addressing the human needs that arise. Attention to client support around treatment decision-making, euthanasia, palliative care, and hospice services, as well as knowledge of bioethical principles within veterinary medicine, are essential for mental health professionals who are involved in the complex world of serious veterinary illness and end-of-life care. Historically, mental health professionals have focused on grief and bereavement within veterinary settings; this has also been a common animal-related issue in psychotherapy practice. However, their role may be significantly expanded. Common issues which represent opportunities for mental health professionals include: family disagreement, financial strain, spiritual conflict, caregiver burden, traumatic past experiences with animal illness and death, traumatic past experiences with human illness, death, or medical care, and mental illness affecting decision-making capacity.
Warnings for Hurricane Irma: Trust of Warning Type and Perceptions of Self-Efficacy and Susceptibility:

The purpose of this study was to examine the types of risk communication received about Hurricane Irma by a university sample, along with their perceptions of self-efficacy and susceptibility to th...
Child Obesity and the Interaction of Family and Neighborhood Socioeconomic Context

The literature on neighborhoods and child obesity links contextual conditions to risk, assuming that if place matters, it matters in a similar way for everyone in those places. We explore the extent to which distinctive neighborhood types give rise to social patterning that produces variation in the odds of child obesity. We leverage geocoded electronic medical records for a diverse sample of over 135,000 children aged 2 to 12 and latent profile modeling to characterize places into distinctive neighborhood contexts. Multilevel models with cross-level interactions between neighborhood type and family socioeconomic standing (SES) reveal that children with different SES, but living in the same neighborhoods, have different odds of obesity. Specifically, we find lower-SES children benefit, but to a lesser degree, from neighborhood advantages and higher-SES children are negatively influenced, to a larger degree, by neighborhood disadvantages. The resulting narrowing of the gap in obesity by neighborhood disadvantage helps clarify how place matters for children’s odds of obesity and suggests that efforts to improve access to community advantages as well as efforts to address community disadvantages are important to curbing obesity and improving the health of all children.
Synthesis of ortho-Substituted Nitroaromatics via Improved Negishi Coupling Conditions.

The coupling products are useful intermediates for the synthesis of hydroxamic acids such as (XIV).
A Simple Introduction to Free Probability Theory and its Application to Random Matrices

Free probability theory started in the 1980s has attracted much attention lately in signal processing and communications areas due to its applications in large size random matrices. However, it involves with massive mathematical concepts and notations, and is really hard for a general reader to comprehend. The main goal of this paper is to briefly describe this theory and its application in random matrices as simple as possible so that it is easy to follow. Applying free probability theory, one is able to calculate the distributions of the eigenvalues/singular-values of large size random matrices using only the second order statistics of the matrix entries. One of such applications is the mutual information calculation of a massive MIMO system.
Extensive allopolyploidy in the neotropical genus Lachemilla (Rosaceae) revealed by PCR-based target enrichment of the nuclear ribosomal DNA cistron and plastid phylogenomics.

PREMISE OF THE STUDY Polyploidy has been long recognized as an important force in plant evolution. Previous studies had suggested widespread occurrence of polyploidy and the allopolyploid origin of several species in the diverse neotropical genus Lachemilla (Rosaceae). Nonetheless, this evidence has relied mostly on patterns of cytonuclear discordance, and direct evidence from nuclear allelic markers is still needed. METHODS Here we used PCR target enrichment in combination with high throughput sequencing to obtain multiple copies of the nuclear ribosomal (nr) DNA cistron and 45 regions of the plastid genome (cpDNA) from 219 accessions representing 48 species of Lachemilla and to explore the allopolyploid origin of species in this group. KEY RESULTS We were able to identify multiple nrDNA ribotypes and establish clear evidence of allopolyploidy in 33 species of Lachemilla, showing that this condition is common and widespread in the genus. Additionally, we found evidence for three autopolyploid species. We also established multiple, independent origins of several allopolyploid species. Finally, based solely on the cpDNA phylogeny, we identified that the monotypic genus Farinopsis is the sister group of Lachemilla and allied genera within subtribe Fragariinae. CONCLUSIONS Our study demonstrates the utility of the nuclear ribosomal DNA cistron to detect allopolyploidy when concerted evolution of this region is not complete. Additionally, with a robust chloroplast phylogeny in place, the direction of hybridization events can be established, and multiple, independent origins of allopolyploid species can be identified.
Late graft failure is rare after endovascular aneurysm repair using the Zenith stent graft in a cohort of high-risk patients.

Abstract Objective Device-specific data on the long-term efficacy of endovascular aneurysm repair (EVAR) are limited by the constant evolution of stent graft design. Whereas some modifications, such as barb-mediated fixation, probably enhance durability, others, such as thin-walled fabric, are of less certain benefit. The purpose of this study was to examine 15 years of a single-center experience of EVAR using the Zenith stent graft (Cook Medical, Bloomington, Ind). Methods Retrospective analysis was conducted of 325 high-risk patients who underwent elective EVAR with Zenith stent grafts between October 1998 and December 2005 under a physician-sponsored investigational device exemption. Patients' charts and death registries were reviewed to identify late stent graft failures and causes of death. Late stent graft failures were defined as type I or type III endoleaks; enlarging aneurysm sac requiring revision; and limb kinking or occlusion, stent graft infection, renal artery occlusion, or aneurysm rupture occurring >30 days after the index procedure. Results The mean age at treatment was 75.9 ± 7.4 years, and 300 of 325 (92%) were men. The mean aneurysm diameter was 60 ± 9 mm, and the median main body stent graft diameter was 28 mm (range, 22-32 mm). During a median follow-up time of 5.6 years (interquartile range, 2.6-8.7 years), there were six (2%) aneurysm-related deaths caused by the following: one stent graft infection, one infection of a femoral-femoral bypass graft placed after limb occlusion, one infection of a stent graft placed to treat a type IB endoleak, and three aneurysm ruptures. There were 19 (6%) late stent graft failures occurring at a median time of 4.0 years (range, 39 days-14.6 years) after the procedure. Patients with late stent graft failure were more likely to have had impaired renal function (creatinine concentration ≥2 mg/dL; 21% vs 6%; P = .03) and less likely to have had cardiac disease (42% vs 67%; P = .04) at the time of the index procedure. There was no significant association between late stent graft failure and age, sex, aneurysm size, stent graft diameter, diabetes, smoking, or lung disease. Kaplan-Meier estimated overall survival was 60% at 5 years, 29% at 10 years, and 12% at 15 years. Kaplan-Meier estimated freedom from aneurysm-related mortality was 98% at 5 years, 97% at 10 years, and 97% at 15 years. Conclusions Late-occurring stent graft failures and aneurysm-related death are rare after EVAR using the Zenith stent graft, especially in high-risk patients whose comorbidities diminish life expectancy.
Test of a Relationship between Spatial Working Memory and Perception of Symmetry Axes in Children 3 to 6 Years of Age.

Children’s memory responses to a target location in a homogenous space change from being biased toward the midline of the space to being biased away. According to Dynamic Field Theory (DFT), improv...
Targeting DNA damage response in head and neck cancers through abrogation of cell cycle checkpoints.

Purpose: Head and neck cancers (HNSCC) are routinely treated with radiotherapy; however, normal tissue toxicity remains a concern. Therefore, it is important to validate treatment modalities combin...
La palabra agusanada: estética del asco y materialismo orgánico en Los gemidos (1922) de Pablo de Rokha

En Los gemidos (1922), el poeta vanguardista chileno Pablo de Rokha muestra una peculiar obsesion por el motivo literario del cadaver en descomposicion. La imagen de la descomposicion corporal, ins...
Novel semi-automated algorithm for high-throughput quantification of adipocyte size in breast adipose tissue, with applications for breast cancer microenvironment.

The size distribution of adipocytes in fat tissue provides important information about metabolic status and overall health of patients. Histological measurements of biopsied adipose tissue can reve...
Abstract A62: A cerebral organoid model of pediatric glioma

Glioblastoma is the most devastating brain cancer with dismal prognosis both in adults and children and accounts for 16% of primary brain tumors. Despite aggressive therapeutic approaches, the majority of patients die within one year after diagnosis. Current in vivo modeling of glioblastoma involves xenografts either of cultured cell lines or human biopsies transplanted into mice. These models do not faithfully recapitulate the complex biology/pathogenesis of cancer. Here we used human pluripotent embryonic stem cells (or young children fibroblast-driven induced pluripotent stem cells) to create 3D structures with histology reminiscent of human fetal brain (the so-called cerebral organoids). Cerebral organoids combine the accurate multilineage differentiation and physiology of a developing brain with the easiness of manipulation of an in vitro system. We engineered these mini-brains to develop tumors by forced expression of combinations of epigenetic and genetic hits that have previously been shown to drive pediatric glioblastoma multiform (GMB). These include the expression of a mutant histone H3 variant H3F3A (mutated at K27M or G34R) or a gain of function of a mutant form of isocitrate dehydrogenase (IDH1R132H) in combination with the loss of ATRX histone remodeling factor and/or p53 tumor suppressor. Lentiviral transfection was used to express combination of these genetic and epigenetic hits into cerebral organoids. The mutated organoids exhibited tumorigenic growth that was histologically characterized. For example, the expression of H3K27M in combination with loss of both p53 and ATRX showed a remarkable dysplasia reminiscent of primary glioblastoma. Moreover, these organoids exhibited tumor rosette structures resembling those found in ependymoma. In contrast, organoids expressing K27M alone did not show such structures. Interestingly, IDH1R132H combined with p53 and ATRX loss resulted in different tumor morphology, suggestive of a possibility to model oncogenic dependence in pediatric GBM. Cerebral organoids could also be used as a model to study tumor invasion starting with glioma stem-like cells (GSCs, which are believed to be the tumor-initiating cells in GBM). Interestingly, the GSC cell line 923 (which does not invade mouse brain in vivo) invaded and formed a focal lesion in a cocultured organoid. The organoid-based cancer model presented here carries a promising potential to uncover the initiation and pathogenesis of pediatric tumors early in the developing brain. Note: This abstract was not presented at the conference. Citation Format: Amin Ismail, Demis Balamatsias. A cerebral organoid model of pediatric glioma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A62.
Deep learning quantification of percent steatosis in donor liver biopsy frozen sections.

Abstract Background Pathologist evaluation of donor liver biopsies provides information for accepting or discarding potential donor livers. Due to the urgent nature of the decision process, this is regularly performed using frozen sectioning at the time of biopsy. The percent steatosis in a donor liver biopsy correlates with transplant outcome, however there is significant inter- and intra-observer variability in quantifying steatosis, compounded by frozen section artifact. We hypothesized that a deep learning model could identify and quantify steatosis in donor liver biopsies. Methods We developed a deep learning convolutional neural network that generates a steatosis probability map from an input whole slide image (WSI) of a hematoxylin and eosin-stained frozen section, and subsequently calculates the percent steatosis. Ninety-six WSI of frozen donor liver sections from our transplant pathology service were annotated for steatosis and used to train (n = 30 WSI) and test (n = 66 WSI) the deep learning model. Findings The model had good correlation and agreement with the annotation in both the training set (r of 0.88, intraclass correlation coefficient [ICC] of 0.88) and novel input test sets (r = 0.85 and ICC=0.85). These measurements were superior to the estimates of the on-service pathologist at the time of initial evaluation (r = 0.52 and ICC=0.52 for the training set, and r = 0.74 and ICC=0.72 for the test set). Interpretation Use of this deep learning algorithm could be incorporated into routine pathology workflows for fast, accurate, and reproducible donor liver evaluation. Funding Mid-America Transplant Society
Molecular Features of Cancer-associated Fibroblast Subtypes and their Implication on Cancer Pathogenesis, Prognosis, and Immunotherapy Resistance

Purpose: Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, but a systematic investigation of their molecular characteristics and clinical relevance are lacking. Here, we sought to compare CAFs across multiple cancer types to identify critical molecular pathways activated in CAF subtypes, which may contribute to clinical outcome, disease progression, and immunotherapy resistance. Experimental Design: We performed integrated analysis of CAFs from melanoma, head and neck squamous cell carcinoma, and lung cancer, and identified the molecular characteristics that are distinctly active in each CAF subtype. Gene signatures for individual CAF subtypes were identified and used to study the association of subtype abundance with clinical outcome and immunotherapy resistance. Results: We identified six CAF subtypes (pan-CAF) shared across cancer types and uncovered the molecular characteristics and genetic pathways distinguishing them. Interestingly, these CAF subtypes express distinct immunosuppressive factors, such as CXCL12 and CXLC14, and stem cell–promoting factor IL6. In addition, we identified novel transcriptional drivers (MEF2C, TWIST1, NR1H3, RELB, and FOXM1) key to CAF heterogeneity. Furthermore, we showed that CAF subtypes were associated with different clinical outcomes and uncovered key molecular pathways that could activate or suppress cancer progression or were involved in resistance to anti-PD1 or anti–PD-L1 immunotherapy. Conclusions: Our study identifies the molecular characteristics of CAF subtypes shared across several cancer types, implicates cancer types that may benefit from CAF subtype targeted therapies, and identifies specific CAF subtypes associated with immunotherapy resistance.
Adult and Child Visiting at Urban Jails: Perspectives on Visitation Experiences and Policies among Visitors and People in Jail:

Growth in the US incarcerated population over recent decades has brought a burgeoning body of research on parent-child visitations in correctional facilities. In contrast to this research, which ha...
Development of a multifunctional neoglycoside auxiliary for applications in glycomics research

A novel, multifunctional, tetrazine-containing neoglycoside auxiliary has been synthesized in three steps and 28% overall yield. The oxyamine was conjugated with unprotected carbohydrates under aqueous conditions (pH = 4.7), with DMF as a cosolvent, to provide neoglycosides in yields ranging between 51% and 68%. This auxiliary displayed broad advantages in the isolation and purification of complex carbohydrate mixtures, compatibility during extension by glycosyltransferases, and direct conjugation to chemical probes. Furthermore, the auxiliary can be removed in 96% yield under acidic conditions (0.25% TFA in H2O) that leave glycosidic linkages intact. Thereby, the tetrazine-containing neoglycoside auxiliary can serve to facilitate future glycomics investigations.
Simulating the dynamics of self-regulation, emotion, grit, and student performance in cyber-learning environments

This research presents the results of development and validation of the Cyclical Self-Regulated Learning (SRL) Simulation Model, a model of student cognitive and metacognitive experiences learning mathematics within an intelligent tutoring system (ITS). Patterned after Zimmerman and Moylan’s (2009) Cyclical SRL Model, the Simulation Model depicts a feedback cycle connecting forethought, performance and self-reflection, with emotion hypothesized as a key determinant of student learning. A mathematical model was developed in steps, using data collected from students during their sessions within the ITS, developing solutions using structural equation modeling, and using these coefficients to calibrate a System Dynamics (SD) Simulation model. Results provide validation of the Cyclical SRL Model, confirming the interplay of grit, emotion, and performance in the ITS. The Simulation Model enables mathematical simulations depicting a variety of student background types and intervention styles and supporting deeper future explorations of dimensions of student learning.
Practical Applications of Shoring Up Shortfalls: Women, Retirement, and the Growing GigSupp Economy

In Shoring Up Shortfalls: Women, Retirement, and the Growing GigSupp Economy, from the Summer 2021 issue of The Journal of Retirement, authors Caroline Lewis Bruckner (of American University in Washington, DC) and Jonathan Barry Forman (of Oklahoma Collegeof Law in Norman, OK) explored the growth of gig work that people do to supplement their regular income (GigSupp work). Smartphone apps like Uber and DoorDash have driven the rise of online gig work, but most gig workers do traditional odd jobs offline. Most GigSupp workers are women, and there is little research on them—so the authors focused on the effects of GigSupp work on women’s retirement prospects. They found that many GigSupp workers underreport their income to the IRS and thus undermine their Social Security retirement income potential. This is because current tax laws do not require payors to report many types of payments they make to gig workers. Gig workers also have lower rates of saving for retirement. This is problematic for women gig workers, who are less likely to have full-time jobs and tend to have lower financial literacy. The authors recommended policy changes to improve tax reporting, allow tax withholding from gig worker pay, expand Social Security benefits, and provide financial literacy education.
Muscle stiffness in down syndrome and other mentally handicapped subjects.

An attempt was made to determine the effects of strength training on elbow flexor stiffness of Down syndrome, non-Down syndrome mentally handicapped, and nonhandicapped subjects. It was hypothesized that stiffness would be affected by the training. Results showed that only half of the individual subjects increased their maximum voluntary contraction (MVC) level as a result of the training and that premeasures and postmeasures of MVC were not significantly different for any of the three groups. As expected, for both premeasures and postmeasures, nonhandicapped subjects had a significantly higher MVC than the other groups who were not significantly different. An important finding was that measures of stiffness (slopes of the IEMG × Torque) were not significantly different for the three groups. This finding is consistant with recent studies (Davis & Kelso, 1982; Shumway-Cook & Woollacott, in press) but raises serious doubts about the popularly held opinion that Down syndrome individuals are hypotonic. It was...
The LDL pathway in human fibroblasts: a receptor-mediated mechanism for the regulation of cholesterol metabolism.

Publisher Summary Mammalian cells grow in culture because they have an ability to adapt to wide fluctuations in their nutrient supply. This adaptability implies that such cultured cells possess efficient regulatory mechanisms for the maintenance of metabolic homeostasis. Diploid mammalian cells, unlike haploid bacterial cells, are not readily amenable to the creation of specific metabolic blocks through induced mutation; hence, the powerful genetic techniques developed for study of metabolic regulation in bacteria are not applicable to mammalian cells. A regulated metabolic pathway in mammalian cells has been found, in which the availability of a series of naturally occurring mutants has permitted a combined biochemical and genetic study of metabolic regulation. This pathway, called the low density lipoprotein (LDL) pathway, consists of a sequence of discrete biochemical steps by which cultured cells take up, synthesize, and store cholesterol. The presence of this regulatory system in cultured cells suggested that non-hepatic cells might possess a system for the feedback regulation of cholesterol synthesis that was analogous to the feedback system that had been demonstrated in the livers of intact animals fed cholesterol.
Reverse transcription-PCR detection of LaCrosse virus in mosquitoes and comparison with enzyme immunoassay and virus isolation

A reverse transcription-PCR (RT-PCR) assay was developed and compared with enzyme immunoassay (EIA) and virus isolation for detecting LaCrosse virus (LAC) in mosquito pools. All three techniques were able to detect a single LAC-infected mosquito in a pool of 99 negative mosquitoes. Virus isolation was the most sensitive of the three techniques; it was possible to isolate virus immediately following intrathoracic inoculation of mosquitoes. RT-PCR was second in sensitivity; LAC RNA was detected 1 day postinfection. EIA detected LAC antigen 2 days postinfection. Additionally, RT-PCR and EIA were able to detect LAC RNA and protein, respectively, from mosquito samples which were subjected to seven freeze-thaw cycles, and RT-PCR was able to detect LAC RNA from mosquito samples which remained at room temperature for up to 7 days.
On estimating functional average breakthrough curve using time‐warping technique and perturbation approach

[1] Simulated contaminant breakthrough curves (BTC) are often used to predict mass arrival at compliance boundaries at waste storage sites. In numerical simulations that involve uncertainties on input parameters such as randomly heterogeneous rock properties, Monte Carlo simulations are commonly utilized and the mean breakthrough curve is often calculated from the arithmetic average of all realizations. The arithmetic mean breakthrough curve in general overestimates the mass flow rate at early and late time but underestimates the peak mass flow rate. The averaged breakthrough curve usually does not resemble any of individual breakthrough curves. The reason is that BTCs vary not only on amplitude but also on dynamics (time) and therefore it is not appropriate to take the arithmetic average directly. In this study, we consider each BTC as a random curve, and use time-warping techniques to align all curves in a time-warped space, compute the sample mean of the curves in the time-warped space, and transform the means back to the original time space. We show that all BTCs are aligned based on the percentile of mass reaching the compliance boundary, and the functional average is the percentile average of all BTCs. The confidence interval of the sample mean curve is estimated using the perturbation approach. The functional average provides an additional metric that can be used to characterize the breakthrough behavior in addition to more traditional median and arithmetic average curves. The method is illustrated using transport simulations at the Material Disposal Area G, Los Alamos National Laboratory (LANL) in New Mexico.
Fixpoints and Program Looping: Reductions form the Propositional MU-Calculus into Propositional Dynamic Logics of Looping

The propositional mu-calculus is a propositional logic of programs which incorporates a least fixpoint operator and subsumes the Propositional Dynamic Logic of Fischer and Ladner, the infinite looping constructs of Streett and Sherman, and the Game Logic of Parikh. The propositional mu-calculus is strictly stronger in expressive power than any of these other logics. However, the mu-calculus satisfiability problem is polynomially reducible to the satisfiability problem for Propositional Dynamic Logic with Streett's looping construct. This result shows the connection between fixpoints and program looping, provides an alternative decision procedure for the mu-calculus, and rules out the possibility that the complexities of the two logics could be separated by new upper and lower bound results. We also give reductions from several weaker mu-calculi (including those investigated by Kozen, Vardi and Wolper) into variants of Propositional Dynamic Logic with weaker looping constructs (including Sherman's looping construct). The deterministic exponential time upper bounds obtained for these mu-calculi may also be obtained via these reductions.
Effect of fluconazole on agar invasion by Candida albicans

Subinhibitory concentrations of azoles are known to inhibit hyphal branching of Candida albicans in liquid media. This study showed that subinhibitory concentrations of fluconazole also inhibit agar invasion by C. albicans in YPD solid medium. Agar invasion was markedly inhibited in two C. albicans strains that were resistant to fluconazole. This suggests that the degree to which fluconazole inhibits agar invasion by C. albicans hyphae could serve as a marker of susceptibility to azoles.
Sensitivity of Limulus amebocyte lysate (LAL) to LAL-reactive glucans.

The sensitivity of Limulus amebocyte lysate (LAL) to LAL-reactive glucans (LRGs) and lipid A was tested by using commercially available and experimentally formulated LAL reagents. The glucans included two kinds of beta-(1,3)-D-glucans, laminarin and curdlan, and cellulosic material, LAL-reactive material (LAL-RM), extracted from a hollow-fiber (Cuprophan) hemodialyzer. LAL-RM loses its LAL activity when it is digested with cellulase and thus appears to be a beta-(1,4)-D-glucan or a mixed glucan containing a substantial proportion of beta-(1,4) linkages. All LAL reagents tested were at least 1,000-fold more sensitive to endotoxin than to LRGs. The presence of the surfactant Zwittergent was shown to interfere with reactivity to LRGs; LAL reagents without added Zwittergent reacted more strongly to LRGs than did the same reagents containing Zwittergent. Chloroform extraction of LAL increased the reagents9 sensitivity to both endotoxin and LRGs, but it was not responsible for LRG reactivity. The addition of Zwittergent significantly reduced the sensitivity of LAL reagents to lipid A. LAL without the surfactant was equally sensitive to endotoxin and lipid A. Both curdlan and LAL-RM amplified or enhanced the LAL response to endotoxin. Kinetic turbidimetric studies demonstrated that the enhancement was dependent on the glucan concentration.