cssi/SciSciGPT-SciSciNet huggingface dataset:
Understanding the Requirements for Open Source Software

This study presents findings from an empirical study directed at understanding the roles, forms, and consequences arising in requirements for open source software (OSS) development efforts. Five open source software development communities are described, examined, and compared to help discover what differences may be observed. At least two dozen kinds of software informalisms are found to play a critical role in the elicitation, analysis, specification, validation, and management of requirements for developing OSS systems. Subsequently, understanding the roles these software informalisms take in a new formulation of the requirements development process for OSS is the focus of this study. This focus enables considering a reformulation of the requirements engineering process and its associated artifacts or (in)formalisms to better account for the requirements when developing OSS systems. Other findings identify how OSS requirements are decentralized across multiple informalisms, and to the need for advances in how to specify the capabilities of existing OSS systems.
Homologous desensitization of pancreatic beta cells to glucose response by polyunsaturated fatty acids

Abstract We have shown recently that a mixture of 10 m M linoleic acid (18:2,ω6) and 5 m M linoleic acid (18:3,ω3) enhanced insulin secretion by microdissected islets. In the present study, our aim was to examine the effect of a prestimulus with this mixture of 10 m M linoleic acid and 5 m M linoleic acid on glucose and arginine-stimulated insulin response, by perifused isolated islets. Insulin secretion by untreated (control) islets estimated as integrated area under the curve (AUC/ 20 mins) above basal during three pulses of 27.7 m M glucose separated by 20 min periods of basal (washout) perifusions were 2950 ± 585 pg, 5185 ± 1258 pg, and 2410 ± 921 pg, a greater response (P M arginine. These data suggest that (1) a mixture of 10 m M linoleic acid and 5 m M linolenic acid can desensitize isolated perifused islets to glucose but not arginine; and (2) glucose intolerance associated with lipemia may result, at least in part, from a direct effect on the islets of Langerhans.
Education and Poverty: Confronting the Evidence

Current U.S. policy initiatives to improve the U.S. education system, including No Child Left Behind, test-based evaluation of teachers, and the promotion of competition are misguided because they either deny or set to the side a basic body of evidence documenting that students from disadvantaged households on average perform less well in school than those from more advantaged families. Because these policy initiatives do not directly address the educational challenges experienced by disadvantaged students, they have contributed little—and are not likely to contribute much in the future—to raising overall student achievement or to reducing achievement and educational attainment gaps between advantaged and disadvantaged students. Moreover, such policies have the potential to do serious harm. Addressing the educational challenges faced by children from disadvantaged families will require a broader and bolder approach to education policy than the recent efforts to reform schools. C � 2012 by the Association
Umeclidinium/vilanterol combination inhaler efficacy and potential impact on current chronic obstructive pulmonary disease management guidelines

Introduction: Umeclidinium bromide (UM) with vilanterol (VI) is the first once-daily long-acting muscarinic antagonist/long-acting β2 agonist (LAMA/LABA) combination approved for use in the treatment of chronic obstructive pulmonary disease (COPD) in the USA. Prior to this, only combinations of short-acting bronchodilators and short-acting muscarinic antagonists were available in the USA as a single inhaler and they required frequent dosing. LAMA or LABA therapy is the recommended first choice for moderate-to-very severe COPD with combination therapy added if monotherapy fails to control patients’ symptoms. This allows lower dosing of individual medications, which may limit adverse effects. It could also have the additional benefit of improving patient compliance by making medication regimens less laboring.Areas covered: A comprehensive literature search of journal articles and abstracts looking for trials that evaluated both the efficacy and the safety of UM/VI revealed that UM/VI improves patients’ lung...
Designer’s preferences regarding equality constraints in robust design optimization

Robust design optimization (RDO) problems can generally be formulated by appropriately incorporating uncertainty into the corresponding deterministic optimization problems. Equality constraints in the deterministic problem need to be carefully formulated into the RDO problem because of the strictness associated with their feasibility. In this context, equality constraints have been generally classified into two types: (1) those that must be satisfied regardless of uncertainty, examples include physics-based constraints, such as F = ma, and (2) those that cannot be satisfied because of uncertainty, which are typically designer-imposed, such as dimensional constraints. This paper addresses the notion of preferred degree of satisfaction of deterministic equality constraints under uncertainty. Whether or not a particular equality constraint can be exactly satisfied depends on the statistical nature of the design variables that exist in the constraint and on the designer’s preferences. In this context, this paper puts forth three contributions. First, we develop a comprehensive classification of equality constraints in a way that is mutually exclusive and collectively exhaustive. Second, we present a rank-based matrix approach to interactively classify equality constraints, which systematically incorporates the designer’s preferences into the classification process. Third, we present an approach to incorporate the designer’s intra-constraint and inter-constraint preferences for designer-imposed constraints into the RDO formulation. Intra-constraint preference expresses how closely a designer wishes to satisfy a particular constraint; for example, in terms of its mean and standard deviation. A designer may express inter-constraint preference if satisfaction of a particular designer-imposed constraint is more important than that of another. We present an optimization formulation that incorporates the above discussed constraint preferences, which provides the designer with the means to explore design space possibilities. The formulation entails interesting implications in terms of decision making. Two engineering examples are provided to illustrate the practical usefulness of the developments proposed in this paper.
Structure Strategy Interventions: Increasing Reading Comprehension of Expository Text.

In this review of the literature we examine empirical studies designed to teach the structure strategy to increase reading comprehension of expository texts. First, we review the research that has served as a foundation for many of the studies examining the effects of text structure instruction. Text structures generally can be grouped into six categories: comparison, problem-and-solution, causation, sequence, collection, and description. Next, we provide a historical look at research of structure strategy interventions. Strategy interventions employ modeling, practice, and feedback to teach students how to use text structure strategically and eventually automatically. Finally, we review recent text structure interventions for elementary school students. We present similarities and differences among these studies and applications for instruction. Our review of intervention research suggests that direct instruction, modeling, scaffolding, elaborated feedback, and adaptation of instruction to student performance are keys in teaching students to strategically use knowledge about text structure.
Influence of buffalograss management practices on Western chinch bug and its beneficial arthropods.

A 2-yr study was conducted to document the influence of selected buffalograss, Buchloe dactyloides (Nuttall) Engelmann, management practices (three mowing heights and five nitrogen levels) on the seasonal abundance of the western chinch bug, Blissus occiduus Barber (Heteroptera: Lygaeidae), and its beneficial arthropods. Vacuum, pitfall, and sticky traps samples were collected every 14 d from the middle of May through October from western chinch bug-resistant (‘Prestige’) and -susceptible (‘378’) buffalograss management plots. In total, 27,374 and 108,908 western chinch bugs were collected in vacuum and pitfall traps, respectively. More than 78% of all western chinch bugs were collected from the highly susceptible buffalograss 378. Significantly more bigeyed bugs (Geocoridae: Geocoris spp.) were collected from the 378 buffalograsss management plots than the Prestige plots. In contrast, buffalograss cultivar had little influence on the abundance of other beneficial arthropods collected. Statistically, western chinch bugs were least abundant at the lowest mowing height (2.5 cm) and increased in abundance with increasing fertility. Numerically, however, differences among management levels on western chinch bug abundance were minimal. Numerous beneficial arthropods were collected from buffalograss management plots, including spiders, predatory ants, ground beetles (Carabidae), rove beetles (Staphylinidae), bigeyed bugs, and several species of hymenopterous parasitoids. In general, beneficial arthropods were essentially unaffected by either mowing height or nitrogen level. Scelionid wasps represented 66.3% of the total parasitoids collected. The total number of scelionid wasps collected among the three mowing heights and five nitrogen levels were approximately equal.
Toward a Boron-Doped Ultrananocrystalline Diamond Electrode-Based Dielectrophoretic Preconcentrator

This paper presents results on immunobeads-based isolation of rare bacteria and their capture at a boron-doped ultrananocrystalline diamond (BD-UNCD) electrode in a microfluidic dielectrophoretic preconcentrator. We systematically vary the bead surface chemistry and the BD-UNCD surface chemistry and apply dielectrophoresis to improve the specific and the nonspecific capture of bacteria or beads. Immunobeads were synthesized by conjugating antibodies to epoxy-/sulfate, aldehyde-/sulfate, or carboxylate-modified beads with or without poly(ethylene glycol) (PEG) coimmobilization. The carboxylate-modified beads with PEG provided the highest capture efficiency (∼65%) and selectivity (∼95%) in isolating live Escherichia coli O157:H7 from cultures containing 1000 E. coli O157:H7 colony-forming units (cfu)/mL, or ∼500 E. coli O157:H7 and ∼500 E. coli K12 cfu/mL. Higher specificity was achieved with the addition of PEG to the antibody-functionalized bead surface, highest with epoxy-/sulfate beads (85−86%), followe...
Modified Conjugate Gradient Method for the Solution of A {\underline x} = {\underline b}

In this note, we examine a modified conjugate gradient procedure for solving A {\underline x} = {\underline b} in which the approximation space is based upon the Krylov space (({\mathscr K}^k_{\sqrt {A}, {\underline b}})) associated with sqrt {A} and {\underline b}. We show that, given initial vectors {\underline b} and \sqrt {A} \, {\underline b} (possibly computed at some expense), the best fit solution in {\mathscr K}^k_{\sqrt {A}, {\underline b}} can be computed using a finite-term recurrence requiring only one multiplication by A per iteration. The initial convergence rate appears, as expected, to be twice as fast as that of the standard conjugate gradient method, but stability problems cause the convergence to be degraded.
Lessons Learned from the 2010 AIAA Shock Boundary Layer Interaction Prediction Workshop

High fidelity, physics-based computational modeling capability is required to design and analyze the next generation of high speed inlets. Shock boundary layer interactions represent a flow phenomenon that must be accurately modeled to improve high speed inlet designs. A shock boundary layer interaction workshop was held to assess the current state of the art in computational fluid dynamics for this class of flow, to learn how to collect validation quality data, to evaluate validation metrics, and to identify areas requiring more research and development. This paper summarizes the key lessons learned from the workshop.
Monitoring of Potential Bleed Air Gas Contaminants with FTIR Spectroscopy

A bleed-air system within an aircraft is very beneficial in that the compressed air that it produces can be used as a major power source for many environmental control systems from de-icing the wings of a plane to pressurizing the cabin. An issue of this system though, is that it has the potential to allow contaminated air from the environment during taxiing operations, as well as noxious gases due to possible leaks of engine oil, hydraulic fluid, deicing fluid, etc., into the aircraft cabin. This paper demonstrates the ability to monitor combusted oil contaminants that could potentially be present in an aircraft cabin environment using a Fourier Transform Infrared (FTIR) spectroscopy instrument (Perkin Elmer, Shelton, CT, USA). In cases where gas contaminants are not easily identifiable or separable within the FTIR spectra, a principal component analysis (PCA) technique is utilized to better distinguish the various compounds resulting from the combustion event as well as calculating the corresponding concentrations. The calculation of unknown concentrations of target compounds in the combusted oil samples are computed from a principal component regression (PCR) on simulated multi-component IR spectra. The components within the combusted oil samples were verified though mass spectroscopy from an outside laboratory. This data analysis has the potential to help identify and refine commercial sensors that could potentially be used to continuously monitor the air quality within an aircraft cabin or aircraft bleed-air system.
Abstract 843: Spontaneous immortalization of human mammary epithelial cells from a woman with a germline STK11 mutation

Spontaneous immortalization of benign mammary epithelial cells (MEC) in culture is very rare. Models of MEC immortalization suggest that cells escape M0 growth arrest (selection) by silencing p16 expression after which they encounter a second growth arrest, M1 (agonescence), characterized by telomere shortening and profound genomic instability. Pre-selection, post-selection, and spontaneously immortalized MEC from a woman with a germline STK11 mutation were subjected to a comprehensive “OMICS” evaluation including miRNA, transcriptome, methylome, exome, and comparative genomic hybridization (CGH) in order to understand the molecular events associated with MEC immortalization. Principle component analysis of gene expression identified 4 significant components, the first of which showed the greatest separation between the different time points. The most notable expression changes were upregulation of FOXQ1, IL1-related genes, Ras-related genes, and fibronectin and downregulation of COL1, COL6, CK19, and CDH1. MEC gradually acquired global hypomethylation of non-CpG DNA and regional hypermethylation of CpG islands (including p16). A classifier based on methylation pattern showed that immortalized cells moved away from identity with The Cancer Genome Atlas (TCGA) benign samples towards TCGA breast cancer samples. Immortalization was associated with a modest accumulation of mutations and a modestly greater number of DNA copy number alterations than was observed in earlier passage cells but no evidence of general genomic instability. Immortal cells showed a large deletion at 10q13-15 and deletions at 10p11-15 and 17p11-13 that were associated with reduced expression of genes in those regions. Post-selection bulk cell populations are quite distinct from early passage cells, but are not direct precursors of the immortal cells as some DNA copy number alterations acquired by post-selection cells were not observed in the immortalized cells. Rather, in this instance, it is likely that post-selection cells established conditions conducive to the immortalization of a rare cell in the mix. This has implications for the development of tissue-based approaches for breast cancer risk stratification. Citation Format: David Euhus, Dawei Bu, Michael Considine, Leslie Cope. Spontaneous immortalization of human mammary epithelial cells from a woman with a germline STK11 mutation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 843.
Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer

Purpose: To determine the expression level, associations, and biological role of PD-L1, IDO-1, and B7-H4 in non–small cell lung cancer (NSCLC). Experimental Design: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4, and different tumor-infiltrating lymphoycte (TIL) subsets in 552 stages I–IV lung carcinomas from two independent populations. Associations between the marker levels, TILs, and major clinicopathologic variables were determined. Validation of findings was performed using mRNA expression data from The Cancer Genome Atlas (TCGA) and in vitro stimulation of lung adenocarcinoma A549 cells with IFNγ and IL10. Results: PD-L1 was detected in 16.9% and 21.8% of cases in each population. IDO-1 was expressed in 42.6% and 49.8%; and B7-H4 in 12.8% and 22.6% of cases, respectively. Elevated PD-L1 and IDO-1 were consistently associated with prominent B- and T-cell infiltrates, but B7-H4 was not. Coexpression of the three protein markers was infrequent, and comparable results were seen in the lung cancer TCGA dataset. Levels of PD-L1 and IDO-1 (but not B7-H4) were increased by IFNγ stimulation in A549 cells. Treatment with IL10 upregulated B7-H4 but did not affect PD-L1 and IDO-1 levels. Conclusions: PD-L1, IDO-1, and B7-H4 are differentially expressed in human lung carcinomas and show limited co-expression. While PD-L1 and IDO-1 are associated with increased TILs and IFNγ stimulation, B7-H4 is not. The preferential expression of discrete immune evasion pathways in lung cancer could participate in therapeutic resistance and support design of optimal clinical trials. Clin Cancer Res; 23(2); 370–8. ©2016 AACR.
Prognostic factors in traumatic atlanto-occipital dislocation.

Traumatic atlanto-occipital dislocation (AOD) is an ominous injury with high mortality and morbidity in trauma patients. Improved survival has been observed with advancements in pre-hospital and hospital care. Furthermore, high quality imaging studies are accessible at most trauma centers; these are crucial for prompt diagnosis of AOD. The objective of this study is to perform a comprehensive literature review of traumatic AOD, with specific emphasis on identifying prognostic factors for survival. A review of the literature was performed using the Medline database for all traumatic atlanto-occipital articles published between March 1959 and June 2015; 141 patients from 60 total studies met eligibility criteria for study inclusion. A binary logistic regression model was utilized to identify prognostic factors. The analysis assessed age, sex, spinal cord injury (SCI), traumatic brain injury (TBI), polytrauma injury (PI), and Traynelis AOD Classification. Only TBI was statistically significantly associated with death (OR 8.05 p 0.05). Age, sex, PI, and Traynelis AOD Classification did not meet significance to predict mortality in AOD patients. We found that patients with TBI are eight times more likely to die than patients without TBI. A high degree of suspicion for AOD during pre-hospital care, as well as, prompt diagnosis and management in the trauma center play a key role in the treatment of this devastating injury. The relationship between survival and factors such as TBI and SCI should be further explored.
Socioeconomic Differences in Use of Low-Value Cancer Screenings and Distributional Effects in Medicare.

Objective Consuming low-value health care not only highlights inefficient resource use but also brings an important concern regarding the economics of disparities. We identify the relation of socioeconomic characteristics to the use of low-value cancer screenings in Medicare fee-for-service (FFS) settings, and quantify the amount subsidized from nonusers and taxpayers to users of these screenings. Data Sources 2007–2013 Medicare Current Beneficiary Survey, Medicare FFS claims, and the Area Health Resource Files. Study Design Our sample included enrollees in FFS Part B for the entire calendar year. We excluded beneficiaries with a claims-documented or self-reported history of targeted cancers, or those enrolled in Medicaid or Medicare Advantage plans. We identified use of low-value Pap smears, mammograms, and prostate-specific antigen tests based on established algorithms, and estimated a logistic model with year dummies separately for each test. Data Collection/Extraction Methods Secondary data analyses. Principal Findings We found a statistically significant positive association between privileged socioeconomic characteristics and use of low-value screenings. Having higher income and supplemental private insurance strongly predicted more net subsidies from Medicare. Conclusions FFS enrollees who are better off in terms of sociodemographic characteristics receive greater subsidies from taxpayers for using low-value cancer screenings.
Enhancing Team Learning Participation: Creating Incentives through Bonus Adjustment Techniques

In an attempt to promote and gain wider acceptance of team learning activities in the classroom, researchers have recommended detailed incentive plans, ranging from controlling student behavior to instilling the fundamental values of cohort responsibility to emphasizing the benefits of lifelong learning. While such strategies may be useful, implementation can be cumbersome and uneconomical, and thus unpalatable to faculty. This paper offers a simple but effective participation incentive strategy. Students are more likely to participate in team activities if bonus scores are awarded. This model is an application of the labor supply theory and an extension of premium wages paid for overtime work. Incentives to work are enhanced as premium wages increase the opportunity costs of leisure. Data collected in ten introductory economics classes support the conclusion that awarding variable bonus scores will have a substantive effect on increasing participation.
Chronic low-back pain in adult with diabetes: NHANES 2009–2010

Abstract The aim of this study was to test the hypothesis that diabetes mellitus (DM) is associated with an increased prevalence of chronic low back pain (CLBP) in the general population. We analyzed data for 5106 adults (4591 without DM & 515 with diagnosed DM), who were part of the National Health and Nutrition Examination Survey (NHANES) from 2009 through 2010. Adults with DM were older (mean age 54.2years' vs. 42.1years), more likely to be obese (BMI>30, 69.5% vs. 33.3%), less educated (college or above 44.4% vs. 57.3%), had a lower annual income ( P =.050). After the adjustments for CLBP's known risk factors, the association remained significant (OR 1.39; 95% CI, 1.02–1.92, P =.041). Adults with DM have a higher prevalence of CLBP. Further research is needed to examine the association and pathophysiology of DM and CLBP as well as the role of shared risk factors. Summary Adults with diabetes have higher prevalence of chronic low back pain (CLBP), and higher odds of CLBP after adjusting for LBP risk factors.
What Are MOOCs

The large MOOC platforms were introduced against the background of the occupational and educational crises after 2008. The first Massive Open Online Courses, or MOOCs, were introduced in 2007 and entered the higher education scene and attracted immediate attention after the large platforms entered the scene after 2012. MOOCs had their origins in distance education, e-learning and open education. This chapter critically examines the meaning of the MOOC acronym, explains the vision and aims of the MOOC founders and charts the spread of MOOCs around the world and across the spectrum of learning situations after the launch of the big U.S. MOOC platforms.
Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

Abstract Background The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. Patients and Methods We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as “did no exercise” vs. “light, moderate, or vigorous exercise in ≥ 10-minute bouts”), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Results Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than “no exercise”. Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Conclusion Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death.
Risk, resilience, and complexity: Experiences of foster parents

Abstract Foster parents are the individuals who provide caregiving services to children in substitute care. Foster parents are faced with multiple demands when it comes to providing care for foster children, for which they may not expect or be prepared. The purpose of this study was to examine current and former foster parents' experiences within the child welfare system to better understand what their unique experiences have been and their perception of the need for changes to the system, specifically highlighting areas of resilience. This study included 39 current and former foster parents from across the United States. Three overarching themes were identified: concerns about the complexity of the child welfare system, personal narratives that highlight the complexity in the system, and means of navigating complex experiences within the child welfare system. Findings were described and discussed within the context of a resilience model. These findings have implications for foster parent training, support, and intervention with foster parents currently involved in the child welfare system.
Quasinormal modes of charged scalars around dilaton black holes in 2 + 1 dimensions: Exact frequencies

We have studied the charged scalar perturbation around a dilaton black hole in $2+1$ dimensions. The wave equations of a massless charged scalar field are shown to be exactly solvable in terms of hypergeometric functions. The quasinormal frequencies are computed exactly. The relation between the quasinormal frequencies and the charge of the black hole, charge of the scalar, and the temperature of the black hole are analyzed. The asymptotic form of the real part of the quasinormal frequencies is evaluated exactly.
Feasibility of a Lifestyle Redesign®-Inspired Intervention for Well Older Adults.

Objective We examined the feasibility of Aging Well by Design, a Lifestyle Redesign®-inspired intervention for community-dwelling older adults. The original Lifestyle Redesign program was shortened to 3 mo and implemented as a community outreach program of a major health care system. Method Community-dwelling older adults participated in the 12-wk program, which emphasized an occupational approach to healthy aging. Outcomes evaluated were recruitment, attendance, resource use, participant satisfaction, and subjective benefit to participants. Results The 13 participants, ages 66-88 yr, attended an average of 10 of 12 sessions. The intervention was completed as planned, physical resources were suitable, and financial resources were adequate. Participants expressed satisfaction with the program's facilitator, group discussions, and materials. Perceived benefits were social relationships, awareness of community resources, and change in attitude toward aging. Conclusion Implementation of a 3-mo Lifestyle Redesign-inspired program within a health care system was feasible.
Polymer-dispersed and encapsulated liquid crystal films

Thin polymer films containing microdroplets of liquid crystalline (LC) material are potentially use- ful for a variety of electro-optic applications because they can be switched electrically from a light scattering state to a transparent state.1-20 In this chapter, we shall describe the structure, opera- tion, and preparation of these films and review their electro-optic properties. Although electronic information displays are a very promising application of these films, we will not discuss topics such as full color capability19 or addressing schemes, which are unique to display applications. Rather, we shall emphasize those electro-optic characteristics which are important for control of solar radiation in buildings and automobiles; some of these, of course, are also important for display applications. We shall also restrict our discussion to films containing nematic LC droplets.
Fostering Interprofessional Education Through a Multidisciplinary, Community-Based Pandemic Mass Vaccination Exercise

We expanded health care services to economically disadvantaged individuals in an interprofessional, student-driven vaccination effort that also served as a pandemic planning drill. Health care professional students from colleges in and around Rockford, Illinois participated in implementing a mass vaccination event from 2011 to 2014 that targeted the underserved population. There was a 459% increase in total vaccinations administered to at-risk patients from year 1 to year 4. This interprofessional health care student–driven effort expanded medical service to disadvantaged individuals.
A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAFV600E-Mutant Brain Tumor

BRAFV600E hyperactivates ERK and signals as a RAF inhibitor-sensitive monomer. Although RAF inhibitors can produce impressive clinical responses in patients with mutant BRAF tumors, the mechanisms of resistance to these drugs are incompletely characterized. Here, we report a complete response followed by clinical progression in a patient with a BRAFV600E-mutant brain tumor treated with dabrafenib. Whole-exome sequencing revealed a secondary BRAFL514V mutation at progression that was not present in the pretreatment tumor. Expressing BRAFV600E/L514V induces ERK signaling, promotes RAF dimer formation, and is sufficient to confer resistance to dabrafenib. Newer RAF dimer inhibitors and an ERK inhibitor are effective against BRAFL514V-mediated resistance. Collectively, our results validate a novel biochemical mechanism of RAF inhibitor resistance mediated by a secondary mutation, emphasizing that, like driver mutations in cancer, the spectrum of mutations that drive resistance to targeted therapy are heterogeneous and perhaps emerge with a lineage-specific prevalence.Significance: In contrast to receptor tyrosine kinases, in which secondary mutations are often responsible for acquired resistance, second-site mutations in BRAF have not been validated in clinically acquired resistance to RAF inhibitors. We demonstrate a secondary mutation in BRAF (V600E/L514V) following progression on dabrafenib and confirm functionally that this mutation is responsible for resistance. Cancer Discov; 8(9); 1130-41. ©2018 AACR.See related commentary by Romano and Kwong, p. 1064This article is highlighted in the In This Issue feature, p. 1047.
D. Ray Fulkerson

Ray Fulkerson’s seminal work in network flows, large-scale linear programming (LP), combinatorial optimization, and combinatorics has had an enormous influence on the practice of Operations Research (OR). His seminal book, Flows in Networks, co-written with Lester R. Ford, Jr., was instrumental in bringing network flow theory and algorithms to the domain of OR practice—in communications, transportation, supply systems—and in hastening the development of academic courses in networks, graph theory, and combinatorics. Much of his most influential work began with an application, a puzzle, or a specific computational obstacle. Pursuit of the underlying mathematical structures led Ray and his collaborators to broad and profound methodological innovations, such as cutting planes and column generation, and to the foundations of network flow theory and polyhedral combinatorics.
Knowledge-based methods for evaluation of engineering changes

Engineering Changes (ECs) are an integral part of a product's lifecycle. A proposed EC can affect several lifecycle-wide components. Detailed evaluation of each proposed EC or its effect is time-consuming and inefficient. Therefore, enterprises plan detailed evaluation of only those EC effects that might have a high cost impact. Currently, domain experts decide which effects should undergo a detailed evaluation process. Such an approach relies heavily on personal experience and is less reliable. To address this problem, this research develops a systematic knowledge-based method for determining whether a proposed EC effect has high impact and would require a detailed evaluation. Only some of the large number of EC attributes are important for retrieving past ECs, which can be used to evaluate the impact of a proposed EC. This research formulates the problem of determining important EC attributes as a multi-objective optimization problem. Information-theoretic concepts are used to define measures for quantifying importance of an attribute subset. The domain knowledge and the information in EC database are combined to estimate probability distributions, which are required in computation of measures. An Ant Colony Optimization (ACO)-based search approach is developed for efficiently locating the important attribute set. Utilizing past EC knowledge to predict the impact of proposed EC effect requires an approach to compute similarity between ECs. The second part of this research presents an approach to compute similarity between ECs that are defined using disparate attributes. Since the available information is probabilistic, the measures of information are utilized for defining measures to compute similarity between two attribute values or ECs. The semantics associated with attribute values are utilized to compute similarity between attribute values. In the last part of this research, an approach is developed to predict impact of proposed EC effect based on the similar past ECs. The approach incorporates a technique to quantify differences between important attribute values in proposed EC and a similar past EC. The Bayes's rule is used to determine differences in impact value from the differences in attribute values. The probability values required in the Bayes's rule are determined based on the minimum cross entropy principle.
Identification of Equivalent Linear Systems

Civil engineering structures are designed, analyzed and constructed in order to fulfil specific needs and they are expected to perform their functions accordingly. However, civil engineering structures are subjected to random disturbances which may result in a random system performance. Furthermore, dynamic characteristics such as mass, stiffness and damping, used for design and analysis, involve idealization, approximation and uncertainty to the extent that their performance even under prescribed disturbances must be considered non-deterministic.
Abstract 1553: Carcinoembryonic antigen (CEA) expression is regulated by mutant KAS in mucinous colon cancers

Purpose: Carcinoembryonic antigen (CEA/CEACAM5) is a marker and prognostic indicator for colorectal cancers (CRCs). CEA overexpression is also a major causative factor in the development of liver metastasis from a significant fraction of colorectal cancers (CRC) including mucinous adenocarcinomas (MCAs). Very little is known about the molecular mechanisms that regulate the expression of CEA in cancers in general and in CRCs in particular. This study tests the hypothesis that mutant KRAS, a frequently mutated gene in CRCs, regulates CEA expression in CRCs. Methods: Mutant KRAS expression was reduced in two high CEA-expressing mucinous CRC cell lines, LS174T (KRAS G12D) and RW7213 (KRAS G12C), by short hairpin RNA (shRNA)-mediated knockdown using a lentiviral vector. Inducible and reversible knockdown of KRAS was achieved by addition or withdrawal of doxycycline. Alterations in activation of ERK-and PI3K-pathway effectors downstream of KRAS were assessed by Western blots. Two small-molecule inhibitors, pictilisib (GDC0941) and cobimetinib (GDC0973), were used to inhibit PI3K and MEK respectively. Results: Knockdown of mutant KRAS in CRC cell lines reduced CEA expression. However, knockdown of wild-type RAS did not change CEA expression. Restoration of mutant KRAS reestablished CEA expression in both cell lines. This recovery of CEA expression was blocked by addition of the MEK inhibitor, cobimetinib or the PI3K inhibitor, picstilisib. Combined treatment with both inhibitors was more effective in reducing CEA expression than single-agent treatment. Conclusions: Our results suggest that mutant KRAS, through engagement of MEK-ERK and PI3K-AKT signaling pathways, regulates CEA expression in CRCs. CEA has been implicated in the development of lung and liver metastasis from CRCs, by reacting with stromal cells and altering the tumor microenvironment. Our results therefore, suggest a potential vulnerability that could be exploited for antimetastatic therapy. Citation Format: Murali Kuracha, Venkatesh Govindarajan, Brian W. Loggie, Peter Thomas. Carcinoembryonic antigen (CEA) expression is regulated by mutant KAS in mucinous colon cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1553.
Inside Job: Exploring the Connection Between Whistleblowing and Perceptions of Procedural Justice

Recent instances of whistleblowing by U.S. federal employees have reinvigorated scholarly interest in its role toward ethical administration. Previous studies have expanded our understanding of how...
Cultural inertia, identity, and intergroup dynamics in a changing context

Abstract Identity is a central component of social behavior. The theory of cultural inertia is used to address current research on identity in a changing context. The changing context provides new insights on identity and consequently new challenges for researchers in social psychology. The theory of cultural inertia borrows from the laws of motion and hypothesizes that stable groups resist change, whereas groups in motion continue changing at a steady rate. There are multiple psychological anchors and propellers that either produce further resistance to change or move cultures toward more change. Change produces conflicts that result in intergroup tensions. The cultural inertia model is used to organize data, to make new predictions, and to understand current social and political phenomena.
The paradox of border security – an example from the UK

Abstract The study of borders has experienced a renaissance in various disciplines, but the concept of vernacular security in the field of borders and the politics that surround them has been neglected. This article uses a people approach and examines the perceptions and understandings of the UK civil society and ‘their’ state border. Using the example of the UK is particularly interesting because governments have invested high efforts into constructing a more stringent, efficient and secure UK border for decades. As consequence, the concept of border has gained a raised public profile in the UK, which questions security perceptions by members of the UK civil society and what the UK border means to them. Drawing on a variety of empirical data and employing critical discourse analysis, this article will show an ambiguous and paradoxical picture of the UK border instead of its usually assumed monolithic symbolism of security and protection. The article shows that there is a mismatch present in border politics: security is aimed at however insecurity is generated. This mismatch and confusion among members of the UK civil society have further political and societal consequences. Borders and bordering effectively insecuritize people by which, as the article argues, the concept of vernacular security moves to the forefront of new theorizations of the relationship between borders, security and politics.
Telephone Companies Have First Amendment Rights Too: The Constitutional Case for Entry into Cable

This Article addresses what in some respects is the most disappointing aspect of the debate, the relegation of constitutional principles to secondary or tertiary status. It may seem strange to stress the first amendment rights of the "big, bad telephone companies," especially since freedom of expression is too often associated only with that of individuals or the established media. But the first amendment fundamentally concerns our common interest in assuring freedom of expression to all, not just officially preferred, speakers. Thus, the challenge is to begin from the premise that telephone companies have a right to develop, own, and operate cable systems. Government should allow their participation in the media without infringing their first amendment freedoms or stifling technological progress, while taking appropriate steps to avoid possible excesses. Part II of this Article surveys the FCC rules, statutory provisions, and court decrees that constitute the ban on telephone companies entering the cable business and the justifications offered for it. Part III begins the constitutional analysis by demonstrating that the telcos' first amendment rights are not qualified by their corporate nature, their common carrier status, or other existing media cross-ownership restrictions. Part IV first considers the proper relationship between antitrust and first amendment principles and then establishes that the ban should be treated as a prior restraint. Finally, Part V considers briefly the possible technological benefits from telco entry into cable which may be jeopardized by continuation of the ban.
Locus coeruleus toggles reciprocal prefrontal firing to reinstate fear

The medial prefrontal cortex (mPFC) plays an essential role in regulating emotion, including inhibiting fear when danger has passed. The extinction of fear, however, is labile and a number of factors, including stress, cause extinguished fear to relapse. Here we show that fear relapse in rats limits single-unit activity among infralimbic (IL) neurons, which are critical for inhibiting fear responses, and facilitates activity in prelimbic (PL) neurons involved in fear expression. Pharmacogenetic activation of noradrenergic neurons in the locus coeruleus mimics this shift in reciprocal IL-PL spike firing, increases the expression of conditioned freezing behavior, and causes relapse of extinguished fear. Noradrenergic modulation of mPFC firing represents a mechanism for relapse and a potential target for therapeutic interventions to reduce pathological fear.
Efficient Synthesis of Clofarabine and Gemcitabine from 2-Deoxyribonolactone.

New syntheses of clofarabine (VI) and gemcitabine (X) based on a previously described electrophilic fluorination method for the synthesis of 2-fluoro furanose derivatives are described.
How neutrinos get mass and what other things may happen besides oscillations

In this talk I address the theoretical issue of why new physics is required to obtain a nonzero neutrino mass. I then discuss what other things may happen besides neutrino oscillations. In particular I consider a possible new scenario of leptogenesis in R-parity nonconserving supersymmetry.
Lawyers and Jurors: Interrogating Voir Dire Strategies by Analyzing Conversations

This study of individualized jury selection for 792 potential jurors across 12 North Carolina capital cases, selected with purposive case selection, analyzes the conversations that occur during voir dire to examine the process that produces decisions about who serves on juries. Lawyers question prospective jurors in voir dire partly to gather information about prospective jurors’ ability to decide a case without prejudice. Jury selection, however, suffers from what social scientists call demand characteristics. Demand characteristics provide a respondent with clues about the expected response and interfere with effective information gathering. We identified two characteristics that bear on the presence and strength of demand characteristics: the form and tone of the question. We sorted all 8,583 general legal opinion questions along a four‐step scale by combining these characteristics. We then used time‐series analyses to examine responses to these questions in sequence. Juror responses were longest and most likely to include an affective utterance when the demand characteristics were weaker, and that loquaciousness and affect fell at each step of the scale. An independent qualitative study replicated these findings, and supported the assertion that length and form are valid measures of quality in this context.
Human–Water Infrastructure Interactions: Substituting Services Received for Bottled and Filtered Water in US Shrinking Cities

AbstractAging infrastructure has caused municipalities to experience an increasing number of water-related challenges, such as noncompliance with water-quality standards or failing infrastructure. ...
Outcomes After Cervical Disc Arthroplasty Versus Stand-Alone Anterior Cervical Discectomy and Fusion: A Meta-Analysis.

Study Design:Systemic review and meta-analysis.Objectives:To review and compare surgical outcomes for patients undergoing stand-alone anterior cervical discectomy and fusion (ACDF) versus cervical ...