cssi/SciSciGPT-SciSciNet huggingface dataset:
Consonant perception by normals in conditions of filtering.

Consonant perception was investigated for 120 normal-hearing adults who listened to 16 consonants in a phrase context and made similarity judgements of 256 diadic stimulus pairs on a 9-point equal-appearing interval scale. Stimuli were presented at subjects' most comfortable listening levels in 3 low-pass filtered and one nonfiltered conditions. Subjects' ratings were converted to 16 X 16 full symmetric similarity matrices and submitted to INDSCAL analyses. Results revealed perceptual features common to all groups, as well as group-specific features (i.e., sibilancy, stop/continuancy, and place for nonfiltered; plosive and place for 4000-Hz low-pass; stop/continuancy and place for 2000-Hz low-pass; and voicing and stop/continuancy for 500-Hz low-pass). These results were similar to those found earlier for hearing-impaired subjects having sensorineural losses compatible with these frequency cut-offs.
School Resegregation in the Mississippi of the West: Community Counternarratives on the Return to Neighborhood Schools in Las Vegas, 1968-1994.

BackgroundSchool desegregation and resegregation in the Mountain West remain understudied despite the substantial impact the region's growth and demographic change have had on racial balance and di...
Saccharomyces cerevisiae TORC1 Controls Histone Acetylation by Signaling Through the Sit4/PP6 Phosphatase to Regulate Sirtuin Deacetylase Nuclear Accumulation.

The epigenome responds to changes in the extracellular environment, yet how this information is transmitted to the epigenetic regulatory machinery is unclear. Using a Saccharomyces cerevisiae yeast model, we demonstrate that target of rapamycin complex 1 (TORC1) signaling, which is activated by nitrogen metabolism and amino acid availability, promotes site-specific acetylation of histone H3 and H4 N-terminal tails by opposing the activity of the sirtuin deacetylases Hst3 and Hst4. TORC1 does so through suppression of the Tap42-regulated Sit4 (PP6) phosphatase complex, as sit4Δ rescues histone acetylation under TORC1-repressive conditions. We further demonstrate that TORC1 inhibition, and subsequent PP6 activation, causes a selective, rapid, nuclear accumulation of Hst4, which correlates with decreased histone acetylation. This increased Hst4 nuclear localization precedes an elevation in Hst4 protein expression, which is attributed to reduced protein turnover, suggesting that nutrient signaling through TORC1 may limit Hst4 nuclear accumulation to facilitate Hst4 degradation and maintain histone acetylation. This pathway is functionally relevant to TORC1 signaling since the stress sensitivity of a nonessential TORC1 mutant (tco89Δ) to hydroxyurea and arsenic can be reversed by combining tco89Δ with either hst3Δ, hst4Δ, or sit4Δ. Surprisingly, while hst3Δ or hst4Δ rescues the sensitivity tco89Δ has to low concentrations of the TORC1 inhibitor rapamycin, sit4Δ fails to do so. These results suggest Sit4 provides an additional function necessary for TORC1-dependent cell growth and proliferation. Collectively, this study defines a novel mechanism by which TORC1 suppresses a PP6-regulated sirtuin deacetylase pathway to couple nutrient signaling to epigenetic regulation.
Chemical transport model simulations of organic aerosol in southern California: model evaluation and gasoline and diesel source contributions

Abstract. Gasoline- and diesel-fueled engines are ubiquitous sources of air pollution in urban environments. They emit both primary particulate matter and precursor gases that react to form secondary particulate matter in the atmosphere. In this work, we updated the organic aerosol module and organic emissions inventory of a three-dimensional chemical transport model, the Community Multiscale Air Quality Model (CMAQ), using recent, experimentally derived inputs and parameterizations for mobile sources. The updated model included a revised volatile organic compound (VOC) speciation for mobile sources and secondary organic aerosol (SOA) formation from unspeciated intermediate volatility organic compounds (IVOCs). The updated model was used to simulate air quality in southern California during May and June 2010, when the California Research at the Nexus of Air Quality and Climate Change (CalNex) study was conducted. Compared to the Traditional version of CMAQ, which is commonly used for regulatory applications, the updated model did not significantly alter the predicted organic aerosol (OA) mass concentrations but did substantially improve predictions of OA sources and composition (e.g., POA–SOA split), as well as ambient IVOC concentrations. The updated model, despite substantial differences in emissions and chemistry, performed similar to a recently released research version of CMAQ (Woody et al., 2016) that did not include the updated VOC and IVOC emissions and SOA data. Mobile sources were predicted to contribute 30–40 % of the OA in southern California (half of which was SOA), making mobile sources the single largest source contributor to OA in southern California. The remainder of the OA was attributed to non-mobile anthropogenic sources (e.g., cooking, biomass burning) with biogenic sources contributing to less than 5 % to the total OA. Gasoline sources were predicted to contribute about 13 times more OA than diesel sources; this difference was driven by differences in SOA production. Model predictions highlighted the need to better constrain multi-generational oxidation reactions in chemical transport models.
The Silverton Field Experience: a model geography course for achieving high-impact educational practices (HEPs)

High-Impact Educational Practices (HEPs) are a set of specific teaching and learning approaches proven effective in university education. This paper focuses on the benefits derived from utilizing t...
Mining Epistatic Interactions from High-Dimensional Data Sets

Genetic epidemiologists strive to determine the genetic profile of diseases. Two or more genes can interact to have a causal effect on disease even when little or no such effect can be observed statistically for one or even both of the genes individually. This is in contrast to Mendelian diseases like cystic fibrosis, which are associated with variation at a single genetic locus. This gene-gene interaction is called epistasis. To uncover this dark matter of genetic risk it would be pivotal to be able to discover epistatic relationships from data. The recent availability of high-dimensional data sets affords us unprecedented opportunity to make headway in accomplishing this. However, there are two central barriers to successfully identifying genetic interactions using such data sets. First, it is difficult to detect epistatic interactions statistically using parametric statistical methods such as logistic regression due to the sparseness of the data and the non-linearity of the relationships. Second, the number of candidate models in a high-dimensional data set is forbiddingly large. This paper describes recent research addressing these two barriers. To address the first barrier, the primary author and colleagues developed a specialized Bayesian network model for representing the relationship between features and disease, and a Bayesian network scoring criterion tailored to this model. This research is summarized in Section 2. To address the second barrier the primary author and colleagues developed an enhancement of Greedy Equivalent Search. This research is discussed in Section 3. Background is provided in Section 1.
Securing communication between service providers and road side units in a connected vehicle infrastructure

Road Side Units (RSUs) within the connected vehicle infrastructure are vulnerable to security and access control challenges. RSUs may share resources with unreliable SPs that could lead to information leakage due to an insecure messaging infrastructure. To mitigate these concerns, we introduce an automated service provision mechanism that enables a controlled messaging infrastructure using a Distributed Security Framework (DSF). Service provision is accomplished by providing RSUs with publish/subscribe brokers that enable authorized SPs to distribute their services as topics and define access rights through the DSF. The DSF acts as a secure middle layer that is hosted by fog computing nodes to ensure close proximity to RSUs, handles resource authorization (i.e., topic creation in specific brokers), and provides identity authentication of both RSUs and SPs. The DSF uses an attribute-based access control model to enable both SPs and RSUs to define and dynamically manage attribute-based access policies to cope with run-time changes of protection requirements. We validate the DSF framework in a simulated smart highway environment comprising interconnected RSUs and SPs to demonstrate our technique's effectiveness.
Shiraz Maher, Salafi-Jihadism: The History of an Idea, Oxford: Oxford University Press, 2016. 292 pages, $29.93, Hardcover. ISBN: 978-0190651121

This is an important study of the ideology and propagation of Salafi-Jihadism. While the term Salafi has become somewhat common in media usage, it is not well understood. Maher defines Salafism as ...
Regulation of the ATF3 gene by a single promoter in response to amino acid availability and endoplasmic reticulum stress in human primary hepatocytes and hepatoma cells.

Abstract Activating transcription factor 3 (ATF3) is a highly regulated protein that is implicated in a wide range of pathological conditions including inflammation and transformation. Transcription from the ATF3 gene is induced by several stress-induced signaling pathways , including amino acid limitation (amino acid response, AAR) and ER stress (unfolded protein response, UPR). Induction of ATF3 transcription by these pathways is mediated by ATF4 and cJUN recruitment to enhancer elements within the ATF3 gene. Although a canonical promoter (promoter A) has been studied by numerous laboratories, a second promoter activity (promoter A1), 43 kb upstream of the first, has been reported to respond to stress-induced signaling and to be critical for ATF3 expression in certain transformed cells. The results of the present study show that in normal human hepatocytes and HepG2 human hepatoma cells both basal as well as AAR- and UPR-induced transcription occurs almost exclusively from promoter A. This selectivity between the two promoters correlated with increased binding of ATF4, recruitment of RNA polymerase II , and the expected histone modifications in the promoter A region of the gene. Time course studies of ATF3 transcription activity revealed that the temporal kinetics for ATF3 induction differ between the AAR and UPR, with the former being more transient than the latter. Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals.
Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the Coronary Artery Risk Development in Young Adults Study.

Objective Determine associations of cardiorespiratory fitness, exercise systolic blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise test performed years preceding pregnancy with odds of preterm birth (PTB; Design Prospective, longitudinal. Setting Multi-site, observational cohort study initially consisting of 2787 black and white women aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011). Population 768 nulliparous women at baseline who reported ≥1 live birth by the Y25 exam. Methods We used Poisson regression to determine associations of exposures with PTB/SGA. Main outcome measures PTB and/or SGA births. Results Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer years of education and were more likely to be black versus women without PTB/SGA (n = 546). Women with PTB/SGA had lower fitness (501 ± 9 versus 535 ± 6 seconds, P Conclusions Neither fitness nor haemodynamic responses to exercise a median of 5 years preceding pregnancy, were associated with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not detectable by low fitness or exercise haemodynamic responses 5 years preceding pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more useful when conducted closer to the onset of pregnancy. Tweetable abstract Exercise testing conducted >5 years before pregnancy may not detect women likely to have PTB/SGA.
Towards Evolutionary Named Group Recommendations

When sharing information, a common tactic for reducing the cost of choosing recipients is to form named groups of users. These groups are then selected as recipients in lieu of or in addition to users. However, keeping named groups up to date is a difficult and error-prone task when conducted manually. Past schemes automating this task make different tradeoffs and can be distinguished based on several factors including the types of named groups they consider, whether they evolve a specific group or a set of multiple groups, and how integrated they are with techniques for predicting initial groups. We analyze these approaches and identify a design space of potential evolutionary approaches. Using this analysis, we introduce a novel approach for automatically suggesting a sub-type of evolution, evolutionary growth. This approach (a) requires no prior knowledge of which groups change, (b) composes, and therefore interoperates, with an existing engine for recommending named groups, and (c) extracts groups from the social graph of multiple types of applications regardless of whether the graph are explicit or derived implicitly from message communication. Our evaluation considers social graphs created using explicit and implicit connections, and identifies the conditions under which the approach outperforms baseline techniques.
Medicolegal Issues Regarding Mohs Micrographic Surgery

Almost two thirds of US physicians can expect to be sued at least once during their career. The key, however, is not to wait until that time to start learning about medicolegal issues. A physician with preemptive knowledge about the legal system can incorporate such information into a Mohs practice, thereby enhancing patient safety while minimizing malpractice risk. Physicians armed with legal information can also be better prepared to properly respond to adverse events, such as those that can occur in Mohs surgery. Not all adverse events, however, need to proceed to litigation. When an adverse event occurs, there is much a physician can do to enhance patient well-being, restore trust, and hopefully keep the issue out of court. Should the matter in fact proceed to a lawsuit, a physician with legal knowledge can be in a better position to prevent typical missteps and mount an aggressive defense.
Electron Capture by U 9 1 + and U 9 2 + and Ionization of U 9 0 + and U 9 1 +

Experimental cross sectons at energies of 962 and 437 MeV/nucleon are reported for U/sup 92 +/arrow-right-leftU/sup 91 +/ and U/sup 91 +/arrow-right-leftU/sup 90 +/ in Mylar, Cu, and Ta, as well as equilibrium charge-state distributions in these materials. At 962 MeV/nucleon a beam containing over 85% bare U/sup 92 +/ nuclei is obtained.
Wave Height Prediction in Coastal Water of Southern North Sea

Abstract The paper discusses local effects such as wave refraction due to the irregular bottom topography in the nearshore region around the East Anglian Coast. It demonstrates how wave refraction and shoaling effects could be introduced into a simple wind-wave relation in order to form a basic model to estimate wave height in the area. Results from the study suggest that locality is rather important to the predictibility of the sea surface waves in the region being investigated.
Enhanced visualization of time series through higher Fourier harmonics

Visualization techniques can enable the exploration and detection of patterns and relationships in a complex data set by presenting the data in a graphical format in which the key characteristics become more apparent. A new visualization technique, the first Fourier harmonic projection (FFHP) was introduced to translate the multi-dimensional data into a two dimensional scatter plot where the spatial relationship of the points reflects the structure of the original data set. FFHP has been shown capable of visualizing various gene expression data sets. However, dimension arrangement is crucial for the effectiveness of FFHP and certain data, such as time series, prevents dimensions (time points) from being freely rearranged. In this paper, we present an alternative approach through higher Fourier harmonic projections to enhance the visualization. Our algorithm takes advantage of the theoretical meaning of the Fourier harmonics and "reshuffles" the dimensions of the data set without physically rearranging them. The experimental results demonstrated significant improvement of the visualizations.
Environmental Health and Safety: Social Aspects

Environmental impacts on health have long been a major concern of social reformers, forward-looking health professionals, and social movements. The state of a society's environmental health is very related to its social and economic organization. The huge upsurge of synthetic chemicals since World War II has altered the environment in dramatic ways, leading to increased cancers of various types and to other diseases. Actual and potential environmental hazards and catastrophes have become a significant component of the cultural milieu of many societies. Since the 1970s, action by affected citizens has created a major social movement of toxic waste activism that has played a major role in public life, especially in the USA, and which has affected the broader environmental movement. In tandem with lay activism, novel and critical approaches by some epidemiologists and other scientists has led to many new approaches to demonstrating links between toxins and health effects.
A simplified urban-extent algorithm to characterize surface urban heat islands on a global scale and examine vegetation control on their spatiotemporal variability

Abstract We develop a new algorithm, the simplified urban-extent (SUE) algorithm, to estimate the surface urban heat island (UHI) intensity at a global scale. We implement the SUE algorithm on the Google Earth Engine platform using Moderate Resolution Imaging Spectroradiometer (MODIS) images to calculate the UHI intensity for over 9500 urban clusters using over 15 years of data, making this one of the most comprehensive characterizations of the surface UHI to date. The results from this algorithm are validated against previous multi-city studies to demonstrate the suitability of the method. The dataset created is then filtered for elevation differentials and percentage of urban area and used to estimate the diurnal, monthly, and long-term variability in the surface UHI in different climate zones. The global mean surface UHI intensity is 0.85 °C during daytime and 0.55 °C at night. Cities in arid climate show distinct diurnal and seasonal patterns, with higher surface UHI during nighttime (compared to daytime) and two peaks throughout the year. The diurnal variability in surface UHI is highest for equatorial climate zone (0.88 °C) and lowest for arid zone (0.53 °C). The seasonality is highest in the snow climate zone and lowest for equatorial climate zone. While investigating the change in the surface UHI over a decade and a half, we find a consistent increase in the daytime surface UHI in the urban clusters of the warm temperate climate zone (0.04 °C/decade) and snow climate zone (0.05 °C/decade). Only arid climate zones show a statistically significant increase in the nighttime surface UHI intensity (0.03 °C/decade). Globally, the change is mainly seen during the daytime (0.03 °C/decade). Finally, the importance of vegetation differential between urban and rural areas on the spatiotemporal variability is examined. Vegetation has a strong control on the seasonal variability of the surface UHI and may also partly control the long-term variability. The complete UHI data are available through this website ( https://yceo.yale.edu/research/global-surface-uhi-explorer ) and allows the user to query the UHI of urban clusters using a simple interface.
Cost Allocation and Information Technology

A central question in management accounting is the allocation of support department costs. Support departments provide services to operating departments that directly add value to a product or service in the firm. The increasing use of information technology (IT) has resulted in the creation of another important cost category that contributes to overhead costs. Although increases in IT spending are expected to increase productivity and profitability, the results were typically mixed. This phenomenon has historically been labeled “the productivity paradox.” Recently, IT has more rapidly increased productivity and profitability in various organizations, but the productivity increase has been erratic and inconsistent. To remain competitive, managers have had to respond to these technological changes by investing heavily in IT. Hence, justifying IT expenses has been an increasing conundrum for CIOs of most organizations. The paper provides insight into cost allocation methods that can be used to distribute IT costs. An illustrative case study provides additional insights. Three methods of varying complexity and accuracy are utilized by most organizations. From the case analysis, the reciprocal method is shown to allocate IT costs better than the direct and step-down methods. Managerial insights are provided to technology managers.
Orders and Euler’s Theorem

This chapter concludes the theory needed to describe the cryptography in Chap. 9. The key concept is that of the order of a unit b modulo m, and Euler’s Theorem, which places a constraint on the possible values of the order of b. When m is prime, Euler’s Theorem is the same as Fermat’s Theorem, which is given a proof using the Binomial Theorem. The final section describes an efficient algorithm for computing a high power of a number modulo m. This algorithm will have both an obvious use in using the cryptosystems presented in Chaps. 9 and 13 and a less obvious use to help construct cryptosystems in the last section of Chap. 9.
Global transport of dust emitted from different regions of the Sahara

Abstract An improved understanding of how emissions from different regions are transported globally is necessary to establish stronger causal relationships between particulate matter emissions and global scale circulation. This study uses the GEOS-Chem global chemical transport model to identify spatial differences in the transport of Saharan dust emitted from different regions in Northern Africa, during different seasons, and in different particle size modes. This study finds noticeable spatial differences in the transport of dust emitted from each region of the Sahara and during each season. Dust emitted from the northern regions of the Sahara undergoes 25% more latitudinal and 2% more longitudinal transport than dust emitted from the more southern regions. Dust originating from the central regions of the Sahara experiences 28% and 11% more longitudinal transport than dust from western and eastern regions, respectively. Dust emitted from the Sahara during the period from April to June travels 10%, 25%, and 17% percent further latitudinally, longitudinally, and vertically, respectively, than the annual average. As expected coarse mode particles travel shorter distances than fine mode particles. Rather than determining the regions which produce the most dust, we focus on identifying the regions producing the dust that is most extensively transported.
Determining effective bending stiffness of fabrics and other materials from tests involving an added weight

It is often desired to determine the bending stiffness of a fabric or other material. Some simple tests have been utilized for this purpose. The tests considered here involve a horizontal cantileve...
Group-Connected Multilayer Perceptron Networks

Despite the success of deep learning in domains such as image, voice, and graphs, there has been little progress in deep representation learning for domains without a known structure between features. For instance, a tabular dataset of different demographic and clinical factors where the feature interactions are not given as a prior. In this paper, we propose Group-Connected Multilayer Perceptron (GMLP) networks to enable deep representation learning in these domains. GMLP is based on the idea of learning expressive feature combinations (groups) and exploiting them to reduce the network complexity by defining local group-wise operations. During the training phase, GMLP learns a sparse feature grouping matrix using temperature annealing softmax with an added entropy loss term to encourage the sparsity. Furthermore, an architecture is suggested which resembles binary trees, where group-wise operations are followed by pooling operations to combine information; reducing the number of groups as the network grows in depth. To evaluate the proposed method, we conducted experiments on different real-world datasets covering various application areas. Additionally, we provide visualizations on MNIST and synthesized data. According to the results, GMLP is able to successfully learn and exploit expressive feature combinations and achieve state-of-the-art classification performance on different datasets.
Dependable Adaptive Mobility in Vehicular Networks for Resilient Mobile Cyber Physical Systems

Improved safety, high mobility and environmental concerns in transportation systems across the world and the corresponding developments in information and communication technologies continue to drive attention towards Intelligent Transportation Systems (ITS). This is evident in advanced driver-assistance systems such as lane departure warning, adaptive cruise control and collision avoidance. However, in connected and autonomous vehicles, the efficient functionality of these applications depends largely on the ability of a vehicle to accurately predict it operating parameters such as location and speed. The ability to predict the immediate future/next location (or speed) of a vehicle or its ability to predict neighbors help in guaranteeing integrity, availability and accountability, thus boosting safety and resiliency of the Vehicular Network for Mobile Cyber Physical Systems (VCPS). In this paper, we proposed a secure movement-prediction for connected vehicles by using Kalman filter. Specifically, Kalman filter predicts the locations and speeds of individual vehicles with reference to already observed and known information such posted legal speed limit, geographic/road location, direction etc. The aim is to achieve resilience through the predicted and exchanged information between connected moving vehicles in an adaptive manner. By being able to predict their future locations, the following vehicle is able to adjust its position more accurately to avoid collision and to ensure optimal information exchange among vehicles.
E-210 An in vitro study of intraneurysmal pressure increases during contrast injections in cerebral angiography

Introduction During angiography, the contrast bolus injected into a vessel can cause substantial changes in baseline pressures and flows.1 There have been sparse case reports about aneurysmal re-bleeds during angiography.2 A physician survey of injection rates used during angiography showed that 81% of respondents considered the impact of injection rate on aneurysm rupture to be negligible .3 The goals of this study were to record intraneurysmal pressure changes during contrast injections and to evaluate the effect of injection conditions on intraneurysmal pressure changes. Methods A silicone replica of a complete circle of Willis model with ophthalmic, anterior communicating, and basilar tip aneurysms was connected to a pulsatile flow pump (Vascular Simulations, Stony Brook, NY, figure 1). Catheters were placed in either the right internal carotid or right vertebral artery and a total of 144 injections were performed by varying 4 different parameters: Catheter Size, Injection Rate, Injection Time, mean Baseline Blood Flow rate (table). The effect of each of the four injection parameters on percentage increase in aneurysm pressures was statistically assessed using ANCOVA; baseline pressure was considered a covariate. Results The mean intraneurysmal pressure during injection (84.5±10.8 mmHg) was significantly higher than the mean pressure before injection (80.4±10.6 mmHg) (p 0.2) and Baseline Blood Flow rate (p>0.3) had no significant effect on the increase in intraneurysmal pressure. Conclusion Our results suggest that higher contrast Injection Rates can significantly increase intraneurysmal pressures during angiography. Whether a ~5% increase in intraneurysmal pressure can cause aneurysm rupture needs to be evaluated. Angiography studies need to be conducted in vivo to verify these findings. References Kovarovic B, et al. Cardiovasc Eng Technol 2018;9(2):226–239. Celtikci P, et al. Turk Neurosurg 2018;28(6):1009–1012. Yousem, DM, et al. AJNR 2001;22:1838–1840. Disclosures S. Marfoglio: 5; C; Vascular Simulations, Inc. B. Kovarovic: None. W. Hou: None. D. Fiorella: 4; C; Vascular Simulations Inc. C. Sadasivan: 2; C; Vascular Simulations Inc. 4; C; Vascular Simulations Inc. 6; C; Vascular Simulations Inc.
Abstract B08: Identification and characterization of Rho family GTPases as drivers of drug resistance in BRAFV600 mutant melanoma

The serine/threonine protein kinase BRAF is mutated in approximately 50% of cutaneous melanomas, leading to hyperactivation of the MAPK/ERK pathway. The most common mutations, BRAFV600, can be targeted by selective kinase inhibitors, such as vemurafenib. Although initial clinical response to BRAF inhibition (BRAFi) is encouraging, 90% of patients develop drug resistance within a few months. Drug resistance can be delayed, but not prevented, by combining BRAFi with an MEK inhibitor (MEKi), such as cobimetinib. While some resistance mechanisms are known, disease progression on drug cannot be explained in all patients. We performed a gain-of-function mutagenesis screen utilizing the Sleeping Beauty transposon system to identify novel drivers of resistance in BRAFV600E mutant melanoma cells sensitive to current therapies. We chose four of the top candidates from our screen and validated the ability to drive resistance to both vemurafenib and vemurafenib-cobimetinib combination treatment in multiple melanoma cell lines. In an effort to determine the broader role of candidate vemurafenib-resistance drivers, we conducted an additional in vivo mutagenesis screen, of which genetic analysis is ongoing. Our initial cell-based screen identified two members of the Dbl family of guanine nucleotide exchange factors (GEFs), VAV1 and MCF2, as candidate drivers of vemurafenib resistance. A375 melanoma cells overexpressing VAV1 or MCF2 maintain significant growth under vemurafenib treatment, while control cells do not. Functional tests of VAV1 and MCF2 identified that the active form of two Rho family members, RAC1 and CDC42, increases following treatment with vemurafenib, suggesting a PAK-mediated pathway of resistance. In addition, all candidates that were tested elevated ERK signaling in the presence of vemurafenib. Many of the extracellular signaling pathways known to drive increased vemurafenib resistance activate Rho signaling. Our results suggest that Dbl family members may play an important role in this process. Understanding how Rho activation occurs and its consequences for drug resistance in melanoma will provide critical insights into the design and validation of future targeted therapies. Citation Format: Jacob L. Schillo, Charlotte R. Feddersen, Afshin Varzavand, Hayley R. Vaughn, Lexy S. Wadsworth, Andrew P. Voigt, Eliot Y. Zhu, Jesse D. Riordan, Christopher S. Stipp, Adam J. Dupuy. Identification and characterization of Rho family GTPases as drivers of drug resistance in BRAFV600 mutant melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B08.
Psychosocial Evaluation Matters.

Transplant clinicians who focus on psychosocial issues know how critical the pre-transplant psychosocial evaluation is for facilitating patients' successful negotiation of the transplantation process. This is particularly the case in liver transplantation: psychosocial factors such as substance use and dependence have often directly contributed to the need for transplantation, and substance use history is often entwined with other psychosocial liabilities such as poor mental health and weak social support. Indeed, the overall value of the psychosocial evaluation as part of the medical work-up for liver and other types of solid organ transplantation is well-recognized in clinical practice guidelines and recommendations.(1-3).
When Being Connected is Not Enough. An Analysis of the Second and Third Levels of the Digital Divide in a Developing Country

The Internet has been identified as a tool to overcome poverty; by improving communication, facilitating innovation, and driving economic growth. However, as seen in studies on the benefits of Internet adoption and use, the welfare effect of technology is not only based on its adoption, but also on the type of use. In this study, drawing on the Uses and Gratifications Theory, we identified distinct classifications and predictors of Internet activities (second-level digital divide) and Internet outcomes (third-level digital divide) relevant to Sub-Saharan Africa. Gender, age, and educational level are key predictors of the second-level digital divide, while educational level and Internet use patterns affect the third-level digital divide.
Using Novel Statistical Techniques to Accurately Determine the Predictive Dose Range in a Study of Overall Survival after Definitive Radiotherapy for Stage III Non-Small Cell Lung Cancer in Association with Heart Dose.

Purpose: Recent studies of radiotherapy (RT) for stage III non-small-cell lung cancer (NSCLC) have associated high dose to the heart with cardiac toxicity and decreased overall survival (OS). We used advanced statistical techniques to account for correlations between dosimetric variables and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC. Methods: From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS data was obtained from institutional tumor registry. We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates. We subsequently used novel statistical techniques within multivariate Cox model to systematically search the whole heart dose-volume histogram (DVH) for dose parameters associated with OS. Results: Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH, the dose of 51 Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified V55Gy (percentage of the whole heart volume receiving at least 55 Gy) as the best single DVH index which can be used to set treatment optimization constraints (Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55 Gy, P = 0.03). Additional characteristics correlated with OS on multivariate analysis were age, stage (IIIA/IIIB), and administration of chemotherapy. Conclusion: Doses above 51 Gy, applied to small volumes of the heart, are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS.
Assessing Relational Learning Deficits in Perspective-Taking in Children with High-Functioning Autism Spectrum Disorder

Perspective-taking, or the ability to demonstrate awareness of informational states in oneself and in others, has been of recent interest in behavioral psychology. This is, in part, a result of a modern behavioral approach to human language and cognition known as Relational Frame Theory, which views perspectivetaking as generalized operant behavior based upon a history of reinforcement for relational responding. Previous lines of research have developed a behavioral protocol for assessing relational learning deficits in perspective-taking and have implicated the lack of perspective-taking as a basis for the social deficits observed in children with autism. However, no empirical investigations have been conducted on relational learning deficits in perspective-taking with autistic populations. The present paper reports 2 experiments that investigated whether children with autism spectrum disorder demonstrated relational learning deficits in a perspective-taking task as compared to their age-matched typicalill developing peers. We also investigated whether accuracy in perspective-taking correlated with scores on standardized instruments commonly used in the assessment of autism spectrum disorder, and whether relational responding in perspective-taking improves following a history of reinforcement for such responding. Results of Experiment 1 demonstrated statistically significant differences in errors as a function of type of relation, while visual inspection revealed that partiCipants with autism spectrum disorder made more errors than typically developing children on 2 of the 3 types of relations examined. Results of Experiment 2 illustrated that a history of reinforced relational responding improved performance on the perspective-taking task.
Analog amplitude modulation of a high voltage, solid state inductive adder, pulse generator using MOSFETs

High voltage, solid state, inductive adder, pulse generators have found increasing application as fast kicker pulse modulators for charged particle beams. The solid state, inductive adder, pulse generator is similar in operation to the linear induction accelerator. The main difference is that the solid state, adder couples energy by transformer action from multiple primaries to a voltage summing stalk, instead of an electron beam. Ideally, the inductive adder produces a rectangular voltage pulse at the load. In reality, there is usually some voltage variation at the load due to droop on primary circuit storage capacitors, or, temporal variations in the load impedance. Power MOSFET circuits have been developed to provide analog modulation of the output voltage amplitude of a solid state, inductive adder, pulse generator. The modulation is achieved by including MOSFET based, variable subtraction circuits in the multiple primary stack. The subtraction circuits can be used to compensate for voltage droop, or, to tailor the output pulse amplitude to provide a desired effect in the load. Power MOSFET subtraction circuits have been developed to modulate short, temporal (60-400 ns), voltage and current pulses. MOSFET devices have been tested up to 20 Amps and 800 Volts with a band pass of 50 MHz. An analog modulation cell has been tested in a five cell high, voltage adder stack.
ENZYMES OF THE PYRIMIDINE PATHWAY IN ESCHERICHIA COLI I. Synthesis by Cells and Spheroplasts

Taylor, W. Herman (Portland State College, Portland, Ore.), and G. David Novelli. Enzymes of the pyrimidine pathway in Escherichia coli. I. Synthesis by cells and spheroplasts. J. Bacteriol. 88:99–104. 1964.—Upon release from repression, cells and spheroplasts of two mutants of Escherichia coli efficiently synthesized aspartate transcarbamylase and ornithine transcarbamylase, whereas only cells synthesized dihydroorotic dehydrogenase. Ethylenediaminetetraacetate treatment and sucrose incubation of cells were found to be responsible for the loss of dihydroorotic dehydrogenase synthesis. Spheroplasts required the addition of amino acids and an energy source for the synthesis of aspartate transcarbamylase. Uracil repressed synthesis of aspartate transcarbamylase in spheroplasts as well as in cells. Chloramphenicol inhibition and amino acid requirement for increased aspartate transcarbamylase activity in spheroplasts indicated de novo protein synthesis. E. coli 15, R185-482, and E. coli K-12, 496, were used to study the effect of carbon source and stimulation by orotate and dihydroorotate on synthesis of dihydroorotic dehydrogenase. Only E. coli 15, R185-482, showed any stimulation of dihydroorotic dehydrogenase synthesis. When glucose was the carbon source, orotate but not dihydroorotate stimulated; with glycerol as carbon source, dihydroorotate stimulated and orotate acted as a repressor. These results are discussed in terms of induction and pyrimidine supply to the cells.
Electron impact excitation of the singlet and triplet B1u π → π∗ states of ethylene near threshold

Abstract The electron impact excitation functions of the 1 3 B 1 u and 1 1 B 1 u π → π ∗ states of ethylene are measured. The triplet excitation function has a broad peak near 6.5 eV that is attributed to the π −1 (π ∗ ) 2 anion state, and the singlet excitation function displays sharp structure near threshold due to the π−1(3s)2 anion state.
Requirements for Growth of Single Human Cells: "Nonessential" amino acids, notably serine, are necessary and sufficient nutritional supplements

A minimal growth medium supplemented with dialyzed serum, which sufficed for the propagation of a wide variety of human cell strains in heavily inoculated monolayer and suspension cultures, did not permit the regular or optimal growth of small numbers of HeLa, HeLa S3, conjunctiva, or KB cells deriving from suspension cultures. At threshold concentrations of serum, the plating efficiency of single cells was greatly reduced as compared with their plating efficiency in a medium containing dialyzed serum instead of whole serum, and the clones which did develop grew at a slower rate. The nutritional deficiency could be overcome by adding the seven amino acids which are ordinarily not nutritionally essential. In most of the experiments serine alone sufficed.
Phylogenetic perspective on ecological niche evolution in american blackbirds (Family Icteridae)

Analysis of ecological characters on phylogenetic frameworks has only recently appeared in the literature, with several studies addressing patterns of niche evolution, generally over relatively recent time frames. In the present study, we examined patterns of niche evolution for a broad radiation of American blackbird species (Family Icteridae), exploring more deeply into phylogenetic history. Within each of three major blackbird lineages, overlap of ecological niches in principal components analysis transformed environmental space varied from high to none. Comparative phylogenetic analyses of ecological niche characteristics showed a general pattern of niche conservatism over evolutionary time, with differing degrees of innovation among lineages. Although blackbird niches were evolutionarily plastic over differing periods of time, they diverged within a limited set of ecological possibilities, resulting in examples of niche convergence among extant blackbird species. Hence, an understanding of the patterns of ecological niche evolution on broad phylogenetic scales sets the stage for framing questions of evolutionary causation, historical biogeography, and ancestral ecological characteristics more appropriately. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 94, 869–878.
Social Science Concepts of Modernization and Biblical History: The Development of the Israelite Monarchy

EW periods of biblical history have attracted as much study and concern as that of the development of the monarchy. The text has been carefully scrutinized and analyzed from most every conceivable point of view. Comparisons, all tentative because of the paucity of sources, with neighboring peoples have been suggested. While a fairly clear reconstruction is now possible, modern social science has provided further comparisons which can also aid in our understanding. Seldom have concepts developed by those concerned with modernization in the social sciences been utilized in the study of ancient history. The span of time and the concern for what are apparently vastly different cultural settings have caused the reticence. The emergence of over one hundred new nations since the French Revolution has led to detailed studies of the processes of their development and the formulating of conceptual tools to enable a clearer understanding of them. While acknowledging important and numerous differences, there does seem to be considerable advantage in applying many of these conceptions to that period of Israelite history during which the Davidic dynasty was established.' The general conception of modernization does seem to have transchronological significance and applicability. C. E. Black defines modernization as "the process by which historically evolved institutions are adapted to the rapidly changing functions that reflect the unprecedented increase in man's knowledge permitting control over his environment."2 Furthermore, it "must be thought of then as the process that is simultaneously creative and destructive, providing new opportunities and prospects at a high price in human dislocation and suffering."3 Finally, "the models adopted by modernizing leaders except in the societies that were the 1 Martin A. Cohen, "The Role of the Shilonite Priesthood in the United Monarchy of
The clinical utility of randomized controlled trials.

Objective Efficacy studies using randomized controlled trials (RCTs), on which empirically supported treatments are based, are often rejected as having little if any relevance to clinical practice. RCTs are faulted for allegedly excluding poor prognosis patients and therapists and treatments that are unrepresentative of clinical practice. Methods: Evidence on the generalizability of findings from RCTs to diverse patient populations, different therapists, and varied clinical settings is critically evaluated. Results: Existing research indicates that RCTs commonly include patients with multiple problems and levels of disturbance as severe as patients in clinical settings. Discussion: The applicability of the findings of RCTs to clinical practice will be a changing function of the nature of the particular study and clinical setting to which the results are to be generalized. Future research should address the clinical utility of the findings of efficacy studies across different patient populations, therapists, and treatment methods. © 1998 John Wiley & Sons, Inc. Int J Eat Disord 24:13–29, 1998.
Automatic transformation of series expressions into loops

The benefits of programming in a functional style are well known. In particular, algorithms that are expressed as compositions of functions operating on sequences/vectors/streams of data elements are easier to understand and modify than equivalent algorithms expressed as loops. Unfortunately, this kind of expression is not used anywhere near as often as it could be, for at least three reasons: (1) most programmers are less familiar with this kind of expression than with loops; (2) most programming languages provide poor support for this kind of expression; and (3) when support is provided, it is seldom effcient.In any programming language, the second and third problems can be largely solved by introducing a data type called series, a comprehensive set of procedures operating on series, and a preprocessor (or compiler extension) that automatically converts most series expressions into efficient loops. A set of restrictions specifies which series expressions can be optimized. If programmers stay within the limits imposed, they are guaranteed of high efficiency at all times.A common Lisp macro package supporting series has been in use for some time. A prototype demonnstrates that series can be straightforwardly supported in Pascal.
Biographical Sketch: John Royal Moore, MD 1899–1988

This biographical sketch on John R. Moore corresponds to the historic text, The Classic: Cartilaginous-cup Arthroplasty in Ununited Fractures of the Neck of the Femur (1948), available at DOI 10.1007/s11999-011-1974-z.