cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B63: Disparities in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009

Objective: Surveillance of lung cancer by histology type is important for monitoring population trends that have implication for etiology and prevention, clinical diagnosis, prognosis and choice of targeted therapies. This study provides a comprehensive and recent description of disparities in histologic lung cancer incidence rates and trends for U.S. adults. Methods: Histologic lung cancer incidence was analyzed from CDC9s National Program of Cancer Registries (NPCR) and the National Cancer Institute9s Surveillance, Epidemiology and End Results (SEER) Program. Standardized rates and trends were calculated for men and women by age, race/ethnicity, and U.S. Census region. Rate ratios were examined for differences in rates between men and women, and annual percent change was calculated to quantify changes in incidence rates over time. Results: Adenocarcinoma and squamous cell carcinoma were the two most common histologic subtypes. Adenocarcinoma rates continued to increase in men and women, and squamous cell rates increased in women only. All histologic subtype rates for white women exceeded rates for black women, and histologic rates for black men exceeded those for white men, except for small cell carcinoma where rates were higher among white men. Among both men and women, the rate for Hispanics was nearly half the rate for non-Hispanic (NH) blacks and NH whites. Men had higher incidence rates than women for race and ethnic groups, but the relative size of this difference by sex was higher for NH blacks, NH Asian/Pacific Islanders and Hispanics compared with NH whites. The relative difference in incidence rates between men and women was slightly lower for NH American Indian/Alaska Native (AI/AN) populations than for whites. Differences between men and women living in the West were less pronounced compared to those living in other Census regions. Conclusion: The variations observed by race and ethnicity, continuing rise in incidence rates of lung adenocarcinoma, and rise of squamous cell cancer rates in women suggest more research is needed to comprehensively understand factors that may be contributing to observed differences in lung cancer histology. Identification of these factors acting in addition to, or in synergy with cigarette smoking, may provide public health agencies with guidance for targeted messages to groups at higher risk. Citation Format: Keisha Houston, S. Jane Henley, Jun Li, Mary C. White, Thomas B. Richards. Disparities in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B63.
Changes of Sleep Architecture in School-Age Children with Idiopathic Partial Epilepsy

Objective To investigate the changes of sleep architecture in school-age children with idiopathic partial epilepsy.Methods Twenty-three children with partial epilepsy(aged 6-12 years old;15 boys,8 girls)and 15 healthy children(11 boys,4 girls)who had same age and gender to the patients with partial epilepsy(healthy control group)were investigated with a national polysomnography system.The 23 children with partial epilepsy were divided into frontal lobe epilepsy group,temporal lobe epilepsy group and occipital lobe epilepsy group according to the location of epileptic discharge;according to the attack time of seizure,they were divided into sleeping seizure group,waking seizure group and full-attack group;according to the condition of antiepileptic drugs consuming,they were divided into carbamazepine(CBZ)group and CBZ+topiramate(TPM)group.They were monitored for a whole night.Most of sleep parameters were analyzed by SPSS 13.0 software between every groups.Results Compared with the healthy control group,the percentage of stage 1 in non-rapid eye movement(NREM)sleep prolonged(P0.05),while the percentage of slow wave sleep(SWS)decreased in partial epilepsy group(P0.01).For the patients with frontal lobe epilepsy,there was no significant difference compared with healthy control group,while the patients with temporal lobe epilepsy had more awaking time compared with healthy control group(P0.05).And the patients with epilepsy in sleep could awake more times than that of healthy control group(P0.05),and the percentage of stage 1 in NREM sleep also prolonged(P0.05),while the patients with waking seizure had less time in SWS compared with healthy control group(P0.05).The partial epileptics treated with CBZ+TPM had more time of rapid eye movement(REM)sleep than that of the untreated patients(P0.05).Conclusions Children with partial epilepsy had a broken sleep architecture,including more light sleep and lower deep sleep.Moreover,different kinds of partial epilepsy had different effects on sleep architecture.As to the epilepsy in wakefulness,it had slight effect on sleep architecture,but the epilepsy in sleep broke the sleep architecture.Co-treatment of CBZ and TPM improved the sleep quality in childhood partial epilepsy,and especially increased the time of REM sleep.
Which outcomes matter in Alzheimer disease and who should define them

The identification of salient outcomes depends on the conceptual map of the disease and its consequences. Early attention focuses on cognition. Cognitive losses can lead to behavioral problems, which may be exacerbated by treatment. Behavioral problems can create a need for supervision. Client functioning can require another form of supervision, cuing. Because Alzheimer disease affects families as much as patients, many outcomes are directed at measures of caregiver burden and stress. A therapeutic model of chronic care management, which aims at producing results at least as good as might be reasonably expected (i.e., slowing decline), creates a different mind set from a compensatory model of care, which seeks primarily to meet dependency needs. In the latter, good care is equivalent to meeting needs without incurring adverse events. Outcomes and locus of decision-making intersect around issues of quality of life. Assumptions about the ability of a patient with Alzheimer disease to express positive feelings or to indicate preferences for care need to be explored carefully. Although the use of agents or proxies may be necessary when making decisions about care, proxies serve poorly to convey information about another person's quality of life.
Stimulus-Dependent Oxidative Cross-Linking of a Proline-Rich Plant Cell Wall Protein: A Novel, Rapid Defense Response and Control Point in Cellular Maturation

Treatment of bean or soybean cells with fungal elicitor or glutathione causes a rapid insolubilization of pre-existing (hydroxy)proline-rich structural proteins in the cell wall. This insolubilization, which involves H2O2-mediated oxidative cross-linking, is initiated within 2 minutes and complete within 10 minutes under optimal conditions, and hence precedes the expression of transcription-dependent defense responses such as the synthesis of phytoalexin antibiotics and hydrolytic enzymes. We have obtained data that demonstrate that elicitor causes a rapid hardening of the cell wall that can be ascribed to the oxidative cross-linking of these structural proteins. Moreover, this cross-linking was observed in the early stages of an incompatible interaction, but not in a compatible interaction, between soybean and Pseudomonas syringae pv. glycinea. Cross-linking is also under developmental control associated with cellular maturation during hypocotyl growth and in tissues subject to mechanical stress such as the stem : petiole junction. Stimulus-dependent oxidative cross-linking of plant cell wall structural proteins is a novel site of cellular regulation with potentially important functions in the flexible realization of the final functional architecture of cell walls during development and rapid toughening of cell walls in the initial stages of plant defense.
Biomimicry as a basis for drug discovery.

Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term “natural product” is often used synonymously with “secondary metabolite.” Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed “inventive evolution.” It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products (“unnatural natural products”), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.
Solution-Based Techniques for Biomimetics and Bioreplication

Nature generates structurally complex architectures with feature sizes covering several length scales under rather simple environmental conditions and with limited resources. Today, researchers understand how many of these structures look and behave, but, in many instances, we still lack nature’s ability to marry elegant structures with complex functionality. By unraveling the wonders of nature’s design, scientists have developed biomimetic and biotemplated materials with entirely new functions and behaviors. In particular, solution-based methods provide simple, inexpensive routes to generating bioreplicated structures. In this chapter, we survey solution-based bioreplication methods and provide an example for generating three-dimensional photonic crystal structures based on colored weevil scales. This example illustrates how structural engineering in biology can be replicated using sol–gel chemistry and results in an entirely new optical material with fascinating properties.
Dulzor, género e identidad en el arte culinario de Japón

This paper examines confectionary as a pervasive, though relatively little discussed, aspect of contemporary and historical Japanese culinary culture. Sweets in their contemporary form trace their origins to courtly cuisine that entered Japanese food culture via contact with Portuguese traders in the 16th century. Certain types of sweets were present prior to this period, which appear to be at least in part influenced by contact with Chinese culture, though these were quite different from those that followed Portuguese contact. Sweets developed in this time period are viewed as intrinsically Japanese (wagashi) while ones that entered after the Meiji Reformation of the mid-19th century, and with greater intensity since World War II, are marked as European sweets (yogashi). Archetypal wagashi are intricately handcrafted sweets made exclusively of local Japanese ingredients, shaped in visually beautiful forms that vary in form in order to be in tune with the changing seasons, and used most importantly in the tea ceremony. Western confectionary includes European cakes, pastries, and chocolate. These different types of sweets may be placed in a range of different categories, varying according to contrasting distinctions such as Japanese versus foreign and expensive/high class sweets versus cheaper, more everyday varieties. These distinctions are not completely exclusive, however, and other factors can also play a role in defining the uses and meanings of particular types of sweets. The many uses of sweets are to a great extent governed by the varying meanings of different sweets that are largely shared by the Japanese but also differ on account of factors such as age, gender, wealth, and self-positioning in regard to a traditionalist or modernist stance. Sweets, both “Japanese” and “European”, have become important for daily consumption and for ritualized occasions. Sweets are, moreover, the quintessential gift in a culture in which gift-giving is a fundamental component of social relations, particularly the pervasive practice of giving omiyage—gifts representing a place to which one has travelled. In this practice, sweets feature as the most common and important gift. Sweets are used to mark local identities and are also highly gendered, with confectionary traditionally being the purview of women and children, although this has been reworked in intriguing ways in contemporary Japan. The most vivid example of gift-giving that is also gendered is provided by the practice carried out on the adopted holiday of Valentine’s Day. On this day, chocolate is given exclusively by women to men, sometimes as a social requirement (giri choco, obligation chocolate) to male co-workers and acquaintances as well as to one’s actual romantic interest (honmei choco, “true chocolate”). Through an exploration of a variety of sweets and their wide-ranging uses and meanings in local identities, gift exchange and gender relations, the paper aims not only to throw light on this key aspect of Japanese culinary culture, but also to use sweets as a window into broader aspects of Japanese life.
Evolution, Mobility, and Ethnic Group Formation

By drawing on ideas developed in evolutionary psychology, this article attempts to contribute to improved understanding of ethnic group formation and change. Specifically, the article asks whether and to what degree evolved mental capacities and dispositions, in interaction with human social environments, account for ethnic group formation. The central arguments are that, in recent millennia, evolved reasoning capabilities of humans have led to a revolution in the technologies of human mobility—and that this development has severed the nearly perfect association between social group formation based on functional advantages and social group formation based on perceived kinship. The scale, composition, and durability of contemporary ethnic groups are the consequence of individual tradeoffs in functionality and kinship values.
Mean field homogenization methods for strand composites

Abstract A common method for dealing with in-process manufacturing waste is to cut the prepreg scrap into rectangular strands, and use these strands to produce composites. The properties of the strand composite depend on a number of factors, including the aspect ratio and orientation of the strand. Predictive simulations are required to determine the stiffness of such materials so that optimal composites can be fabricated without extensive experimental testing. In this work, we present a hybrid method for predicting the stiffness of strand composites by using a combination of finite element and analytic mean field homogenization techniques. The proposed model combines the versatility of finite element models and the ease of computation of analytic schemes. This method can be used to model strands of any shape and orientation distribution; it also presents possibilities for detailed parametric analysis. The proposed method yields predictions that are consistent with experimental measurements and provides insights about testing protocols and observed scatter in experimental results.
First Report and Complete Genome Sequence of Alfalfa Enamovirus from Sudan.

ABSTRACT We report the complete genome sequence of a viral pathogen detected in alfalfa samples from Sudan and provisionally named alfalfa enamovirus 2 (AEV-2). Based on high nucleotide and amino acid identities, AEV-2 represents a strain of a newly discovered alfalfa enamovirus 1 that has only been described in Argentina.
Relative clauses as a benchmark for Minimalist parsing

Minimalist grammars have been used recently in a series of papers to explain well-known contrasts in human sentence processing in terms of subtle structural differences. These proposals combine a top-down parser with complexity metrics that relate parsing difficulty to memory usage. So far, though, there has been no large-scale exploration of the space of viable metrics. Building on this earlier work, we compare the ability of 1600 metrics to derive several processing effects observed with relative clauses, many of which have been proven difficult to unify. We show that among those 1600 candidates, a few metrics (and only a few) can provide a unified account of all these contrasts. This is a welcome result for two reasons: First, it provides a novel account of extensively studied psycholinguistic data. Second, it significantly limits the number of viable metrics that may be applied to other phenomena, thus reducing theoretical indeterminacy.
Miguel Székely (coord.), Números que mueven al mundo: La medición de la pobreza en México, México, ANUIES-CIDE-Sedesol, Miguel Ángel Porrúa, 2006, 912 pp.

Este libro hace varias contribuciones importantes a la bibliografia de la medicion de la pobreza y la politica publica. Primero, es una relacion de un capitulo fundamental de la historia politica y economica de Mexico --el proceso de adopcion e implantacion de la metodologia oficial de la pobreza en Mexico--, que aporta pruebas documentales de un enfoque progresista y practico para la elaboracion de politicas. Segundo, es una rica fuente de informacion respecto a los problemas conceptuales de la medicion de la pobreza y los obstaculos practicos para la aplicacion de una metodologia en el Mexico del siglo XXI. Tercero, proporciona un marco o una guia para otros paises que deseen seguir la via de Mexico hacia una transparencia mayor en la elaboracion de politicas y una mayor responsabilidad gubernamental. Por ultimo, el volumen mismo es una manifestacion de este espiritu de transparencia, y su existencia misma hace una contribucion importante hacia esta meta.
An evaluation of auditory feedback for students of dance: Effects of giving and receiving feedback

The purpose of this study was to evaluate auditory feedback for dance students on a competition team in which one peer provided auditory feedback to another peer for a selected dance movement. Some peers switched roles during the study, and increases in their performances were evaluated both as the receiver and deliverer of auditory feedback. All participants demonstrated increases in their respective target behaviors when they received auditory feedback. Several participants also displayed increases in their movements when they provided auditory feedback to their peer partner, although these increases were not as substantial as those who received feedback.
A Standard for the Scholarly Citation of Archaeological Data as an Incentive to Data Sharing

How do archaeologists share their research data, if at all? We review what data are, according to current influential definitions, and previous work on the benefits, costs, and norms of data sharing in the sciences broadly. To understand data sharing in archaeology, we present the results of three pilot studies: requests for data by e-mail, review of data availability in published articles, and analysis of archaeological datasets deposited in repositories. We find that archaeologists are often willing to share but that discipline-wide sharing is patchy and ad hoc. Legislation and mandates are effective at increasing data sharing, but editorial policies at journals lack adequate enforcement. Although most of the data available at repositories are licensed to enable flexible reuse, only a small proportion of the data are stored in structured formats for easy reuse. We present some suggestions for improving the state of date sharing in archaeology; among these is a standard for citing datasets to ensure that researchers making their data publicly available receive appropriate credit.
Prenatal and Infant Development: Overview

Since 1980 the pace of new scientific knowledge about prenatal and infant development has sharply increased, yielding a picture of an organism actively engaged in extracting information from and interacting with the world. Even the fetus is responsive to stimulation in all sensory modalities and has the capability of learning—a capacity that expands in new and increasingly sophisticated ways after birth. The effects of early experiences are both cumulative and enduring throughout the infancy period. Studies with prenates have revealed that neurally-mediated behavior following birth is continuous with behavior during the prenatal period, finally shifting from principally subcortical to increasingly cortical control between 2 and 4 months of age. This shift ushers in a rapid increase in social and other learned behaviors that, in relatively short order, will position the infant on the threshold of childhood, armed with the motoric, social, and cognitive tools necessary to cross over. This article considers the mileposts of the organism's prenatal and postnatal achievements, some of the issues that researchers have solved and others they have not, and the future prospects for infancy research.
Reduction of PDEs to a First Order System

This chapter describes the reduction of partial differential equations (PDEs) to a first-order system. By introducing variables to represent the derivatives in a partial differential equation, a first-order system may be obtained. Sometimes it is advantageous to reduce a partial differential equation of high order for a single unknown function to a system of several first-order equations. This might be done, for instance, to utilize a specific numerical package that requires a partial differential equation to be input as a first-order system. This can always be done by introducing an appropriate set of derivatives as unknowns. The general procedure is to introduce new variables as the derivatives of the desired function, and then discover relations among these functions. Systems of high order partial differential equations can also be made into first-order systems, by the introduction of enough terms.
Integrating Handheld Technology with Field Investigations in Introductory-level Geoscience Courses

Many geoscience students do not receive the opportunity to use handheld computers and similar tools during field experiences until they enroll in upper-division courses or attend field camp. Although many outdoor exercises in introductory-level courses include demonstrations of pieces of equipment in the field, students in these classes may not have a chance to use these equipment individually. However, handheld technology can be successfully integrated with introductory-level field experiences as a data collection tool and reference guide. Palm Pilot handheld computers offer each student the opportunity to become actively involved in the field experience. Forms can be created and tailored to a specific outdoor investigation and placed on the Palms for students to collect data. Instructors can create instructional videos and eBooks with references on the Palms that correspond to the project objective. For two years Penn State Delaware County has integrated handheld technology with field experiences into i...
The relationship between implicit intergroup attitudes and beliefs

Intergroup attitudes (evaluations) are generalized valence attributions to social groups (e.g., white-bad/Asian-good), whereas intergroup beliefs (stereotypes) are specific trait attributions to social groups (e.g., white-dumb/Asian-smart). When explicit (self-report) measures are used, attitudes toward and beliefs about the same social group are often related to each other but can also be dissociated. The present work used three approaches (correlational, experimental, and archival) to conduct a systematic investigation of the relationship between implicit (indirectly revealed) intergroup attitudes and beliefs. In study 1 (n = 1,942), we found significant correlations and, in some cases, evidence for redundancy, between Implicit Association Tests (IATs) measuring attitudes toward and beliefs about the same social groups (mean r = 0.31, 95% confidence interval: [0.24; 0.39]). In study 2 (n = 383), manipulating attitudes via evaluative conditioning produced parallel changes in belief IATs, demonstrating that implicit attitudes can causally drive implicit beliefs when information about the specific semantic trait is absent. In study 3, we used word embeddings derived from a large corpus of online text to show that the relative distance of 22 social groups from positive vs. negative words (reflecting generalized attitudes) was highly correlated with their distance from warm vs. cold, and even competent vs. incompetent, words (reflecting specific beliefs). Overall, these studies provide convergent evidence for tight connections between implicit attitudes and beliefs, suggesting that the dissociations observed using explicit measures may arise uniquely from deliberate judgment processes.
Frontier Intermediaries: Army Laundresses at Fort Davis, Texas

As contested spaces, frontiers are the ideal location in which to study identity, as inhabitants of these landscapes constantly experience and actively negotiate among the multiple lived realities that are shaped by conflicting ideologies. I propose the use of third-space and borderlands theory as frameworks for understanding the fluidity of experiences in the American frontier during the 19th century. Through a look at a community of laundresses in Fort Davis, Texas, I show how life on the edge—or perhaps in the middle—of geographic and social frontiers allowed inhabitants of these contested spaces to construct and redefine new personhoods. Moreover, I assert that women’s participation in food provisioning and preparation allowed them to act as cultural brokers across various scales of community interaction.
Signaling alterations caused by drugs and autophagy

Autophagy is an evolutionary conserved process that recycles cellular materials in times of nutrient restriction to maintain viability. In cancer therapeutics, the role of autophagy in response to multi-kinase inhibitors, alone or when combined with histone deacetylase (HDAC) inhibitors acts, generally, to facilitate the killing of tumor cells. Furthermore, the formation of autophagosomes and subsequent degradation of their contents can reduce the expression of HDAC proteins themselves as well as of other signaling regulatory molecules such as protein chaperones and mutated RAS proteins. Reduced levels of HDAC6 causes the acetylation and inactivation of heat shock protein 90, and, together with reduced expression of the chaperones HSP70 and GRP78, generates a strong endoplasmic reticulum (ER) stress response. Prolonged intense ER stress signaling causes tumor cell death. Reduced expression of HDACs 1, 2 and 3 causes the levels of programed death ligand 1 (PD-L1) to decline and the expression of Class I MHCA to increase which correlates with elevated immunogenicity of the tumor cells in vivo. This review will specifically focus on the downstream implications that result from autophagic-degradation of HDACs, RAS and protein chaperones.
The incredible shrinking spaceprobe

If we wish to emulate Alice and venture far into the garden of interstellar vastness, it may be necessary to shrink our spaceprobes — and possibly even the passengers of later interstellar colonisation ships! We can see the necessity for such drastic measures by investigating kinetic energy requirements for a ‘modest’ interstellar probe.
Latrophilin-2 and latrophilin-3 are redundantly essential for parallel-fiber synapse function in cerebellum

Latrophilin-2 (Lphn2) and latrophilin-3 (Lphn3) are adhesion GPCRs that serve as postsynaptic recognition molecules in CA1 pyramidal neurons of the hippocampus, where they are localized to distinct dendritic domains and are essential for different sets of excitatory synapses. Here, we studied Lphn2 and Lphn3 in the cerebellum. We show that latrophilins are abundantly and differentially expressed in the cerebellar cortex. Using conditional KO mice, we demonstrate that the Lphn2/3 double-deletion but not the deletion of Lphn2 or Lphn3 alone suppresses parallel-fiber synapses and reduces parallel-fiber synaptic transmission by ~50% without altering release probability. Climbing-fiber synapses, conversely, were unaffected. Even though ~50% of total cerebellar Lphn3 protein is expressed in Bergmann glia, Lphn3 deletion from Bergmann glia did not detectably impair excitatory or inhibitory synaptic transmission. Our studies demonstrate that Lphn2 and Lphn3 are selectively but redundantly required in Purkinje cells for parallel-fiber synapses.
Unmasking Intra-tumoral Heterogeneity and Clonal Evolution in NF1-MPNST

Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%-13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones present within the tumor. In the current study, samples were taken from three distinct areas within a single tumor from a patient with an NF1-MPNST. Whole exome sequencing, RNA sequencing, and copy number analysis were performed on each sample. A blood sample was obtained as a germline DNA control. Distinct mutational signatures were identified in different areas of the tumor as well as significant differences in gene expression among the spatially distinct areas, leading to an understanding of the clonal evolution within this patient. These data suggest that multi-regional sampling may be important for driver gene identification and biomarker development in the future.
Abstract LB-100: Systematic target prioritization and validation from genome-scale loss-of-function screens in large panels of human cancer cell lines

Despite its increasing success and revolutionary impact on clinical oncology, Precision Cancer Medicine still has major roadblocks before it becomes applicable to a large proportion of patients. One such roadblock is the limited number of therapeutic targets available. Indeed, for the vast majority of cancer patients, we either do not know what their specific vulnerabilities are or do not have strategies to precisely target their vulnerabilities. In the Cancer Dependency Map Project (DepMap) at the Broad Institute, we aim to overcome these limitations through the use of genome-scale loss-of-function screens in a large panel of cancer cell lines combined with systematic molecular characterization of these cell lines. To date, we have conducted viability screens with genome-wide RNAi and CRISPR/Cas9 libraries on > 800 cell lines, all of which have also been comprehensively profiled with various omics approaches. In order to systematically identify and prioritize potential therapeutic targets, we created an analytical framework that uses a multifaceted approach to score gene dependencies based on the information extracted from screening outcomes, predictive models of sensitivity from all the genetic and molecular information, and the use of priors. To reproducibly validate the nominated targets, we also developed a toolbox of standardized assays that include confirmation of cell viability effects with orthogonal reagents/read-outs and efficient testing for in vivo efficacy across multiple cancer models. Using this approach, we have identified and validated several promising targets, including the WRN DNA helicase that is selectively essential in cancers with microsatellite instability (MSI). The data, framework, and toolbox developed here can inform the nomination and advancement of promising targets for drug development for Precision Cancer Medicine. Citation Format: Tsukasa Shibue, John M. Krill-Burger, Brenton R. Paolella, Benjamin Gaeta, Adhana Asfaw, Joshua M. Dempster, James M. McFarland, David E. Root, Jesse S. Boehm, Aviad Tsherniak, William C. Hahn, Francisca Vazquez. Systematic target prioritization and validation from genome-scale loss-of-function screens in large panels of human cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-100.
The Last Opera: The Rake’s Progress in the Life of Stravinsky and Sung Drama: by Chandler Carter (Russian Music Studies), Bloomington, IN, Indiana University Press, 2019, 348 pp., $105 (hardback), ISBN 978-0-2530-4157-9; $40 (paper), ISBN 978-0-2530-4158-6

Chandler Carter, Professor of Music at Hofstra University, addresses Igor Stravinsky’s 1951 neo-classical opera The Rake’s Progress in this illuminating exploration encompassing three main parts: t...
G354(P) Experience of using anti-TNF infliximab in paediatric inflammatory bowel disease- single tertiary

Background The BSPGHAN and ESPGHAN 2018 standards on management of IBD advocate optimising the use of biological therapy by correlating infliximab drug and anti-body levels with clinical presentation, and subsequently altering treatment if sub-optimal. We aimed to evaluate the infliximab practice at the Royal Manchester Children’s Hospital (RMCH), United Kingdom against these recently published standards. Methods A retrospective study was performed on patients with IBD who had infliximab drug and antibodies levels measured between Oct-2017 and Oct-2018 at RMCH. We collected data on each patient’s current status including stage of disease, infliximab drug and antibody levels, and changes in management if taken. These results were divided into 3 categories for analysis according to infliximab levels: sub-therapeutic (≤4 ug/ml), medium therapeutic (4–7.9 ug/ml) and high therapeutic (≥8 ug/ml). These were then further divided into negative/low level antibodies (≤20 ug/ml) and high level antibodies (≥ 21 ug/ml) subgroups. Each data set was examined to check for adherence to standards. Results During this 13 month period, 77 patients in total had their infliximab levels checked. 72(94%) of these patients were on the recommended immunosuppressant therapy of azathioprine. Many of these patients had multiple infliximab levels performed during the period generating 136 infliximab levels. Out of the total 136 levels done, 87(64%) were sub-therapeutic. 71(82%) of patients with sub-therapeutic infliximab levels showed non active disease either confirmed with normal inflammatory markers or endoscopic findings suggestive of remission. For the 87 with sub-therapeutic Ievels, there were 59(68%) with negative/low antibodies, 35(60%) of these cases were then managed by increasing their infliximab dose/frequency as advised by the standards. For the remaining 28(32%) in the sub-therapeutic group who had positive antibodies, 25%(7) were switched onto a different biologic as recommended by the standards. However, despite having significant levels of antibodies, 14(50%) of patients in the sub-therapeutic group had their infliximab dose/frequency increased. Conclusions There is extensive variability in the infliximab practice for management of IBD at RMCH when comparing against the BSPGHAN/ESPGHAN standards due to being recently published, emphasising capacity for improvement.
Pointer Attack: Lessons Learned in Computer Concept Gamification

Many early students of computer science struggle with a theoretical understanding of new concepts and their programmatic implementations. However, the difficulties associated with the necessary learning often frustrate newer students. Thus, any educational strategy must be able to both engage and motivate. Based on previous research, we developed a small game to teach undergraduate computer science students about pointers, which are variables that reference computer memory indirectly. We did not find that our attempt at gamification yielded significant improvement in student engagement, learning or motivation, but our experience indicates that future research into a sandbox type game has potential to encourage students to learn independently.
Generalized Newton-Leibniz Formula and the Embedding of the Sobolev Functions into H\"{o}lder Spaces

It is well-known that the embedding of the Sobolev space of weakly differentiable functions into Holder spaces holds if the integrability exponent is higher than the space dimension of the domain. In this paper, the embedding of the Sobolev functions into the Holder spaces is expressed in terms of the minimal weak differentiability requirement independent of the integrability exponent. The proof is based on the generalized Newton-Leibniz formula in the rectangular prism and inductive application of the Sobolev trace embedding results. The particular motivation for the new embedding theorem appears in proving compactness of the family of multilinear interpolations of discrete grid functions arising as solutions of the discretized PDE problems.
Basolateral amygdala corticotropin-releasing factor receptor type 1 regulates context-cocaine memory strength during reconsolidation in a sex-dependent manner.

Abstract The basolateral amygdala (BLA) is a critical brain region for cocaine-memory reconsolidation. Corticotropin-releasing factor receptor type 1 (CRFR1) is densely expressed in the BLA, and CRFR1 stimulation can activate intra-cellular signaling cascades that mediate memory reconsolidation. Hence, we tested the hypothesis that BLA CRFR1 stimulation is necessary and sufficient for cocaine-memory reconsolidation. Using an instrumental model of drug relapse, male and female Sprague-Dawley rats received cocaine self-administration training in a distinct environmental context over 10 days followed by extinction training in a different context over 7 days. Next, rats were re-exposed to the cocaine-paired context for 15 min to initiate cocaine-memory retrieval and destabilization. Immediately or 6 h after this session, the rats received bilateral vehicle, antalarmin (CRFR1 antagonist; 500 ng/hemisphere), or corticotropin-releasing factor (CRF; 0.2, 30 or 500 ng/hemisphere) infusions into the BLA. Resulting changes in drug context-induced cocaine seeking (index of context-cocaine memory strength) were assessed three days later. Female rats self-administered more cocaine infusions and exhibited more extinction responding than males. Intra-BLA antalarmin treatment immediately after memory retrieval (i.e., when cocaine memories were labile), but not 6 h later (i.e., after memory reconsolidation), attenuated drug context-induced cocaine seeking at test independent of sex, relative to vehicle. Conversely, intra-BLA CRF treatment increased this behavior selectively in females, in a U-shaped dose-dependent fashion. In control experiments, a high (behaviorally ineffective) dose of CRF treatment did not reduce BLA CRFR1 cell-surface expression in females. Thus, BLA CRFR1 signaling is necessary and sufficient, in a sex-dependent manner, for regulating cocaine-memory strength.
Genetic methods for deciphering virulence determinants of Mycobacterium tuberculosis.

Publisher Summary This chapter describes the methodologies for directed allelic exchange and transposon mutagenesis, employed by laboratory to engineer mutant strains of Mycobacterium. tuberculosis . Allelic exchange protocols based on plasmid transformation or a recently developed mycobacteriophage delivery system are presented. The chapter also describes the use of the mycobacteriophage delivery system for transposon mutagenesis of Mycobacterium. tuberculosis . The ability to apply molecular genetics to the study of M. tuberculosis only recently became a reality. Efficient methods for DNA transfer, utilizing transformation by electroporation and phage transduction, are now available for the production of defined mutations in M. tuberculosis. The development of these techniques IS impeded by the intrinsic difficulties of working with M. tuberculosis that include slow growth (a generation time of 18-24 hr), biosafety considerations, and a tendency to grow in clumps (making isolation of individual clones problematic).
Development and Growth of the Business Class: Strategic Marketing Implications for the Airline Industry

Abstract Air travel is forecasted to be a strong growth market for the 90s. An annual growth rate of over 4% is being predicted until the end of the century. Comprising 20% of the seats and 40% of the overall revenues, the business travel segment had assumed an important strategic focus within the airline industry. This study looks at the competitive issues involved in meeting the demands of the business traveler, especially in the light of the changing relationships between those who supply the product, those who distribute, and those who use it. With corporate America along with the rest of the world continuing to do more business, but with less travel, this study looks at some of the changes that the airline industry can implement to lure business travelers back. Finally, a model is proposed, which the airlines can use to adopt to the changing needs of the market.
Riboregulation by DsrA RNA: trans‐actions for global economy

DsrA is an 87 nucleotide Escherichia coli RNA with extraordinary regulatory properties. The profound impact of its actions stems from DsrA regulating translation of two global transcription regulators, H-NS and RpoS (sigmas), by sequence-specific RNA-RNA interactions. H-NS is a major nucleoid-structuring and global repressor protein, and RpoS is the stationary phase and stress response sigma factor of RNA polymerase. DsrA changes its conformation to bind to these two different mRNA targets and thereby inhibits H-NS translation, while stimulating that of RpoS in a mechanistically distinct fashion. DsrA apparently binds both the start and the stop codons of hns mRNA and sharply decreases the mRNA half-life. DsrA also binds sequences in the 5'-untranslated leader region of rpoS mRNA, enhancing rpoS mRNA stability and RpoS translation. A cohort of genes, governed by H-NS repression and RpoS activation, are thus regulated. Low temperatures increase the levels of DsrA, with differential effects on H-NS and RpoS. Additionally, the RNA chaperone protein Hfq is involved with DsrA regulation, as well as with other small RNAs that also act on RpoS to co-ordinate stress responses. We address the possible functions of this genetic regulatory mechanism, as well as the advantages of using small RNAs as global regulators to orchestrate gene expression.
Can neuroimaging improve the diagnosis and treatment of schizophrenia

Theories of the pathophysiology of schizophrenia suggest that the pathogenesis of the disorder involves irregularities of neurodevelopment that result in distinctive neuroanatomical abnormalities. Among the brain structures involved in such abnormalities are the hippocampus and other components of the limbic system. Because such abnormalities are present before psychotic symptoms develop in patients with schizophrenia, their detection and characterization may be a useful tool for clinicians that are attempting to confirm the psychiatric diagnosis. In an attempt to enrich the types and quality of neuroanatomical information that can be derived from magnetic resonance images, we have recently applied the tools of computational anatomy to the study of selected brain structures in schizophrenia. The shape and symmetry, as well as the volume, of brain structures can be precisely quantified by using such methods. Further, the results of our studies indicate that schizophrenia patients have distinctive abnormalities of the shape and symmetry of the hippocampus and thalamus as compared to controls matched for age, gender and parental socioeconomic status. Also, our results suggest that there is biological heterogeneity among patients with schizophrenia in that some patients can be distinguished from others because they have more distinctive abnormalities of shape in one of these brain areas or the other. The aim of future research will be to add information about additional brain areas to further improve the sensitivity and specificity of neuroanatomical analysis as a potential tool for diagnosis. from International Society on Brain and Behaviour: 1st International Congress on Brain and Behaviour Hyatt Regency Hotel, Thessaloniki, Greece, 20–23 November, 2003
Liquid dispersion in gas—liquid fluidized beds: Part I: Axial dispersion. The axially dispersed plug-flow model

Abstract Axial dispersion coefficients in the liquid phase of gas—liquid (three-phase) fluidized beds have been determined from tracer concentration measurements upstream of the injection plane by using the steady state injection technique and applying the axially dispersed plug-flow model. Water, air and glass beads of 0.45, 0.96, 2 and 3 mm diameter particles were used as the liquid, gas and solid phases, respectively. The superficial velocities ranged from 1.15 to 12.8 cm/s for the liquid phase and from 1.3 to 7 cm/s for the gas phase. The calculated dispersion coefficients increased with increasing gas flow rate and their variation with the liquid flow rate depended on particle size. These coefficients were higher for three-phase fluidized beds than those for the corresponding two-phase particle-free systems. The mixing length decreased with increasing particle size.
Social Capital and Adolescent Well-Being in a National Sample

Abstract Using data from the 1999 National Survey of America's Families (NSAF) on 11,809 boys and girls aged 12 to 17 years, the present study examined measures of adolescent social integration and the availability of community programs against the outcome measures of the Child Behavioral and Emotional Problems Scale (CBEPS) and the Child School Engagement Scale (CSES). On ordinary least squares regression analysis, adolescent participation in an organized activity, the adolescent's not changing schools, and a community program targeting adolescent pregnancy, drugs, or crime were significantly associated with higher scores on both scales. Adolescent employment was associated with a lower CSES score and had no effect on CBEPS. Neither residential stability (years in the home) nor parental religious attendance had any effect on the outcomes, but parental volunteerism was associated with a higher CSES score. The findings may be useful for the design of community programs targeting adolescents in particular b...