cssi/SciSciGPT-SciSciNet huggingface dataset:
Childhood hematologic cancer and residential proximity to oil and gas development

Background Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors.
A characterization of ℵ0-spaces

Abstract A new characterization is given for the ℵ0-spaces of E. Michael. It is known that if X and Y are ℵ0-spaces, then the space of maps from X to I, with the compact-open topology, is also an ℵ0-space. The characterization of ℵ0-spaces is used to show that there is a topology, called the cs-open topology, coarser than the compact-open topology even in the special case of the real functions on the unit interval, in which the mapping space from an ℵ0-space to an ℵ0-space is again an ℵ0-space. Other basic properties of the cs-open topology are given.
Primary and Secondary Caregiver Reports of Quality of Life in Pediatric Asthma: Are they Comparable?

This study aimed to compare primary and secondary caregiver QOL within families of children with asthma and determine the potential importance of including secondary caregiver QOL in clinical and research settings. Participants included 118 families of children with asthma that had primary and secondary caregivers. Families completed measures in a single research session. Caregivers reported on QOL, psychological functioning, and family burden; children completed a measure of QOL. Child lung function was determined from objective spirometry. Adherence to prescribed controller medication was measured for 6 weeks following the research visit. Primary caregiver QOL was significantly lower than secondary caregiver QOL (Mean overall QOL of 5.85 versus 6.17, p < .05). Better medication adherence was associated with higher primary caregiver QOL (ρ = .22, p = .02); secondary caregiver QOL, not primary caregiver QOL, was positively associated with child QOL (ρ = .20, p = .03). Families with discrepant QOL scores between caregivers (difference in scores of at least .50) were characterized by more family burden and primary caregiver psychological symptoms. Differences in QOL scores between caregivers may be a reflection of primary caregivers’ greater investment in daily asthma management. In families reporting low burden and few psychological difficulties in the primary caregiver, QOL assessments from either caregiver may may be informative and representative of how parents are adapting to child asthma. In families experiencing high levels of burden or more primary caregiver psychological difficulties, QOL reports from secondary caregivers may not be as clinically meaningful.
Secure Information Flow Verification with Mutable Dependent Types

This paper presents a novel secure hardware description language (HDL) that uses an information flow type system to ensure that hardware is secure at design time. The novelty of this HDL lies in its ability to securely share hardware modules and storage elements across multiple security levels. Unlike previous secure HDLs, the new HDL enables secure sharing at a fine granularity and without implicitly adding hardware for security enforcement; this is important because the implicitly added hardware can break functionality and harm efficiency. The new HDL enables practical hardware designs that are secure, correct, and efficient. We demonstrate the practicality of the new HDL by using it to design and type-check a synthesizable pipelined processor implementation that support protection rings and instructions that change modes.
Accessibility in Pedestrian Routing

Pedestrian route planning presents unique challenges compared to relatively well established car routing applications. The challenges are even more pronounced when also considering a diverse user group, which includes people with disabilities. Existing research has identified environmental features that are important to pedestrians with disabilities, but there are still a number of outstanding problems that have hindered the development of a widespread, usable solution. We developed the EUG Access web application (http://geog.uoregon.edu/geocog/eugaccess) to implement an approach to pedestrian routing that incorporates environmental accessibility and responds to the needs and preferences of a diverse user population. This paper reviews related literature and reports our experience through three phases of development: personalization , route calculation, and interface design. It concludes by drawing attention to issues that we propose are critical to successfully incorporating environmental accessibility into future pedestrian routing applications.
Medicaid Adult Dental Benefit Impact on Dental Utilization: A University Clinic Setting

Introduction: In 2014 the state of Colorado initiated new dental coverage benefits for adults in the Colorado Medicaid program. The goal of this study was to investigate the utilization and impact of this new dental coverage at the University of Colorado School of Dental Medicine. The utilization of dental services delivered and the numbers of patients in this program were compared before and after the implementation of the benefit. Material and Methods: This retrospective study compared the utilization of services provided 2-years prior and 2-years after the Medicaid adult benefit was made available. Through the University of Colorado School of Dental Medicine (CU- SODM) electronic dental record, all adult Medicaid dental patients’ (ages 21+) charts were extracted for zip code, CDT dental procedure codes, with a focus on tooth extraction compared to tooth saving procedures. Graphical analysis and Pearson’s Chi-Squared tests were applied to assess the statistical significance of procedure utilization changes over time. Results: After implementation of the Medicaid adult benefit, the number of patients seen at the school under this program increased by a factor of 4.5. The geographic range (zip code) increased with a some patients coming from further distances to receive dental care. The number of patients from local zip codes increased by as much as 235 %. There was a 51 % increase in tooth saving procedures, which was statistically significant (P = 0.0013). Additionally, there was a 22 % decrease in extractions, while not statistically significant (P = 0.0992), a downward trend was clear. Discussion: The focus was on the utilization of Medicaid adult benefits at the dental school which was only a small proportion of the state-wide Medicaid population. Therefore, this data is not generalizable for statewide assessments of the program. However, based on the findings at the school clinics, more adult patients utilized the benefits; and chose to receive more tooth saving procedures and less extractions after implementation of the Medicaid adult benefit. This Medicaid study conducted at the CU-SODM 2-years after the adult dental coverage can be used as a baseline for future studies. Word count: 343
Gene transcription patterns in response to low level petroleum contaminants in Mytilus trossulus from field sites and harbors in southcentral Alaska

Abstract The 1989 Exxon Valdez oil spill damaged a wide range of natural resources, including intertidal communities, and post-spill studies demonstrated acute and chronic exposure and injury to an array of species. Standard toxicological methods to evaluate petroleum contaminants have assessed tissue burdens, with fewer assays providing indicators of health or physiology, particularly when contaminant levels are low and chronic. Marine mussels are a ubiquitous and crucial component of the nearshore environment, and new genomic technologies exist to quantify molecular responses of individual mussels to stimuli, including exposure to polycyclic aromatic hydrocarbons (PAHs). We used gene-based assays of exposure and physiological function to assess chronic oil contamination using the Pacific blue mussel, Mytilus trossulus . We developed a diagnostic gene transcription panel to investigate exposure to PAHs and other contaminants and its effects on mussel physiology and health. During 2012–2015, we analyzed mussels from five field sites in western Prince William Sound, Alaska, with varying oil histories from the 1989 Exxon Valdez oil spill, and from three boat harbors in the area. Gene transcription patterns of mussels from harbors were consistent with elevated exposure to PAHs or other contaminants, whereas transcription patterns of mussels sampled from shorelines in areas affected by the oil spill indicated no PAH exposure.
Improving the Accessibility of Patient Care Through Integration of the Hospital and Radiation Oncology Electronic Health Records

PurposeRadiation therapy (RT)–specific aspects of a patient’s cancer care commonly are documented and scheduled through a radiation oncology electronic health record (rEHR). However, patients who receive RT also receive multidisciplinary care from providers who use the hospital EHR (hEHR). We created an electronic interface to integrate our hEHR and rEHR to improve communication of the RT aspects of care between our department and the rest of the hospital. The objective of this study was to assess the impact of rEHR and hEHR integration on the accessibility of the RT-specific aspects of patient care to providers.Methods and MaterialsWe performed a preintegration and postintegration survey of 175 staff members at our academic cancer center. Respondents rated the importance and accessibility of several RT encounters and documents on a Likert scale. The Wilcoxon-Mann-Whitney, χ2, and Fisher’s exact tests were used to compare preintegration and postintegration responses.ResultsThere were 32 and 19 responses t...
On the genus Tylorida Simon, 1894 with the first record of the genus Atelidea Simon, 1895 from India (Araneae: Tetragnathidae, Leucauginae)

The tetragnathid spider genus Tylorida Simon, 1894 is reviewed in India. The relationship of Tylorida with Orsinome Thorell, 1890 is discussed and illustrated. The taxonomic significance of male chelicerae of Tylorida spp. is discussed and an identification key based on the features of male chelicerae to separate Indian Tylorida spp. is provided. A new species, Tylorida flava sp. nov. is described and illustrated. Two new transfers and four new synonyms are proposed: Orsinome marmorea Pocock, 1901 and Tylorida culta (O. Pickard-Cambridge, 1869) are transferred to Tylorida and Mesida Kulczyn'ski, 1911 respectively, Tylorida cylindrata (Wang, 1991) and Tylorida sataraensis Kulkarni, 2014 are synonymised with Tylorida marmorea (Pocock, 1901) comb. nov., Tylorida nicobarensis (Tikader, 1977) is synonymised with Tylorida striata (Thorell, 1877) and Leucauge pondae Tikader, 1970 is synonymised with Tylorida ventralis (Thorell, 1877). The biology, natural history and intraspecific variations of T. marmorea comb. nov. are noted. The occurrence of intraspecific variations and colour polymorphism in T. ventralis is discussed and two colour morphs (Silver and Yellow morphs) and three varieties (varieties I, II & III) for the species are recognised. Additionally, the genus Atelidea Simon, 1895 is recorded for the first time from India and provided the description and illustration of Atelidea nona sp. nov.. The current distribution of Atelidea is mapped.
Organoids lead the cancer attack

In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.
The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K (gK) Is Required for gB Binding to Akt, Release of Intracellular Calcium, and Fusion of the Viral Envelope with Plasma Membranes

Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino-terminal 38 amino acids of gK prevents herpes simplex virus 1 (HSV-1) infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 phosphorylated at S473 [Akt-1(S473)] confirmed that HSV-1(McKrae) gB interacted with Akt-1(S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced the release of intracellular calcium. In contrast, the gB specified by HSV-1(McKrae) gKΔ31-68, lacking the amino-terminal 38 amino acids of gK, failed to interact with Akt-1(S473) and induce intracellular calcium release. The Akt inhibitor miltefosine inhibited the entry of McKrae but not the gKΔ31-68 mutant into SK-N-SH cells. Importantly, the entry of the gKΔ31-68 mutant but not McKrae into SK-N-SH cells treated with the endocytosis inhibitors pitstop-2 and dynasore hydrate was significantly inhibited, indicating that McKrae gKΔ31-68 entered via endocytosis. These results suggest that the amino terminus of gK functions to regulate the fusion of the viral envelope with cellular plasma membranes.IMPORTANCE HSV-1 glycoprotein B (gB) functions in the fusion of the viral envelope with cellular membranes during virus entry. Herein, we show that a deletion in the amino terminus of glycoprotein K (gK) inhibits gB binding to Akt-1(S473), the release of intracellular calcium, and virus entry via fusion of the viral envelope with cellular plasma membranes.
Controls of embedded HVDC system for system dynamic performance enhancement

Low-frequency inter-area oscillation, a common phenomenon in the power transmission, has led to many system separations and a few wide-scale blackouts. The embedded HVDC system is a possible solution to this issue when equipped with a proper control. In an embedded HVDC system, at least two HVDC terminals are physically connected within the same meshed ac network. This paper proposed a coordination control strategy for embedded HVDC systems to attenuate low-frequency inter-area oscillations. The transient studies are performed in the PSCAD platform. According to the simulation results, the test system average critical clearing time is improved by 29.2% when with the proposed strategy compared to the system without it.
Lung Cancer: Posttreatment Imaging: Radiation Therapy and Imaging Findings

In this review, we discuss the different radiation delivery techniques available to treat non-small cell lung cancer, typical radiologic manifestations of conventional radiotherapy, and different patterns of lung injury and temporal evolution of the newer radiotherapy techniques. More sophisticated techniques include intensity-modulated radiotherapy, stereotactic body radiotherapy, proton therapy, and respiration-correlated computed tomography or 4-dimensional computed tomography for radiotherapy planning. Knowledge of the radiation treatment plan and technique, the completion date of radiotherapy, and the temporal evolution of radiation-induced lung injury is important to identify expected manifestations of radiation-induced lung injury and differentiate them from tumor recurrence or infection.
The relationship between race competitiveness, standing in the polls, and social media communication strategies during the 2014 U.S. gubernatorial campaigns

Political campaigns have been systematically using social media for strategic advantage. However, little is known about how competitiveness affects the ways candidates communicate online. Our study...
Guidelines and Technical Aspects in Face Composite Tissue Transplantation

Face transplantation combines the surgical complexity of multiple subspecialties that require an organized systematic approach to the evaluation of potential face transplant candidates, donors and surgical team members. Once established, the face transplant team should comprise of the scientific, clinical and surgical expertise than can orchestrate a successful operation on a well chosen patient. Our efforts at the Cleveland Clinic’s Department of Plastic Surgery first face transplantation procedure revealed guidelines and technical aspects in facial composite tissue transplantation that can guide other institutions in their efforts to expand composite tissue transplantation as not just a state-of-the-art surgery but rather the future standard of care for those debilitated patients that have exhausted all facets of facial reconstruction. This chapter is meant as only a guideline since each subsequent face transplantation patient will require a custom made surgical approach to both the donor face delivery and transplant procedure.
Rosaceaous Genome Sequencing: Perspectives and Progress

The long-term goal of plant genomics is to identify, isolate and determine the function of plant genes that are associated with both vegetative and reproductive phenotypes. Most phenotypes require the coordinated activity and regulatory control of suites of genes over time and in precise positions within the plant. Until recently, the idea of establishing a comprehensive approach to isolate and characterize all the genes involved in any complex phenotype was a daunting one, and oftentimes it has been necessary to perform whole genome sequencing to obtain all of the gene sequences. The sequence of several plant genomes have been generated including the Arabidopsis, poplar and rice genomes, with the model legume Medicago and sorghum well underway. In addition, large amounts of expressed sequence tag (EST) information are being obtained for many other plants, including rosaceaous plants. The advances in genomics, informatics, and phylogenetics have been developed and refined by these reference projects, to the point that it is now thought that, in many cases, the vast majority of genes of a plant can be identified without the complete genome sequence, however the EST approach to gene identification does not provide valuable information regarding promoters and other non-coding regulatory elements. One of the first eukaryotic genomes to be completely sequenced was that of the small mustard species Arabidopsis thaliana. During the past decade, Arabidopsis has emerged as one of the most widely used model organisms for studying the biology of higher plants. Its genome was chosen for sequencing because it is highly compact, about 125 Mb, with little interspersed repetitive DNA (Arabidopsis Genome Initiative, 2000). However, since Arabidopsis is rather distantly related to the cereal crops that provide the bulk of the world food supply, the genome of rice has also been sequenced. Rice was chosen because, in addition to its importance as a food source for about one quarter of the human population, it has one of
Effects of long-term oxygen therapy on mortality and morbidity.

Abstract In general, based on the above studies of the effects of supplemental oxygen on reducing mortality and improving sleep and exercise function in certain patient groups, patients whose disease is stable on a full medical regimen with PaO2 < or = 55 mm Hg (SaO2 < or = 88%) should be considered for LTOT. Patients with PaO2 of 55-59 mm Hg with signs of tissue hypoxemia (i.e., cor pulmonale, polycythemia, impaired cognition) should also be considered for LTOT. Oxygen therapy should also be considered for those who desaturate during sleep or exercise. These guidelines have been adopted by Medicare as reimbursement criteria and have also been endorsed by the American Thoracic Society. Indications for LTOT endorsed by the American Thoracic Society and published in the "Standards for the Diagnosis and Care of Patients with COPD" are shown in Table 6. More research is required to investigate the use of supplemental oxygen in patients who suffer nocturnal desaturation but do not have signs of end organ dysfunction, those who have an improvement in dyspnea with supplemental oxygen, and in normoxemic patients with impaired exercise performance who improve while inspiring supplemental oxygen.
Antigen-Binding Receptors on Lymphoid Cells. Nature and Specificity of Receptors on Various Types of Immunocompetent Cells

Publisher Summary This chapter discusses antigen-binding receptors on lymphoid cells. It describes experiments aimed at evaluating the receptors possessed by the various types of immunocompetent cells involved in response of guinea pigs to a hapten-homologous protein conjugate [2,4-dinitrophenyl guinea pig albumin (DNP-GPA)]. In these experiments extensive use of two general techniques introduced for the evaluation of antigen-binding receptors was made. They were (1) specific adsorption of antigen-binding cells to antigen particle conjugates, with subsequent analysis of the nonadsorbed cells; and (2) visualization and enumeration of antigen-binding lymphocytes by radioautographic detection of radioactive antigen bound to the surface membrane of such cells. Results demonstrated that 125I-DNP-GPA ABC bear receptors very likely immunoglobulin in nature and mainly of the γ2 class, and these receptors have a considerable degree of hapten specificity. The removal of such cells from lymph node and spleen cells suspensions either by cytolysis with anti-Ig and complement or by specific adsorption to antigen–agarose beads diminishes the ability of the cell population to transfer primary responsiveness to a DNP protein to irradiated syngeneic animals.
Regulation of natural cytotoxic activity.

DISCUSSION INTRODUCER GUSTAVO CUDKOWICZ: If naturally occurring cytotoxic cells are to fulfill an important biological function, they will be integrated and they will be regulated. Only in the last few years have studies been conducted on NK cell regulation. In trying to present an overview of these studies, I concluded that the best approach was to follow the chronology of these studies.
A content analysis of how STEM education researchers discuss the impact of their publicly-supported research

Impact is a topic of interest among a wide range of stakeholders interested in engineering workforce development but is onein which there is a dearth of scholarship. While existing literature includes two dimensions of research impact (scientific,and societal), this qualitative study proposes and focuses on the third dimension—contextual impact. Using Toulmin’sModel and theCommon Guidelines for Education Research and Development, this study uses content analysis to explorehow researchers on National Science Foundation-funded STEM education RD special attention is given to engineering education research.Findings reveal eight claims that are commonly discussed when Principal Investigators articulate research impact; twothemes relate to how their claims are supported. The findings also indicate that the discipline associated with the study andthe project focus has more to do with the types of impact PIs claim than the amount of funding awarded to the project. TheproposedSCS Impact Frameworkresulted from identifying the points of alignment between PIs’ perspectives on impactand existing literature. This conceptual lens describing impact in this context is useful for researchers, practitioners, andpolicymakers around the world interested in the scientific, contextual, and societal dimensions of engineering educationR&D.
Forecasting the 8 May 2017 Severe Hail Storm in Denver, Colorado, at a Convection-Allowing Resolution: Understanding Rimed Ice Treatments in Multimoment Microphysics Schemes and Their Effects on Hail Size Forecasts

AbstractDay-ahead (20–22 h) 3-km grid spacing convection-allowing model forecasts are performed for a severe hail event that occurred in Denver, Colorado, on 8 May 2017 using six different multimom...
Caught in the Act

Which came first, the stars and gas that make up a galaxy, or the giant black hole at its centre? Observations of a distant galaxy, caught as it forms, could help solve this chicken-and-egg problem.
"Taming the Elephant in the (Class)room: Exploring Root Causes of Student Boredom".

Despite being a pervasive emotion that is felt across occupational and educational contexts, boredom has heretofore been underexplored in the marketing education literature. This research attempts ...
Factors Associated With Postoperative Infection After Percutaneous Nephrolithotomy

Numerous studies have investigated risk factors for the development of postoperative infection in percutaneous nephrolithotomy (PCNL) patients. Herein, we describe our meta-analysis of the risk factors for the prediction of post-PCNL infectious complications. We searched electronic databases using a combination of the terms percutaneous nephrolithotomy, risk factors, infection, and sepsis. The primary outcome was post-PCNL infection as defined by fever >38°C or sepsis as defined by the Sepsis Consensus Definition Committee. Risk factors for infection in each study were identified and included for analysis if present in at least two studies. We used quantitative effect sizes in odds ratio to assess each endpoint. After application of criteria, 24 studies were found, of which 12 were prospective and 12 were retrospective. Of the prospective studies, preoperative urine culture, renal pelvis culture, stone culture, number of access points, hydronephrosis, perioperative blood transfusion, and struvite stone composition were found to be significantly associated with postoperative infection. Of the 12 retrospective studies, preoperative urine culture, stone cultures, number of access points, blood transfusion, stone size, and staghorn formation were associated with infection. Preoperative urine culture, stone culture, number of access points, and need for blood transfusion were consistently found to be significant factors. This indicates that the presence of bacteria in the urine/stone preoperatively as well as the amount of trauma the kidney sustains during the procedure are major predictors of postoperative infection.
Why do people volunteer

Abstract This chapter provides an overview of why people volunteer for disasters. The chapter begins with a brief consideration of how disaster volunteering has evolved over time. A subsequent section then explains why people volunteer in such challenging circumstances. The chapter concludes with a review of how volunteering benefits communities, volunteers, and recipients. In this chapter, case examples include the Johnstown flood (1889), the Indian Ocean tsunami (2004), hurricane Katrina (2005), the Haiti earthquake (2010), and the Japan tsunami/earthquake (2011) among others.
Coordination of Juxtaposed Muscle Layers as Seen in Hydra

Fish guts, rabbit oviducts, worms, blood vessels and Hydra share with each other the problem of coordinating juxtaposed layers of muscle. In Hydra, as in the viscera of vertebrates, there is now compelling evidence that this coordination is essentially mediated by nerves acting on sheets of electrically conducting muscle cells. In fact, the best way to look at Hydra, is probably to see it as a miniature vertebrate gut with nematocysts and tentacles. Looking at it in this way immediately causes much of its behavioral system to fall into place.
Vibrational Spectroscopic Monitoring of the Gelation Transition in Nafion Ionomer Dispersions.

Infrared and Raman spectroscopy techniques were applied to investigate the drying and aggregation behavior of Nafion ionomer particles dispersed in aqueous solution. Gravimetric measurements aided ...
COX-2 inhibition promotes IFNγ-dependent enhancement of anti-tumor immunity and vaccine response in lung cancer models

6056 Despite the identification of a repertoire of tumor antigens, hurdles persist for successful immune-based therapies. The active immune suppression induced by the tumor itself is a problem of paramount importance. In previous studies, we have demonstrated an immune suppressive network in non-small cell lung cancer that is due to over expression of tumor cyclooxygenase 2 (COX-2). In this study, we assessed the vaccination response to tumor challenge following pharmacological or genetic inhibition of COX-2 in a murine lung cancer model. Treatment of naive mice with the COX-2 inhibitor, SC-58236, skewed splenocytes toward a Type 1 cytokine response, inducing IFNγ, IL-12 and IP-10. Fifty percent of mice receiving SC-58236 and a sub-optimal irradiated tumor cell vaccine completely rejected tumors on rechallenge. In contrast, all mice vaccinated with either irradiated tumor cells alone or receiving SC-58236 alone showed progressive tumor growth. Studies performed in CD4 and CD8 knockout mice revealed a requirement for CD4 T lymphocyte subset for complete rejection of tumors following SC-58236 and a sub-optimal irradiated tumor cell vaccine administration. To determine the role of COX-2 expression on the vaccination responses, studies were performed in COX-2 gene knockout mice. Compared to control littermates, COX-2 -/- mice showed a significant reduction in tumor growth following vaccination with a sub-optimal dose of irradiated tumor cells. Compared to homozygous COX-2 -/- knockout mice, heterozygous COX-2 -/+ vaccinated mice had an intermediate reduction in tumor growth. In vivo depletion of IFNγ abrogated the COX-2 inhibitor-mediated vaccination effect. These findings provide a strong rationale for further evaluation of COX-2 inhibition in tumor immunity and its use to enhance vaccination responses against cancer.
Immunotherapy in metastatic sarcomatoid renal cell carcinoma: A single institution experience.

Abstract Introduction Immune checkpoint inhibitors (CPIs) were recently approved in advanced clear cell renal cell carcinoma (RCC) and could be a promising option for metastatic RCC with sarcomatoid differentiation (sRCC) which otherwise carry a poor prognosis. We sought to compare outcomes between patients who received immunotherapy (IO) including CPIs or high dose interleukin-2 (HD IL2) for metastatic sRCC versus those who did not. Patients and Methods We performed a single-center retrospective data analysis of 44 consecutive sRCC patients with any percentage of sarcomatoid differentiation from our institutional RCC database of whom 34 received IO and 10 patients did not. Results Baseline variables between the two groups were not significantly different except for a greater percentage of patients with ≥40% sarcomatoid differentiation in the non-IO cohort. At a median follow-up of 27.6 months, patients treated with IO had a median overall survival of 57.6 months compared to 6.6 months in patients not treated with IO (p = 0.0002). Overall response rates (ORR) between the IO and non-IO group were 35.3% and 0% respectively (p = 0.06). When IO was given in the 1st line setting, the ORR was 25.0%, as compared to 44.4% in the 2nd line setting and beyond though limitations of small sample sizes apply. Immune-related adverse events (IRAE) occurred in 38.2% of patients in the IO group, with grade 3 events (mostly gastrointestinal) in 20.6% with no grade 4 or 5 events. IRAEs led to interruption or discontinuation of immunotherapy in 26.5%. Conclusion Our results support IO as an effective therapeutic option for patients with metastatic sarcomatoid RCC. Further study of various IO regimens, including those affecting the interleukin-2 signaling pathway, and their efficacy in neoadjuvant and adjuvant settings are warranted in sRCC.
Understanding Sunflower syndrome: Results of an online questionnaire.

Abstract Objective To characterize the clinical phenotype, treatments, and impact on quality of life of Sunflower syndrome. Methods A 138-question survey was created focusing on seizure description, disease course, treatment history, medical history, family history, and aspects of quality of life of individuals with Sunflower syndrome. The survey was administered to individuals with Sunflower syndrome who experience hand waving episodes (HWE) and/or their caregivers via Research Electronic Data Capture (REDCap). Results Sixty-eight responses were included in analysis. Seventy-one% of respondents were female. The mean age of participants was 13.6 years, with 84% of respondents under the age of 18. The average age of onset of HWE was 6.7 years. HWE frequency varied from a few episodes per week to multiple episodes per hour. Sixty-two% of participants experienced other seizure types. Participants had been on an average of 1.9 anti-seizure medications with varying efficacy. Other methods to reduce HWE included wearing a hat or sunglasses, hand holding, using special tinted lenses, and avoiding the sun and bright lights. Sixty-nine% of participants reported anxiety or depression related to their epilepsy, and 65% said their HWE affected their social life. Significance Sunflower syndrome is a highly stereotyped, refractory epilepsy which significantly impacts the lives of affected individuals. It remains underrecognized and poorly understood. These results characterize Sunflower syndrome in a large population of affected individuals and provides a basis for future research to better understand the epilepsy and improve clinical care.
Longitudinal evaluation of whole blood miRNA expression in firefighters.

BACKGROUND Dysregulated microRNA (miRNA) expression could provide a mechanism linking firefighter exposure to increased cancer risk. OBJECTIVE To determine if changes in longitudinal miRNA expression in firefighters are associated with occupational exposures. METHODS Whole blood MiRNA was evaluated in 52 new recruits prior to live-fire training and 20-37 months later. Linear mixed effects models adjusted for age, ethnicity, BMI, and batch effects were used to determine associations separately for all fires and structure fires only between employment duration, cumulative fire-hours and fire-runs, and time since most recent fire with (1) nine a priori and (2) the full array of 799 miRNAs. RESULTS For multivariable models including all fires, two a priori miRNAs were associated with employment duration and four with time since most recent fire. For multivariable models restricted to structure fires, three a priori miRNAs were associated with employment duration and one with fire-runs. Additional miRNAs from the full array were associated with employment duration for all fires and/or structure fires. In general, tumor suppressive miRNAs decreased and oncogenic miRNAs increased with exposure. SIGNIFICANCE Changes in miRNAs may serve as biomarkers of exposure effects and a mechanism for increased cancer risk in firefighters.
Developmental Effects on Relative Use of PEPCK and NADP-ME Pathways of C4 Photosynthesis in Maize

Abstract C4 photosynthesis is an adaptive photosynthetic pathway which concentrates CO2 around Rubisco in specialized bundle sheath cells to reduce photorespiration. Historically, the pathway has been characterized into three different subtypes based on the decarboxylase involved, although recent work has provided evidence that some plants can use multiple decarboxylases, with maize in particular using both the NADP-malic enzyme (NADP-ME) pathway and phosphoenolpyruvate carboxykinase (PEPCK) pathway. Parallel C4 pathways could be advantageous in balancing energy and reducing equivalents between bundle sheath and mesophyll cells, in decreasing the size of the metabolite gradients between cells and may better accommodate changing environmental conditions or source to sink demands on growth. The enzyme activity of C4 decarboxylases can fluctuate with different stages of leaf development, but it remains unclear if the pathway flexibility is an innate aspect of leaf development or an adaptation to the leaf microenvironment that is regulated by the plant. In this study, variation in the two C4 pathways in maize were characterized at nine plant ages throughout the life cycle. Two positions in the canopy were examined for variation in physiology, gene expression, metabolite concentration, and enzyme activity, with particular interest in asparagine as a potential regulator of C4 decarboxylase activity. Variation in C4 and C3 metabolism was observed for both leaf age and canopy position, reflecting the ability of C4 pathways to adapt to changing microenvironments. One Sentence Summary The proportion of the two C4 pathways in maize plants is dependent on canopy position and not the age of the leaf.
Rational Method Time of Concentration Can Underestimate Peak Discharge for Hillslopes

AbstractThe Rational Method remains one of the most widely used approaches for estimating peak discharge in small catchments. In one widely used interpretation of the Rational Method, the maximum p...
Systemic oxytocin increases glutamate efflux in the nucleus accumbens core of cocaine-experienced male and female rats but only increases dopamine efflux in males.

Abstract Oxytocin attenuates cocaine-seeking when administered both systemically and directly into the nucleus accumbens core . This effect is blocked by intra-accumbens antagonism of mGlu2/3 and, together with our finding that intra-accumbens oxytocin increases glutamate concentrations in this brain region, indicates that pre-synaptic regulation of glutamate release by oxytocin influences cocaine relapse. However, mGlu2/3 receptors also regulate dopamine release in the nucleus accumbens . Here we aimed to determine whether systemic oxytocin increases glutamate and dopamine concentrations in the nucleus accumbens core of cocaine-experienced and cocaine-naive male and female rats. A subset of rats self-administered cocaine (0.5 mg/kg/infusion) and then underwent extinction training for 2–3 weeks. Rats were implanted with microdialysis probes in the accumbens core and samples were collected for a baseline period, and following saline (1 mL/kg), and oxytocin (1 mg/kg, IP) injections. Locomotion was assessed during microdialysis. In cocaine-experienced rats, oxytocin increased glutamate concentrations in the accumbens core to the same extent in males and females but only increased dopamine concentrations in male rats. Oxytocin did not alter glutamate levels in cocaine-naive rats. Oxytocin did not produce sedation. These results extend previous findings that systemic oxytocin increases nucleus accumbens dopamine in a sex-specific manner in cocaine-experienced rats. These data are the first to find that systemic oxytocin increases nucleus accumbens glutamate after cocaine experience, providing a mechanism of action by which oxytocin attenuates the reinstatement of cocaine seeking in both male and female rats.
Rotational movement during cyclic nucleotide-gated channel opening.

Cyclic nucleotide-gated (CNG) channels are crucial components of visual, olfactory and gustatory signalling pathways. They open in response to direct binding of intracellular cyclic nucleotides and thus contribute to cellular control of both the membrane potential and intracellular Ca2+ levels1. Cytosolic Ni2+ potentiates the rod channel (CNG1) response to cyclic nucleotides2,3,4 and inhibits the olfactory channel (CNG2) response5. Modulation is due to coordination of Ni2+ by channel-specific histidines in the C-linker, between the S6 transmembrane segment and the cyclic nucleotide-binding domain. Here we report, using a histidine scan of the initial C-linker of the CNG1 channel, stripes of sites producing Ni2+ potentiation or Ni2+ inhibition, separated by 50° on an α-helix. These results suggest a model for channel gating where rotation of the post-S6 region around the channel's central axis realigns the Ni2+-coordinating residues of multiple subunits. This rotation probably initiates movement of the S6 and pore opening.
Base Pairing in DNA: Unusual Patterns

Watson–Crick base pairs comprise just two of 44 reasonable base pairing geometries involving the four common deoxyribonucleotides (dA, dC, dG, dT) in either their neutral or protonated forms. Most of the 42 non-Watson–Crick base pairs have been observed experimentally in DNA. Although these unusual base pairs are difficult to detect in vivo, unusual base pairing may be significant for the biological functions of DNA. Keywords: mutation; transversion; transition; telomere; I-motif; Hoogsteen
Parallel Quasi-Monte Carlo Methods on a Heterogeneous Cluster

We introduce a new parallelization scheme for low-discrepancy sequences. Our approach is similar to the parameterization approach used for pseudorandom number generators. We present a theoretical analysis of this scheme and compare it numerically with the conventional blocking and leap-frogging parallelization strategies, when they are applied to problems from option pricing and transport theory. The numerical results suggest that our scheme might be very useful especially in distributed computing environments with unreliable and heterogeneous clusters.
Lessons from privatization in Britain

Abstract The process of privatizing most of Britain's major public enterprises yields interesting conclusions on the three related issues: (1) A problem of policy assignment arose in the use of privatization and liberalization to achieve both allocative and productive efficiency. (2) Evidence on the behavior of the public enterprises is consistent with an organizational model of the relevant principal-agent relationships predicting certain types of slack absorption. (3) The privatization process entailed policy choices that bear on their future productive efficiency (effectiveness of monitoring by the market for corporate control) and allocative efficiency (provision for regulation).
A Rare Complication of Paraneoplastic Autoimmune Disorder in Langerhans Cell Histiocytosis (P3.149)

Objective: We report a case of LCH in a 64-year-old man who presented with symptoms and signs of diencephalon and brainstem dysfunction. Background: A 64-year-old right-handed Hispanic male presented with two-year history of vague symptoms including fatigue, weight loss, loss of libido, personality changes and possible seizure like events. He was first diagnosed with diabetes insipidus, hypothyroidism and severe depression. His initial examination was remarkable for ocular bobbing, right central facial nerve palsy and mild quadriparesis with spasticity. All routine blood works were negative apart from fluctuated serum sodium level. All CSF tests including complete paraneoplastic panel were negative except minimally elevated cell count with lymphocyte and macrophage. Brain imaging showed lytic bone lesion, T2 hyperintense lesions in the left frontal lobe, right mesial temporal lobe and brainstem which were minimally contrast enhancing. Left frontal bone lesions biopsy showed positive immunohistochemistry stained for CD1a and S100 which led to diagnosis of LCH. Right temporal second lesion showed reactive astrocytes with eosinophils which was neurodegenerative lesion. Hospital course is complicated by status epilepticus, septic shock and pulmonary embolism. Patient eventually improved with IV immunoglobulin and Cladribine. Conclusions: Grois et al in 2005 described three types of LCH neuropathology. Type one is the typical circumscribed granuloma. Type two is infiltrating granuloma with profound T-cell dominated inflammation and severe neurodegeneration. Type three is only neurodegenerative lesion without LC and typically affecting brainstem and cerebellum. The presence of inflammation without LC has led to the view that these lesions are autoimmune in origin. In our case, temporal lobe lesions are of second type and brainstem lesions are typical of third type. Neurodegeneration associated with this condition is a rare complication. There is currently no specific treatment of this complication. CD1a antibiodies and treatment along the lines of T-cell mediated paraneoplastic disorders have been tried Disclosure: Dr. Aung has nothing to disclose.
Architecture of rod and cone circuits to the on-beta ganglion cell

Photoreceptors connect to the on-beta ganglion cell through parallel circuits involving rod bipolar (RB) and cone bipolar (CB) neurons. We estimated for a small patch in the area centralis of one retina the 3- dimensional architecture of both circuits. This was accomplished by reconstructing neurons and synapses from electron micrographs of 189 serial sections. There were (per mm2) 27,000 cones, 450,000 rods, 6500 CBb1, 30,300 RB, 4100 All amacrines, and 2000 on-beta ganglion cells. The tangential spread of processes was determined for each cell type, and, with the densities, this allowed us to calculate the potential convergence and divergence of each array upon the next. The actual numbers of cells converging and diverging were estimated from serial sections, as were the approximate numbers of chemical synapses involved. The cone bipolar circuit showed narrow convergence and divergence: 16 cones----4 CBb1----1 on-beta 1 cone----1 CBb1----1.2 on- beta This circuit is thought to contribute significantly to the on-beta cell9s photopic receptive field because the CBb1 has a center-surround receptive field whose center diameter is greater than the spacing between adjacent CBb1s. Consequently, the receptive fields of the CBb1s converging on a beta cell are probably largely concentric and thus mutually reinforcing in their contributions to the on-beta. The rod bipolar circuit showed a wider convergence and divergence: 1500 rods---- 100 RB----5 AII----4 CBb1----1 on-beta 1 rod----2 RB----5 AII----8 CBb1- ---2----2 on-beta The 1500 rods converging via this circuit account for the spatial extent of the beta cell9s dark-adapted receptive field. This convergence also accounts for the ganglion cell9s maintained discharge, which is thought to arise from about 6 quantal “dark events” per second. This many dark events would appear in the ganglion cell if each rod in the circuit contributed 0.004 dark events per second, and this is close to what has been measured in monkey rods (Baylor et al., 1984). Divergence in this circuit serves to expand the number of copies of the quantal signal (1 rod----8 CBb1) and so to engage large numbers of chemical synapses that provide amplification. Reconvergence at the last stage (8 CBb1----2 on-beta) may reduce (by signal averaging) the synaptic noise that would otherwise accumulate along the pathway.