cssi/SciSciGPT-SciSciNet huggingface dataset:
Acetylation of WRN protein regulates its stability by inhibiting ubiquitination

Background WRN is a multi-functional protein involving DNA replication, recombination and repair. WRN acetylation has been demonstrated playing an important role in response to DNA damage. We previously found that WRN acetylation can regulate its enzymatic activities and nuclear distribution.
Kinetic Dependence Graphs

Task graphs or dependence graphs are used in runtime systems to schedule tasks for parallel execution. In problem domains such as dense linear algebra and signal processing, dependence graphs can be generated from a program by static analysis. However, in emerging problem domains such as graph analytics, the set of tasks and dependences between tasks in a program are complex functions of runtime values and cannot be determined statically. In this paper, we introduce a novel approach for exploiting parallelism in such programs. This approach is based on a data structure called the kinetic dependence graph (KDG), which consists of a dependence graph together with update rules that incrementally update the graph to reflect changes in the dependence structure whenever a task is completed. We have implemented a simple programming model that allows programmers to write these applications at a high level of abstraction, and a runtime within the Galois system [15] that builds the KDG automatically and executes the program in parallel. On a suite of programs that are difficult to parallelize otherwise, we have obtained speedups of up to 33 on 40 cores, out-performing third-party implementations in many cases.
Mammary gland development is mediated by both stromal and epithelial progesterone receptors.

A combination of a knockout mouse model, tissue transplantation, and gene expression analysis has been used to investigate the role of steroid hormones in mammary gland development. Mouse mammary gland development was examined in progesterone receptor knockout (PRKO) mice using reciprocal transplantation experiments to investigate the effects of the stromal and epithelial PRs on ductal and lobuloalveolar development. The absence of PR in transplanted donor epithelium, but not in recipient stroma, prevented normal lobuloalveolar development in response to estrogen (E) and progesterone (P) treatment. Conversely, the presence of PR in the transplanted donor epithelium, but not in the recipient stroma, revealed that PR in the stroma may be necessary for ductal development. Members of the Wnt growth factor family, Wnt-2 and Wnt-5B, were employed as molecular markers of steroid hormone action in the mammary gland stroma and epithelium, respectively, to investigate the systemic effects of E and P. Hormonal treat...
Parametric Doppler Spread Estimation in Mobile Fading Channels

In this work, a parametric method is proposed to estimate the Doppler spread, or the mobile speed by modeling the received data as an autoregressive process. The method can be extended to a spatial-temporal parametric Doppler spread estimator when multiple antennas are available at the receiver. Compared to the nonparametric estimator based on periodogram method, the parametric estimator can achieve a higher resolution, providing more accurate mobile speed information without increasing the computation complexity.
Theoretical aspects of antibiotic diffusion into microbial biofilms.

Antibiotic penetration into microbial biofilm was investigated theoretically by the solution of mathematical equations describing various combinations of the processes of diffusion, sorption, and reaction. Unsteady material balances on the antibiotic and on a reactive or sorptive biomass constituent, along with associated boundary and initial conditions, constitute the mathematical formulations. Five cases were examined: diffusion of a noninteracting solute; diffusion of a reversibly sorbing, nonreacting solute; diffusion of an irreversibly sorbing, nonreacting solute; diffusion of a stoichiometrically reacting solute; and diffusion of a catalytically reacting solute. A noninteracting solute was predicted to penetrate biofilms of up to 1 mm in thickness relatively quickly, within a matter of seconds or minutes. In the case of a solute that does not sorb or react in the biofilm, therefore, the diffusion barrier is not nearly large enough to account for the reduced susceptibility of biofilms to antibiotics. Reversible and irreversible sorption retards antibiotic penetration. On the basis of data available in the literature at this point, the extent of retardation of antibiotic diffusion due to sorption does not appear to be sufficient to account for reduced biofilm susceptibility. A catalytic (e.g., enzymatic) reaction, provided it is sufficiently rapid, can lead to severe antibiotic penetration failure. For example, calculation of beta-lactam penetration indicated that the reaction-diffusion mechanism may be a viable explanation for failure of certain of these agents to control biofilm infections. The theory presented in this study provides a framework for the design and analysis of experiments to test these mechanisms of reduced biofilm susceptibility to antibiotics.
Spatial Damage Distribution in Electron-Beam Processed Gaas-Algaas Heterostructures, Experiment and Theory

The effect of electron beam irradiation on the transport properties of HEMT structures has been studied. The data is found to agree with a model containing no free parameters which predicts the spatial extent of the damage. As grown HEMT material was fabricated into Hall bars. The material was then characterized by measurement of 2D EG number density and drift mobility. The material was then irradiated at constant dose with electron energies between 2.5 and 20 keV. Damage was assessed by changes in the number density and mobility. The number density was essentially unchanged at all energies. No change in mobility occurred for 2.5, 15, and 20 keV, however, a decrease in the mobility occurred for energies from 5.0 to 12.5 keV. These results agree with our model of the electrons energy loss as a function of its path length. The defects are shown to be charged, and possible sources of the defects are discussed.
Emotional Behavior of the White Rat Following Full-Thickness Thermal Burns

(1963). Emotional Behavior of the White Rat Following Full-Thickness Thermal Burns. The Journal of Psychology: Vol. 56, No. 2, pp. 375-384.
Structural and spectroscopic models of the A-cluster of acetyl coenzyme a synthase/carbon monoxide dehydrogenase: Nature's Monsanto acetic acid catalyst

Acetyl coenzyme A synthase/carbon monoxide dehydrogenase (ACS/CODH) is a bifunctional enzyme present in a number of anaerobic bacteria. The enzyme catalyzes two separate reactions namely, the reduction of atmospheric CO2 to CO (CODH activity at the C-cluster) and the synthesis of acetyl coenzyme A (ACS activity at the A-cluster) from CO, CH3 from a corrinoid iron-sulfur protein, and the thiol coenzyme A. The structure(s) of the A-cluster of ACS/CODH from Moorella thermoacetica revealed an unprecedented structure with three different metallic subunits linked to each other through bridging Cys-S residues comprising the active site. In these structure(s) a Fe 4S4 cubane is bridged via Cys-S to a bimetallic metal cluster. This bimetallic cluster contains a four-coordinate Ni, Cu, or Zn as the proximal metal (to the Fe4S4 cluster; designated Mp), which in turn is bridged through two Cys-S residues to a terminal square planar Ni(II) (Ni d, distal to Fe4S4) ligated by two deprotonated carboxamido nitrogens from the peptide backbone. It is now established that Ni is required at the Mp site for the ACS activity. Over the past several years modeling efforts by several groups have provided clues towards understanding the intrinsic properties of the unique site in ACS. To date most studies have focused on dinuclear compounds that model the Mp–Nid subsite. Synthesis of such models have revealed that the Nip sites (a) are readily removed when mixed with 1,10-phenanthroline (phen) and (b) can be reduced to the Ni(I) and/or Ni(0) oxidation state (deduced by EPR or electrochemical studies) and bind CO in terminal fashion with νco value similar to the enzyme. In contrast, the presence of Cu(I) centers at these M p sites do not bind CO and are not removable with phen supporting a non-catalytic role for Cu(I) at the Mp site in the enzyme. The Nid site (coordinated by carboxamido-N/thiolato-S) in these models are very stable in the +2 oxidation state and not readily removed upon treatment with phen suggesting that the source of ‘labile Ni’ and the NiFeC
PROGRAMMING UNDER UNCERTAINTY: THE COMPLETE PROBLEM

We define the complete problem of a two-stage linear programming under uncertainty, to be: $$\begin{gathered} Minimize z(x) = E_\xi \{ cx + q^ + y^ + + q^ - y^ - \} \hfill \\ subject to Ax = b \hfill \\ Tx + Iy^ + + Iy^ - = \xi \hfill \\ x \geqq 0,y^ + \geqq 0,y^ - \geqq 0 \hfill \\ \end{gathered} $$ where x is the first-stage decision variable, the pair (y+, y−) represents the second-stage decision variables. In order to solve this class of problem, we derive a convex programming problem, whose set of optimal solutions is identical to the set of optimal solutions of our original problem. This problem is called the equivalent convex programming. If the random variable ξ has a continuous distribution, we give an algorithm to solve the equivalent convex program. Moreover, we derive explicitly the equivalent convex program for a few common distributions.
Pulse-width modulated drive for high performance DC motors

A detailed study is presented of pulse width-modulated (PWM) motor drives for the purpose of determining their characteristic and providing accurate implementation and computer simulation procedures. Depending on the configuration of the drive circuit, the motor can be driven in any of several modes, resulting in either a linear or nonlinear characteristic. These modes of operation have been analyzed and tested in the laboratory. Modeling and simulation have also been performed and results are presented for comparison with experimental counterparts. >
THE NEW OTHER VICTORIANS: THE SUCCESS (AND FAILURE) OF QUEER THEORY IN NINETEENTH-CENTURY BRITISH STUDIES

Much of the critical writing on Queer Theory and Sexuality Studies in a Victorian context over the last decade or so has been absorbing, exploring, complicating, and working under the burden of the influence of Michel Foucault's theoretical writings on erotic relations and identity. The first volume of Foucault's The History of Sexuality (1978), in fact, had begun with a gauntlet thrown down before Victorian Studies, a chapter-long critique of Steven Marcus's The Other Victorians (1966), a work that had offered an entirely new and at the time, quite bold avenue of exploring nineteenth-century culture – namely, through the pornographic imagination that Marcus taxonomized with precise, clinical flair as a “pornotopia” in which “all men . . . are always infinitely potent; all women fecundate with lust and flow inexhaustibly with sap or both. Everyone is always ready for everything” (276). In Foucault's telling, however, Marcus demonstrated a theoretically impoverished faith in Freudian models of “repression” in Marcus's examination of “underground” Victorian sexualities. It was Marcus's reliance on the “repressive fallacy,” his conviction that there existed a demarcated spatial and psychic Victorian counter-world that The History of Sexuality had so forcefully undermined.
Superconducting resonator as beam-induced signal pickup

The first demonstration of a superconducting resonator (SCR), installed for beam acceleration, to detect the arrival time of a beam bunch is described. The detecting resonator is operated at very low field level, comparable to the field induced by the beam pulse traversing the cavity so as to maintain an acceptable response characteristic for this high-Q device. Due to this, the RF field in an SCR is always a superposition of a "pure" (or reference) RF and the beam-induced signal. A new method of circular phase rotation (CPR), allowing extraction of the beam phase information from the composite RF field was developed. Arrival time phase determination with CPR is better than one degree for a beam current of 100 nA. The electronics design is described and example data are presented.
Integrin α4β1 Is Necessary for CD4+ T Cell–Mediated Protection against Genital Chlamydia trachomatis Infection

Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection in the United States and a significant health burden worldwide. Protection from Chlamydia infection in the genital mucosa is dependent on IFN-γ derived from CD4 + Th1 cells. These CD4 + T cells must home successfully to the genital tract to exert their effector function and decrease C. trachomatis burden. Although adhesion receptors expressed by CD4 + T cells in the genital tract have been characterized, the integrin receptor required for Chlamydia -specific CD4 + T cell–mediated protection has not been explored. In this study, we demonstrate that C. trachomatis infection of the upper genital tract results in recruitment of Chlamydia -specific CD4 + T cells robustly expressing the integrin α 4 β 1 . Interfering with α 4 β 1 , but not α 4 β 7 , function resulted in defective CD4 + T cell trafficking to the uterus and high bacterial load. We conclude that integrin α 4 β 1 is necessary for CD4 + T cell–mediated protection against C. trachomatis infection in the genital mucosa. By identifying homing molecules required for successful CD4 + T cell trafficking to C. trachomatis –infected tissues, we will be better equipped to design vaccines that elicit sterilizing, long-lasting immunity without inducing immune pathologies in the upper genital tract.
ANENCEPHALUS, DRINKING WATER, GEOMAGNETISM AND COSMIC RADIATION

The mortality rates from anencephalus from 1950-1969 in Canadian cities are shown to be strongly correlated with city growth rate and with horizontal geomagnetic flux, which is directly related to the intensity of cosmic radiation. They are also shown to have some association with the magnesium content of drinking water. Prior work with these data which showed associations with magnesium in drinking water, mean income, latitude and longitude was found to be inadequate because it dismissed the observed geographic associations as having little biological meaning, and because the important variables of geomagnetism and city growth rate were overlooked.
The Obesity Epidemic and Consequences for Rheumatoid Arthritis Care

With the prevalence of obesity increasing dramatically worldwide over the past several decades, an increasing body of literature has examined the impact of obesity in the context of rheumatoid arthritis (RA). Epidemiologic studies suggest that obesity may be associated with a modestly increased risk for the development of RA, although these studies have shown conflicting results. Among patients with established RA, obesity has been observed to be associated with greater subjective measures of disease activity and poor treatment response, but also with a decreased risk of joint damage and lower mortality. A comprehensive evaluation of the influence of obesity on the measurement of disease, response to therapies, and long-term prognosis is critical in order to understand these observations. This review therefore focuses on recent observations, potential explanations for these findings, and implications for clinicians and investigators caring for and studying patients with RA.
Outlier ensembles

Ensemble analysis is a widely used meta-algorithm for many data mining problems such as classification and clustering. Numerous ensemble-based algorithms have been proposed in the literature for these problems. Compared to the clustering and classification problems, ensemble analysis has been studied in a limited way in the outlier detection literature. In some cases, ensemble analysis techniques have been implicitly used by many outlier analysis algorithms, but the approach is often buried deep into the algorithm and not formally recognized as a general-purpose meta-algorithm. This is in spite of the fact that this problem is rather important in the context of outlier analysis. This talk discusses the various methods which are used in the literature for outlier ensembles and the general principles by which such analysis can be made more effective. A discussion is also provided on how outlier ensembles relate to the ensemble-techniques used commonly for other data mining problems.
MIP Model for Inventory Routing in Industrial Gases Supply Chain

A mixed-integer programming (MIP) model is developed to address inventory routing in industrial gases supply chains. First, we propose a discrete-time approach to address the basic problem, with bo...
Primary role of cytochrome P450 2B6 in the oxidative metabolism of 2,2′,4,4′,6-pentabromodiphenyl ether (BDE-100) to hydroxylated BDEs

Human exposure to polybrominated diphenyl ethers (PBDEs) through various routes poses deleterious health effects. PBDEs are biotransformed into hydroxylated metabolites (OH-BDEs) via cytochrome P45...
A phase I study of methotrexate administration following 5-fluorouracil.

A priming dose of 5-fluorouracil can decrease the toxicity and retain the efficacy of high-dose methotrexate in laboratory models. This Phase I study determined the maximum tolerated dose of methotrexate that can be administered after a dose of 5-fluorouracil without leucovorin rescue. Forty-two patients received 5-fluorouracil (500 mg/m 2 ) by bolus injection followed in 2 h by methotrexate infused over 1 h ; treatment was repeated every 3 weeks. Patients received five doses ofleucovorin (10 mg/m 2 every 6 h) ; this was reduced to two doses and then to zero doses (no rescue) if less than grade 2 toxicity occurred in prior treatments. If safe, at least two patients received no leucovorin rescue with their first treatment. The dose of methotrexate was escalated in cohorts of patients, starting with a methotrexate dose of 200 mg/m 2 . Previously untreated patients maximally tolerated 1600 mg/m 2 of methotrexate with 5-fluorouracil pretreatment. Leukopenia combined with stomatitis prevented deescalation ofleucovorin doses. Fourteen percent of total courses and 15% of courses without leucovorin rescue resulted in dose limiting toxicity. MTX levels exceeded levels that require leucovorin rescue. Four of the 33 (12%) advanced head and neck cancer patients had objective responses to therapy ; median survival was 10 months. Previously treated patients were less tolerant ; oral and hematological toxicities were troublesome ; 400 mg/m 2 of methotrexate was the approximate maximum tolerated dose. Forty-seven percent oftotal courses and 60% ofcourses without leucovorin rescue resulted in dose limiting toxicity. There were no responses. Although the antineoplastic activity is poor, prior 5-fluorouracil exposure does protect tissues susceptible to methotrexate toxicity.
Magnesium deficiency enhances basal glucose disposal in the rat.

To investigate the contribution of hepatic and peripheral tissues to the enhanced glucose disposal rate (Kg) observed in magnesium (Mg)-deficient rats, euglycemic-hyperinsulinemic clamps were performed with continuous infusion of [3-3H]glucose and three insulin infusion rates, 1, 8, and 16 microU.kg-1.min-1. Moderately Mg-deficient (Mg-, 4.2 microM Mg/g diet) and Mg-adequate (Mg+, 16.7 microM Mg/g diet) Sprague-Dawley rats were studied after 3 wk of dietary treatment. Growth, fasting glucose, and insulin concentrations were not affected by dietary treatment. Basal hepatic glucose output (HGO) and glucose disposal (Rd) were increased by 24% in Mg- rats (P < 0.001). After 1 microU insulin.kg-1.min-1 infusion, Rd and the glucose infusion rate that maintained euglycemia were significantly increased in Mg- rats by 24 and 46%, respectively. However, when the increase in Rd above baseline was examined, no significant differences were observed. Therefore, the increased basal glucose disposal observed in Mg- rats may be mediated by noninsulin-dependent mechanisms. Insulin suppression of HGO during 1 microU insulin.kg-1.min-1 infusion was greater in Mg- rats (43%) compared with Mg+ rats (27%, P < 0.05). In conclusion, the increased Kg observed in Mg- rats is likely to be caused by an increase in noninsulin-mediated glucose uptake and an enhancement of hepatic insulin sensitivity.
Paper Electrophoretic Study of G14 Fat Emulsion Cleared from Post-Heparin Rat Plasma:

SummaryC14-labeled fat emulsion was incubated with post-heparin plasma and the mixture was then subjected to filter paper electrophoresis. Some of the C14 activity was found to migrate with the albumin fraction.
A MODEL OF KIN-STRUCTURED MIGRATION.

When individuals disperse from one local group to another, they often do so in the company of relatives. This is known as "kin-structured migration," and its effect on genetic population structure is investigated here. It is shown that when migration is kin-structured, the ratio of between- to within-group variance is increased by a quantity that can be estimated either from behavioral or genetic data. Theoretical results indicate that kin-structured migration should be most important in populations with high mobility, and analysis of data for humans and lions suggests the kin-structured migration may have a substantial effect on genetic population structure in both species. Its effect seems to be small in a population of pine voles.
Student Achievement in an Introductory Biology Course: Assessing Grade Motivation and Study Log Metacognition

As college educators, our main teaching goals are to increase student learning and improve student retention. This study describes how 54 science majors at a public, minority serv- ing institution reflected on their study time, study activities, and overall grade motivation in a core-curriculum introduc- tory biology course. Since 2005, less than 50% of students enrolled in this course at our university earned a final grade of “C” or better. In the Fall semester of 2009, we adminis- tered a pre and post assessment using the Science Motivation Questionnaire (SMQ) a 30-item Likert-type instrument devel- oped by Glynn and Koballa (2006) to better understand and address the student attrition from the introductory biology course. All 30 items from the SMQ were analyzed, but only 5 items relevant to grade motivation are presented in this paper. We also designed and implemented a weekly study log assessment tool for students to document their study time and study activities, wherein students submitted their study logs on a weekly basis during the course of this research study. Based on the number of study logs submitted and study time by each student, students were classified into ei- ther a high-metacognition or low-metacognition group. For our purposes, we defined metacognition as the awareness of one’s own thinking process (Merriam-Webster, 2012). The high-metacognition group submitted 75% of their study logs and earned a grade in the top 25% of the class. The low- metacognition group submitted only 25% of their study logs and earned a grade in the bottom 25% of the class. Thus both groups formed reasonable expectations for their overall class performance.
A Predictive Model for Cereal Leaf Beetle Mortality from Sub-freezing Temperatures

A predictive model is developed relating mortality of adult cereal leaf beetles ( Oulema melanopus , L.) to the duration and severity of continuous cold exposures. Experiments reveal the importance of a seasonal change in cold tolerance, preconditioning, and recovery from successive cold exposures in determining mortality from exposures of the type encountered in the field.
The Internet and Autocracy: Unpacking the Effects of Internet Freedom

Previous work has demonstrated the importance of entrepreneurship and economic freedom in encouraging economic growth. However, the conditions under which societies tend to liberalize their economies toward business friendly environments have yet to be established and therefore merit further study. Using cross-sectional, time-series data, this paper finds a robust, positive relationship between Internet usage and the ease of doing business within countries. Moreover, this effect is particularly strong in countries with lower levels of democracy. Because the relationship between Internet usage and the ease of doing business is dynamic and theoretically endogenous, a Difference GMM approach is used to isolate the exogenous effects of Internet use by businesses. Given the increasing prevalence of information and communication technologies (ICTs) throughout the world, a robust relationship between Internet use and the ease of doing business suggests that the ease of doing business will continue to improve in the future.
The Didactic Contract, A Handshake and a Compromise

Having understood the role of negative affect in blocking student access to their own, as she would put, excellence, Prabhu et al. started the process of Creative Learning Environment design through several routes. First, she deconstructed concept of didactic contract to eliminate the ambiguity present in the term it acquired since the important work of Brusseau.
At the Origins of Modern Geography. The Oecumene: an Anthropogeographical Pattern

ABSTRACTGeography must be conceived in relation to man. It is not merely a description of the Earth, rather it accounts for the history of man’s relationship with it, of man’s movements on its surface, and his transformative impact on the world. From this perspective, Friedrich Ratzel was extraordinarily innovative respect to other nineteenth century scholars. That said, however, his revolutionary approach actually relied on an ancient foundation. To understand the basis of Ratzel’s anthropogeographical project it is vital to return to a Greek concept that, over the centuries, has been variously resemantized: the concept of the oecumene. In his understanding of the oecumene, the entire breadth of humanity is conceived in historical and geographical relation to the world around it. Ratzel’s anthropogeography aspires to an all-encompassing understanding of man. In fact, it allows us to reconstruct the coordinates of time and space through which man has developed as a being capable of culture. The Earth, acc...
Active metamaterials: A novel approach to manipulate terahertz waves

Compared to the neighboring infrared and microwave regimes, the terahertz (1 THz = 1012 Hz) regime is still in need of fundamental technological advances. This derives, in part, from a paucity of naturally occurring materials with useful electronic or photonic properties at terahertz frequencies. This results in formidable challenges in the generation, detection, and creation of devices to efficiently control and manipulate THz waves. Considering the promising potential applications of THz radiation, we need to overcome such material obstacles by actively searching for new materials, or by constructing artificial materials with a desired electromagnetic response. Metamaterials are a new type of artificial composite with electromagnetic properties that derive from their sub-wavelength structure. The potential of metamaterials for THz applications originates from their resonant electromagnetic response, which significantly enhances their interaction with THz radiation. Thus, metamaterials offer a route towards helping to fill the so-called "THz gap". In this work we design a series of novel planar THz metamaterials. Importantly, the critical dependence of the resonant response on the supporting substrate enables the creation of active THz metamaterials. We show that the resonant response can be efficiently controlled using optical or electrical approaches. This has resulted in the invention of efficient THz switches and modulators which will be of importance for advancing numerous real world THz applications.
Bipartite matching generalizations for peptide identification in tandem mass spectrometry

Motivation: Identification of spectra produced by a shotgun proteomics mass spectrometry experiment is commonly performed by searching the observed spectra against a peptide database. The heart of this search procedure is a score function that evaluates the quality of a hypothesized match between an observed spectrum and a theoretical spectrum corresponding to a particular peptide sequence. Accordingly, the success of a spectrum analysis pipeline depends critically upon this peptide-spectrum score function. Results: We developed peptide-spectrum score functions that compute the maximum value of a submodular function under m matroid constraints. We call this procedure a submodular generalized matching (SGM) since it generalizes bipartite matching. We use a greedy algorithm to compute maximization, which can achieve a solution whose objective is guaranteed to be at least 1/1+m of the true optimum. The advantage of the SGM framework is that known long-range properties of experimental spectra can be modeled by designing suitable submodular functions and matroid constraints. Experiments on four data sets from various organisms and mass spectrometry platforms show that the SGM approach leads to significantly improved performance compared to several state-of-the-art methods. Supplementary information, C++ source code, and data sets can be found at https://melodi-lab.github.io/SGM.
Abstract 2685: Paracrine effect of NRG1 and HGF drives resistance to MEK inhibitors in metastatic uveal melanoma

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Metastatic uveal melanoma (UM) patients usually die within one year, emphasizing an urgent need to develop new treatment strategies. Mitogen-activated protein kinase kinase (MEK) small molecule inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in UM patients. In this study, we identified compensatory mechanisms that provide resistance to MEK inhibition in metastatic UM. We screened for growth factors that were able to induce resistance in three newly characterized metastatic UM cell lines to MEK inhibitors, trametinib and selumetinib, with colony formation assay and viability assay. Cellular signaling pathway analysis was carried out to determine the molecular mechanisms of resistance to MEK inhibition in metastatic UM cells. Clinical-grade antibody and inhibitors targeting these pathways were used to determine their capability to overcome the resistance mediated by these growth factors. Conditioned medium collected from fibroblasts were used to evaluate whether stromal effect from fibroblasts could drive resistance to metastatic UM cells. We demonstrate that Neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1, whereas HGF induces sustained activation of AKT in the presence of trametinib. Individually targeting ERBB3 and cMET, the receptors for NRG1 and HGF, overcomes resistance to trametinib provided by these growth factors and by conditioned medium from fibroblasts, which produce NRG1 and HGF. Analysis of metastatic liver biopsies showed that ERBB2, which is the co-receptor for NRG1, and cMET were phosphorylated in some of these clinical specimens. Our data suggest that combination of MEK inhibitors with ERBB3 and cMET targeting agents may provide novel and effective treatment strategies in metastatic UM. Citation Format: Hanyin Cheng, Mizue Terai, Takami Sato, Andrew Aplin. Paracrine effect of NRG1 and HGF drives resistance to MEK inhibitors in metastatic uveal melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2685. doi:10.1158/1538-7445.AM2015-2685
Distortion product otoacoustic emissions in young adult and geriatric cats.

Recordings of distortion product otoacoustic emissions (DPOAEs) were taken from 15 geriatric cats (mean age ± standard deviation, SD, 13.6 ± 2.7 years; range 10.2-19.4 years) and 12 young adult control cats (mean ± SD 4.6 ± 0.5 years; range 3.4-5 years) to identify frequency-specific age-related changes in cochlear responses. Recordings were performed for primary frequencies from 2 to 12 kHz in 2 kHz increments. Cats were considered to be geriatric > 11.9 ± 1.9 years of age. Brainstem auditory evoked response (BAER) recordings were also made for subjective comparison with DPOAE responses. No differences in DPOAE response amplitudes were observed at any tested frequency in geriatric cats compared to control cats, reflecting an apparent absence of loss of cochlear outer hair cells along the length of the cochlea. No linear regression relationships were found for DPOAE response amplitude versus age in geriatric cats, despite the progressive nature of age-related hearing loss in other species. The absence of reductions in response at any of the tested frequencies in cats within the age span where cats are considered to be geriatric indicates that age-related hearing loss, if it does develop in cats, begins later in the life span of cats than in dogs or human beings.
Do ideology movements and legal intervention matter: A synthetic control analysis of the Chongqing Model

Abstract Institutions have a fundamental influence on the economic performance of a regime. Among the various aspects of institutions, ideology and the legal system are two important ones. Chongqing Municipality, a province-level region in China, experienced such a combination with a unique leader from late 2007 to early 2012. This paper investigates, via the Synthetic Control Method, the economic performance of Chongqing in the last 13 years. In particular, it discusses the impact of the red ideology movements and legal intervention undertaken by Bo Xilai. The results reveal that although his economic policies promoted the Chongqing economy, the Maoist political policies advocated by Bo partially undermined its economic growth in the short run.
Impulsivity and Problem Drinking in College: Examining the Mediating Role of Sex-Related Alcohol Expectancies and Alcohol Use at Sex.

ABSTRACTBackground: Dispositional impulsivity has been consistently implicated as a risk factor for problem drinking among college students and research suggests that this relationship may be explained in part by alcohol expectancies. A subset of alcohol expectancies, sex-related alcohol expectancies, is particularly linked to problem drinking among college students. The acquired preparedness model of risk postulates that people with dispositional impulsivity develop stronger sex-related alcohol expectancies, are subsequently more likely to drink at problematic levels in sexual situations, and thus, engage in more problem drinking. Objectives: Using this model, the current study examined whether sex-related alcohol expectancies and alcohol use at sex mediated the relationship between impulsivity and problem drinking among college students. Methods: College students (N = 101) completed self-report measures of alcohol use, sex-related alcohol expectancies, and five dimensions of impulsivity: negative urgenc...
Flow Liquefaction Instability as a Mechanism for Lower End of Liquefaction Charts

The state-of-the-practice uses the “simplified procedure” for evaluating liquefaction susceptibility of soils. Based on this procedure, liquefaction charts have been developed that correlate soil resistance to earthquake-induced stresses. These charts are based on case histories of past earthquakes and have proven to be useful while evaluating liquefaction susceptibility at a new site. However, these charts are inherently empirical, which makes extrapolation into regimes with insufficient data difficult. In addition, they do not inform an engineer about the effects of liquefaction. This work hypothesizes that the lower end of liquefaction charts corresponds to soils that are susceptible to unstable flow liquefaction. A numerical investigation is undertaken, the results of which support this hypothesis. This implies that if test data at a new site correspond to the lower end of liquefaction charts, then the site may be susceptible to flow liquefaction. This in turn could provide an engineer with some predictive power regarding the effects of liquefaction.
Surgeon Preference, Influence, and Treatment of Thumb Carpometacarpal Arthritis.

Background: The purpose of this study was to evaluate current surgical practice patterns, the factors that influence these patterns, and overall trends in the treatment of thumb carpometacarpal ost...
P148 A case of a novel HLA allele generated by gene conversion detected by a next-generation sequencing assay

Due to the expanded genomic coverage of many next-generation sequencing (NGS) assays for HLA typing, and their recent introduction into immunogenetics laboratories, there has been an increase in the identification of novel alleles. While the majority of novel alleles are simple, single nucleotide polymorphisms (SNP), others require an extensive knowledge of the NGS analysis software in order to be suitably identified. Herein, we describe a case of gene conversion, a primary way in which HLA diversity is maintained, in a novel DPB1 allele. An optimized NGSgo protocol (GenDx) was used for sequencing the DPB1 locus, with analysis by NGSengine (GenDx). Initially analyzed using default parameters, including both coding and non-coding regions of the amplicon, a typing assignment of DPB1∗02:01:19, and a novel allele, similar to DPB1∗512:01, with an SNP in exon 2 was obtained. Using a lab-developed process, the data was reanalyzed using exon 2 only, with a resulting assignment of DPB1∗40:01, without mismatches. Utilizing the full amplicon and manually aligned to DPB1∗40:01, the sample was reanalyzed, revealing that the novel allele matched DPB1∗40:01 in exons 1 and 2. However, multiple mismatches were present in the remaining sequence. This result indicated that, while the 5′ end of the novel allele likely derived from DPB1∗40:01, the 3′ end may have been derived from another allele. In order to determine which DPB1 allele may have served as the template for this gene conversion event, known DPB1 alleles were manually aligned to the sample, with the finding that the sequence for DPB1∗06:01:01 was identical to the sample sequence at exons 3–5. We concluded that the novel allele likely resulted from a gene conversion event between the DPB1∗40:01 and 06:01:01 alleles. With the increased adoption of NGS assays for HLA typing, the detection of novel alleles due to gene conversion will also likely increase. With the aid of a skilled analyst, and using the comprehensive process described here, the proper identification of such alleles may be simplified and reported appropriately to the clinician.
Leap-Frog Continuous–Discontinuous Galerkin Time Domain Method for Nanoarchitectures With the Drude Model

A continuous–discontinuous Gakerkin time domain method (CDGTD) with vector basis functions is proposed to analyze the wideband response of plasmonic structures with the Drude dispersive model. Compared to the conventional time domain approaches, such as FDTD and PSTD, the unstructured mesh can provide a better geometrical approximation of curved surfaces and fine features. An EB scheme Riemann solver is employed to calculate the flux between adjacent subdomains. The relationship between the electric field and the polarization currents is modeled by a first order auxiliary differential equation (ADE). A leap-frog scheme is proposed to update Maxwell's equations, the ADEs of the Drude medium and the perfectly matched layer (PML) in an efficient manner. This new approach is validated by virtue of simulating the ultra-wideband behavior of a gold nanoloop antenna with and without a substrate as well as the reflectivity of a dual-band infrared absorber. Its advantage in computational cost is demonstrated via comparison to a commercial software package. In this light, the CDGTD method represents a more efficient forward modeling tool, which has been successfully employed here to perform a parametric study of a dual-band infrared absorber.
A Young Adult with Cough and Wheezing Since Infancy

A 20-year-old man presented for outpatient evaluation of treatment options for recurrent respiratory papillomas. He was born with vocal cord paralysis. At 4 weeks of life, he underwent tracheostomy. In childhood his tracheostomy was closed, and he was found to have occasional, small papillomas in the trachea. During puberty, he experienced a dramatic increase in the number and size of the papillomas.
Arthroscopic Load-Shift Technique for Intraoperative Assessment of Shoulder Translation

Abstract Shoulder instability represents a spectrum of disease, ranging from subluxation to dislocation. It may present acutely after trauma or chronically as a result of multiple events. Physical examination is a key component in evaluating the degree of instability and laxity present; however, in-office guarding or apprehension may limit the examination. In addition, patient anatomy or operator technique may limit the accuracy and reproducibility of examination maneuvers such as the load-shift test. We propose an arthroscopic modification to the load-shift technique involving direct visualization to assess the direction and degree of shoulder instability. Our technique allows for the examination of a fully relaxed, anesthetized patient, eliminating guarding, and allows for intraoperative documentation of the patient's laxity both before and after surgical stabilization. In addition, this allows for custom titration of adjunctive capsulorrhaphy in arthroscopic stabilization cases.
RECURRENT TAKOTSUBO SYNDROME: FREQUENCY, PATIENT PROFILE, AND OUTCOMES

akotsubo syndrome (TTS) is a novel acute cardiac condition frequently preceded by a stressful trigger. Recurrent TTS events (RE) have been described, although the frequency, characteristics, and outcomes is largely unknown. From a single center TTS experience, we identified patients with ≥1 RE.
Systematic Review of Behavioral Weight Management Program MOVE! for Veterans.

Context Since 2006, the Veterans Health Administration has delivered a population-based behavioral weight management program (MOVE!) to Veterans, which numerous studies have examined. The purpose of this study was to systematically review these studies to understand MOVE! participation rates and the association between MOVE! participation and weight change. Evidence acquisition A December 2016 PubMed search identified 320 English-language abstracts published between January 1, 2005 and December 31, 2016, of which 42 underwent full-text review. Twenty-six articles were determined to be eligible for final inclusion and data elements extracted from these articles included study years, study design, content of MOVE! and control intervention (if any), inclusion/exclusion criteria, initial sample size and sample loss, intervention duration and follow-up, patient characteristics, and outcomes. Quality was assessed using the Newcastle–Ottawa Quality Scale. Evidence synthesis Studies were judged to be of good quality. Twenty-one of the 26 studies were retrospective cohort studies, one was a prospective cohort study and four were randomized trials. Program participation varied substantially (2%–12%) across studies. Six-month weight loss ranged from –0.95 kg to –1.84 kg, whereas 12-month weight loss ranged from –0.13 kg to –3.3 kg. A maximum of 25% of MOVE! users engaged in intense and sustained participation (eight or more visits within 6 months), but higher participation levels were consistently associated with greater weight change (–1.18 kg to –5.3 kg at 6 months, –1.68 kg to –3.58 kg at 12 months). Conclusions MOVE! participation is associated with modest short-term weight loss, with greater weight loss as participation increases. More research is needed to understand the barriers and facilitators to participation and the effect of MOVE! participation on long-term health and economic outcomes.
Neo-pragmatism, morality, and the specification problem

A defender of any view of moral language must explain how people with different moral views can be be talking to each other, rather than past each other. For expressivists this problem drastically ...
Reward-Based Learning as a Function of Severity of Substance Abuse Risk in Drug-Naïve Youth with ADHD.

Abstract Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with elevated risk for later development of substance use disorders (SUD), specifically because youth with ADHD, similar to individuals with SUD, exhibit deficits in learning abilities and reward processing. Another known risk factor for SUD is familial history of substance dependence. Youth with familial SUD history show reward processing deficits, higher prevalence of externalizing disorders, and higher impulsivity scores. Thus, the main objective of this proof-of-concept study is to investigate whether risk loading (ADHD and parental substance use) for developing SUD in drug-naive youth impacts reward-related learning. Methods: Forty-one drug-naive youth, stratified into three groups: Healthy Controls (HC, n = 13; neither ADHD nor parental SUD), Low Risk (LR, n = 13; ADHD only), and High Risk (HR, n = 15; ADHD and parental SUD), performed a novel Anticipation, Conflict, and Reward (ACR) task. In addition to conventional r...
Do optimism and pessimism predict physical functioning

Dispositional optimism has been shown to be related to self-report measures of health and well-being, yet little research has examined the relationship between optimism and more objective measures of functioning. The purpose of this study was to examine the relationship between optimism and pessimism and objective physical functioning. Four hundred eighty community-dwelling older adults with knee pain completed a measure of optimism and pessimism and were observed performing four daily activities (walking, lifting an object, climbing stairs, and getting into and out of a car). Results indicated that pessimism was significantly related to performance on all four tasks (p < .001), while optimism was related to performance only on the walking task (p < .05), after controlling for demographic and health variables.
The design of an undergraduate web application development course using free technologies and learning materials

In this paper, the authors present their experience associated with the development of a course on web-application development. The audience for the course comprises of non-traditional, adult students who are enrolled in undergraduate programs in Computer Science, Information Systems, and Informatics. The courses in these curricula are covered at an accelerated pace, in academic terms spanning 8 weeks. The paper discusses some of the constraints imposed by the short duration of the course, and describes the criteria used in the selection of topics, learning materials, class activities and evaluation methods. While the experience described here is based on an 8-week term, it can serve as a basis for the design and implementation of a course in web-application development that is offered terms of other durations as well.
Is a Lie a Lie if Everyone Knows it's a Lie?

According to a standard philosophical definition of lying, you lie if you make a statement that you do not believe with the intent to deceive (cf. Mahon 2008). Moral philosophers (e.g., Augustine 395, Kant 1797, Bok 1978, Korsgaard 2007, Carson 2010) are primarily interested specifically in lies that are intended to deceive, and in why it is wrong to tell such lies. However, a few philosophers (e.g., Sorensen 2007, Fallis 2009, Carson 2010) claim that intuitively “bald-faced lies” (i.e., lies that everyone knows are lies) are lies, despite the fact that they are not intended to deceive. In this paper, I argue that there are good philosophical reasons to classify such bald-faced lies as lies. Bald-faced lies are assertions that share an important moral commonality with lies that are intended to deceive. In particular, both sorts of lies attempt to manipulate people by violating an important social norm (viz., the norm against communicating things that one does not believe). Appealing to work in the philosophy of language on norms of conversation (most notably, Grice 1975), I propose a new definition of lying that explicitly captures this moral commonality.