cssi/SciSciGPT-SciSciNet huggingface dataset:
WHICH ARE THE LARGEST? WHY LISTS OF MAJOR URBAN AREAS VARY SO GREATLY

Lists of the world's most populous urban areas are surprisingly inconsistent in standard reference sources. These even disagree about which area is the world's largest. We first review the differences found in lists of the 20 largest areas reported by several unofficial sources and by the United Nations. We then demonstrate that variations in the populations and rankings stem mostly from differences in concepts and geographic definitions, and identify six different types of definition in the UN's list. We also offer a set of consistently defined metropolitan areas based on stated guidelines. Case studies for Tokyo, Mexico City, Los Angeles and Beijing include maps to elucidate the administrative areas and statistical definitions in use in each of these urban areas, and illustrate how the varying definitions yield different population totals. We conclude by comparing our consistently defined metropolitan areas with the UN's list of largest urban agglomerations.
The TEXTURE benchmark: measuring performance of text queries on a relational DBMS

We introduce a benchmark called TEXTURE (TEXT Under RElations) to measure the relative strengths and weaknesses of combining text processing with a relational workload in an RDBMS. While the well-known TREC benchmarks focus on quality, we focus on efficiency. TEXTURE is a micro-benchmark for query workloads, and considers two central text support issues that previous benchmarks did not: (1) queries with relevance ranking, rather than those that just compute all answers, and (2) a richer mix of text and relational processing, reflecting the trend toward seamless integration. In developing this benchmark, we had to address the problem of generating large text collections that reflected the (performance) characteristics of a given "seed" collection; this is essential for a controlled study of specific data characteristics and their effects on performance. In addition to presenting the benchmark, with performance numbers for three commercial DBMSs, we present and validate a synthetic generator for populating text fields.
Liver apoptosis is age dependent and is reduced by activation of peroxisome proliferator-activated receptor-γ in hemorrhagic shock

A clinical observation in pediatric and adult intensive care units is that the incidence of multiple organ failure in pediatric trauma victims is lower than in adult patients. However, the molecular mechanisms are not yet defined. Recent experimental studies have shown that the nuclear peroxisome proliferator-activated receptor-γ (PPARγ) modulates the inflammatory process. In this study, we hypothesized that severity of liver injury may be age dependent and PPARγ activation may provide beneficial effects. Hemorrhagic shock was induced in anesthetized young (3–5 mo old) and mature male Wistar rats (11–13 mo old) by withdrawing blood to a mean arterial blood pressure of 50 mmHg. After 3 h, rats were rapidly resuscitated with shed blood. Animals were euthanized 3 h after resuscitation. In mature rats, liver injury appeared more pronounced compared with young rats and was characterized by marked hepatocyte apoptosis, extravasation of erythrocytes, and accumulation of neutrophils. The ratio between the antiapoptotic protein Bcl-2 and the proapoptotic protein BAX was lower, whereas activity of caspase-3, the executioner of apoptosis, was higher in liver of mature rats compared with young rats. Plasma alanine aminotransferase levels were not different between the two age groups. This heightened liver apoptosis was associated with a significant downregulation of PPARγ DNA binding in mature rats compared with young rats. Treatment with the PPARγ ligand ciglitazone significantly reduced liver apoptosis in mature rats. Our data suggest that liver injury after severe hemorrhage is age dependent and PPARγ activation is a novel hepatoprotective mechanism.
Somatic gene therapy for cystic fibrosis

There is considerable potential to ameliorate the pulmonary disease in cystic fibrosis (CF) using somatic gene therapy. Even low levels of expression of the gene in airways epithelium may be beneficial. Adenoviral vectors, DNA-liposome complexes, adeno-associated viral vectors and DNA-ligand complexes have been used effectively in vitro and have been tested in animals to varying extent. Adenoviral vectors and DNA-liposome complexes are being used to deliver the CF gene to patient airways in phase I clinical trials. Transient correction of the electrophysiological defect in human CF nasal epithelium has been achieved. Major goals are (i) to demonstrate that expression of the CF gene in airways epithelium will ameliorate lung disease in CF patients, and (ii) to achieve long-term expression of the introduced gene either through a single delivery with persistent expression or through the ability to use a delivery system repetitively with safety and efficacy.
Modeling the biological control of an alien predator to protect island species from extinction

Introduced feral cat (Felis catus) populations are an important threat to many island vertebrate populations and to bird species in particular. Elimination of feral cat populations is desirable in most of these ecosystems. Release of a parasite species in these mostly immune-naive populations is thought to be an efficient eradication measure. Such an approach is theoretically investigated here, using a mathematical model that describes the effects of introducing a virus into the cat population on population dynamics of both the cat and its prey. We studied the effects of two types of introduced feline viruses: Feline Immunodeficiency Virus and Feline Leukemia Virus, both of which are good candidates for eradicating a cat population. Results show that eradication is possible with Feline Leukemia Virus, if natural immunity is sufficiently low. Feline Immunodeficiency Virus cannot fully eradicate cat populations, but can be an effective agent for long-term control of cat populations on islands where total cat eradication is not possible (e.g., there is a high likelihood of continued introduction of cats) or not desirable (e.g., when rats are present). Culling, which by itself would require a very prolonged and logistically demanding effort to eliminate cat populations, may be more efficient when applied simultaneously with virus introduction.
End-to-end attraction of duplex DNA

Recent experiments [Nakata, M. et al., End-to-end stacking and liquid crystal condensation of 6 to 20 basepair DNA duplexes. Science 2007; 318:1276–1279] have demonstrated spontaneous end-to-end association of short duplex DNA fragments into long rod-like structures. By means of extensive all-atom molecular dynamic simulations, we characterized end-to-end interactions of duplex DNA, quantitatively describing the forces, free energy and kinetics of the end-to-end association process. We found short DNA duplexes to spontaneously aggregate end-to-end when axially aligned in a small volume of monovalent electrolyte. It was observed that electrostatic repulsion of 5′-phosphoryl groups promoted the formation of aggregates in a conformation similar to the B-form DNA double helix. Application of an external force revealed that rupture of the end-to-end assembly occurs by the shearing of the terminal base pairs. The standard binding free energy and the kinetic rates of end-to-end association and dissociation processes were estimated using two complementary methods: umbrella sampling simulations of two DNA fragments and direct observation of the aggregation process in a system containing 458 DNA fragments. We found the end-to-end force to be short range, attractive, hydrophobic and only weakly dependent on the ion concentration. The relation between the stacking free energy and end-to-end attraction is discussed as well as possible roles of the end-to-end interaction in biological and nanotechnological systems.
Decreased sensitivity of NMDA receptors on dopaminergic neurons from the posterior ventral tegmental area following chronic nondependent alcohol consumption.

Background The mesocorticolimbic dopamine system mediates the reinforcing effects of salient stimuli, including drugs of abuse. Nondependent chronic alcohol consumption modifies this system, resulting in an increased number of spontaneously active dopamine neurons in the posterior ventral tegmental area (VTA) of alcohol-preferring (P) rats. Enhanced responses of postsynaptic glutamate receptors may contribute to the increase in active dopamine neurons. Thus, excitations of putative dopamine neurons to locally applied N-methyl-d-aspartic acid (NMDA; glutamate receptor subtype agonist) were evaluated. Methods P rats were assigned to alcohol naive (water only) or alcohol drinking (continuous access to 15% alcohol and water for 8 consecutive weeks) groups. Responses of 23 putative dopamine neurons from naive rats and 19 putative dopamine neurons from drinking rats were assessed in vivo using microiontophoretically applied NMDA. Current–response curves for firing frequency and burst activity were constructed using nonlinear mixed effects models. Between-group comparisons were made for EC50 (effective current producing a half maximal excitatory response), Emax (maximal excitatory effect), and CDB (the current at which depolarization block—marked decrease in neuronal activity—occurred). Results Drinking P rats steadily consumed alcohol over the 8-week protocol and did not exhibit signs of dependence or withdrawal. Putative dopamine neurons from drinking rats exhibited resistance to depolarization block (higher CDB values) and required larger doses of NMDA to elicit moderate excitatory responses (higher EC50 values), consistent with decreased receptor affinity. Maximal excitatory responses (Emax) did not differ between the groups, consistent with no change in receptor number. Blood alcohol was at undetectable levels at the time of experimentation. Conclusions NMDA receptor sensitivity is decreased on posterior VTA putative dopamine neurons in P rats on a nondependent schedule of alcohol consumption. Mechanisms underlying increased spontaneous dopamine neuron activity may be independent of changes in NMDA receptor function. Decreased NMDA receptor sensitivity may precede the development of dependence.
Gender differences in the determinants of distress, alcohol misuse, and related psychiatric disorders

This study examines why women exhibit higher rates of psychological distress and affective and anxiety disorders whereas men report more problems with alcohol and alcohol-related disorders. Using two waves of panel data from 5,001 respondents to the National Co-morbidity Survey, confirmatory factor analysis and structural equation modeling are utilized to compare the stress process of distress, alcohol misuse, and meeting the diagnostic criteria for affective, anxiety, and alcohol-related disorders according to access to resources and exposure to stressors. Theories of emotional socialization, self-salience, and gender roles are applied to interpret gender differences in the determinants of mental health outcomes. The results reveal that gender role theory fits best for models of psychological distress and affective and anxiety disorders, whereas emotional socialization and self-salience theories fit best for models of alcohol intake and alcohol-related disorders.The implications of these resultsand directions for future research on genderdifferences in mental health are discussed.
Larvicidal activity of sterol carrier protein-2 inhibitor in four species of mosquitoes.

A previous report has shown that mosquito sterol carrier protein-2 inhibitors (SCPIs) are larvicidal to larvae of the yellowfever mosquito, Aedes aegypti (L.) (J. Lipid Res. 46: 650–657, 2005). In the current study, we tested SCPI-1 in an additional four mosquito species for larvicidal activities: Culex pipiens pipiens, Anopheles gambiae, Culex restuans, and Aedes vexans. Cholesterol accumulation in SCPI-treated Ae. aegypti fourth instars was examined. SCPI-1 is lethal to all tested mosquito species, with the LC50 value ranging from 5.2 to 15 μM when treatments started at the first to third instar. However, LC50 values increase to from 5.2 to 38.7 μM in treatments started at first and fourth instar, respectively. The results indicate that the lethal effect of SCPI-1 decreases with the growth of larvae, which suggests that SCPI-1 is more effective before the larvae reach final growth period (the last instar). SCPI-1 suppressed cholesterol uptake in Ae. aegypti fourth instars, suggesting that one of the modes of action of SCPI-1 is via reduction in cholesterol absorption.
A Proposed Mechanoreceptor Role for the Small Redundant Muscles which Act in Parallel with Large Prime-Movers

Small, apparently redundant, muscles frequently act in parallel with vastly larger prime-movers and we call this morphological entity the “parallel muscle combination” (PMC). The small muscles of PMCs have much higher muscle spindle densities than their large counterparts, and we call the ratio of mean spindle density of the small muscle/s to that of the large muscle/s in a PMC, the PMC SPINDLE RATIO (PMC-SR). In view of this characteristic of PMCs we proposed that the small muscles thereof play a primarily proprioceptive role (Peck et al., 1984).
Conductivity of Porous Ni / ZrO2 ‐ Y 2 O 3 Cermets

The conductivity of porous Ni/ZrO/sub 2-/Y/sub 2/O/sub 3/ cermets at 1000/sup 0/C was determined as a function of Ni content between 15 and 50 volume percent (v/o) of total solids for two different zirconia particle sizes (23 and 47 m/sup 2//g). Below Ni contents of 30 v/o, ionic conduction through the zirconia phase dominated. At 30 v/o Ni, a greater than three order of magnitude increase in the conductivity was observed, corresponding to a change in mechanism to electronic conduction through the Ni phase. The conductivity of cermets made with a Ni content greater than 30 v/o Ni was found to decrease with increasing temperature between 700/sup 0/ and 1000/sup 0/C. While the conductivity of the cermets with the larger particle size zirconia was higher by more than a factor of four, all the samples studied had the same activation energy, 5.7 +- 0.1 kJ/mol. The increase in conductivity with zirconia particle size is attributed to improved Ni particle-to-particle contact, resulting from the Ni phase being able to cover more completely the surface of the zirconia matrix where it resides.
What was History?: The origins of the ars historica : a question mal posée?

The English mathematician, magus, and antiquary John Dee did many things in a distinctive way. Most distinctive of all, of course, and most effectively ridiculed by Meric Casaubon and many others, was his habit of talking with angels. Dee did this with the help of scryers like Edward Kelly – a gentleman of ill repute who not only saw the celestial beings appear in the show stone that Dee rested on a great seal of wax, but asked one of them, Madini, to lend him a hundred pounds. But when Dee set himself to read works of history, as he often did, he strictly followed standard practices. The Latin prose narratives of Troy's fall by Dares and Dictys – supposedly eyewitness accounts, the former written by a Trojan, but actually late works that circulated in Latin – fascinated Dee as they did many others. Nonetheless, he took care to establish their credibility. Dictys remarked that he could describe what Ulysses did at Troy “very precisely” because he himself had been present. Dee made an immediate inference: autopsy guaranteed authority. “The truth of this account,” he wrote in the margin, “is certain.” Dictys named heroes by their fathers' names as well as their own. Dee firmly believed, as so many of his countrymen did, that the British were descended from the Trojan Brutus. He used a second widely held principle to confirm the authority of his text. Each people had a fairly stable national character or “genius.” Scholars, accordingly, could use modern evidence to confirm and elucidate ancient accounts of a given people: “Note in this passage,” Dee remarked, “the British custom of naming by citing the patronymic or matronymic or both.”
Toward Détente in Immigration Federalism

In its efforts to enforce immigration law, the federal government has been challenged from two directions — by states and localities that regard federal enforcement as feckless and by those that consider it to be overzealous. Spurred in part by social movements, as well as interest group politics, state and local jurisdictions have enacted laws and adopted administrative policies designed to either shift or augment federal enforcement efforts. In previous work, I have emphasized the value of this sort of disharmony, even in areas where federal control or primacy might seem desirable or necessary. Indeed, this churning has forced the federal government to reconceptualize and crystallize its power and priorities. In this essay for the symposium celebrating the work and career of David Martin, however, I argue that the time has come for detente in enforcement federalism, by which I mean renewed prioritization of values of comity and cooperation rather than hierarchy and resistance. After exploring what each level of government stands to gain from a detente, regardless of its views about the propriety and scope of immigration enforcement, I consider what a detente might entail. Despite certain federalizing moves in recent years — the Supreme Court’s decision constraining what pro-enforcement localities might do in Arizona v. United States and the Obama administration’s reformulation of the Secure Communities program, for example — state and local police remain connected and integral to the system of immigration enforcement. The federal government has come to some terms with the views of states and localities, both through its emphasis on the value of cooperation throughout the Arizona litigation and through recent reform of its detainer policies. States and localities and their allies (whether pro or anti-enforcement) ought to do the same, in the interest of creating a well functioning and integrated regime of immigration enforcement sensitive to the communities it polices.
Factors Contributing to Background Television Exposure in Low-Income Mexican-American Preschoolers.

Objective Background television (TV) exposure is harmful to young children, yet few studies have focused on predictors of exposure. This study's objectives were to elucidate demographic, environmental, and behavioral correlates of background TV exposure in low-income Mexican-American preschoolers and to explore caregiver beliefs about the impact of such exposure. Methods A convenience sample of low-income Mexican-American female primary caregivers of preschoolers (3-5 years old, n = 309), recruited in safety-net clinics, were surveyed by phone. Caregivers reported the frequency of their child's exposure to background TV and responded to questions on the home media environment, TV use, and whether they had thought about background TV exposure and its impact on their child. Results Background TV exposure was common; 43 % reported that their child was often, very often, or always exposed to background TV. More hours of TV viewing by the caregiver and greater frequency of TV viewing during meals were associated with an increased frequency of exposure to background TV. Only 49 % of participants had ever thought about the impact of background TV. Believing that background TV is not harmful was associated with higher levels of background TV exposure. Conclusions Findings suggest that background TV exposure is frequent and caregiver awareness of its potential impact is low in low-income Mexican-American families. Beliefs that background TV is not harmful may predict risk of exposure. Potential targets for interventions focused on reducing background TV exposure in this population include increasing caregiver awareness of the potential negative impact of such TV exposure.
Vitamin D supplementation in the ICU patient.

Purpose of reviewRecent findings suggest that vitamin D is a marker for outcomes in critical illness. The purpose of this review is to summarize current biological, observational and interventional evidence in the critically ill.Recent findingsBoth biological and observational studies support the ro
Reward Type and Management Control: An Examination of Organizational Wellness Programs

We examine management control systems in the context of wellness programs — organizational initiatives designed to improve the physical and mental health of employees. In a field study setting, we examine the associations of three different types of incentives (cash, gift cards, and tangible rewards) with reward selection and wellness program performance. We find that employees choose to be rewarded most often with cash, followed by gift cards and tangible rewards, respectively. We find that program participants’ performance is greatest when their chosen reward is a gift card, despite cash rewards being selected more than twice as often. Tangible rewards are the least frequently selected and are associated with lower performance than gift cards but relatively similar performance as cash. These results support theories of individual choice and motivation, and suggest that employees’ incentive choices are not necessarily those with the strongest motivational power.
State Power: Rethinking the Role of the State in Political Corporate Social Responsibility

Key accomplishments of political corporate social responsibility (CSR) scholarship have been the identification of global governance gaps and a proposal how to tackle them. Political CSR scholarship assumes that the traditional roles of state and business have eroded, with states losing power and business gaining power in a globalized world. Consequently, the future of CSR lies in political CSR with new global governance forms which are organized by mainly non-state actors. The objective of the paper is to deepen our understanding of political CSR and reintegrate notions of state power into political CSR scholarship by highlighting how states (1) set the context within which business takes place, (2) regulate offshore business practices, and (3) play pivotal roles in new global governance mechanisms.
A Review of Dose Finding Methods and Theory

In this article, we review the statistical methods and theory for dose finding in early phase clinical trials, where the primary objective is to identify an acceptable dose for further clinical investigation. The dose finding literature is initially motivated by applications in phase I clinical trials, in which dose finding is often formulated as a percentile estimation problem. We will present some important phase I methods and give an update on new theoretical developments since a recent review by Cheung (2010), with an aim to cover a broader class of dose finding problems and to illustrate how the general dose finding theory may be applied to evaluate and improve a method. Specifically, we will illustrate theoretical techniques with some numerical results in the context of a phase I/II study that uses trinary toxicity/efficacy outcomes as basis of dose finding.
Extending nanoscale spectroscopy with titanium nitride probes

We present a means of controlling the stoichiometry of titanium nitride (TiN) coatings on probes for tip-enhanced Raman spectroscopy measurements made using sputtering so that outstanding enhancements can be obtained. This provides a more robust alternative to gold-coated tips that also has potential for tuning the plasmon resonance and working in new environments. Proof of concept measurements on poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) thin films demonstrate increases in the observed intensity with contrast values up to 3.1. TiN is mechanically, chemically, and thermally robust. When deposited under appropriate conditions it has optical properties, including a plasmon resonance, very similar to those of gold. However, the spontaneous formation of a surface TiNxOy layer with relatively high values of y has prevented attaining enhancements in tip-enhanced Raman spectroscopy beyond that provided by the lightning rod effect. Depositing a thin layer of aluminum to form a passivating Al2O3 layer over the TiN plasmonic structure allows the stoichiometry achieved in the vacuum deposition to be maintained. Copyright © 2016 John Wiley & Sons, Ltd.
How to Assess Your CURE: A Practical Guide for Instructors of Course-Based Undergraduate Research Experiences.

Integrating research experiences into undergraduate life sciences curricula in the form of course-based undergraduate research experiences (CUREs) can meet national calls for education reform by giving students the chance to “do science.” In this article, we provide a step-by-step practical guide to help instructors assess their CUREs using best practices in assessment. We recommend that instructors first identify their anticipated CURE learning outcomes, then work to identify an assessment instrument that aligns to those learning outcomes and critically evaluate the results from their course assessment. To aid instructors in becoming aware of what instruments have been developed, we have also synthesized a table of “off-the-shelf” assessment instruments that instructors could use to assess their own CUREs. However, we acknowledge that each CURE is unique and instructors may expect specific learning outcomes that cannot be assessed using existing assessment instruments, so we recommend that instructors consider developing their own assessments that are tightly aligned to the context of their CURE.
Chapter 5 – The Genomic Landscape of Cancers

The main goals of illustrating the cancer genomic landscape are to identify common gene mutations and profile genetic signatures for specific types or stages of cancer. However, the biggest finding is the overwhelming genetic/nongenetic heterogeneity in cancer, reflected in landscapes of gene mutations, epigenomic changes, genome/karyotype alterations, and somatic copy number variations. To promote the integration of these different landscapes, the genome theory of somatic cell evolution is briefly discussed, which redefines the concept of the genome, and links genome-mediated genomic coding to system inheritance or blueprint. The multiple-level landscape model is introduced following the description of punctuated cancer evolution, the relationship of evolutionary phase transition and genome instability, the importance of fuzzy inheritance in heterogeneity, and the mechanism of cancer as an emergent system with different genomes. Micro- and macroevolution are related to gene/epigene and genome evolutions, respectively, and it is thus important to compare the patterns and principles of cancer and organismal evolution.
PENGELOLAAN ADMINISTRASI DOKUMEN PERKANTORANDENGAN ARSIP ELEKTRONIK PADA PT. INFOMEDIA NUSANTARA JAKARTA

Documents administrative management at PT. Infomedia Nusantara is not optimal, where the level of increasing mails volume continuously lead to the equipment and the available storage can no longer accommodate the document. This matter led to the office space look narrower due to the lifting up of the documents.Effects of the accumulation of this document are causing problems. Including the search process documents take a long time because there are so many bundles of documents are untidy.This problem also makes document’s officer hardly to find it. Sometime slipped documents are considered lost. Moreover, the documents are important.Electronic archive applications is a file storage application in electronic form (soft copy), this application is made and can be expected to become solutions. The application is created by web-based, so as to accessible by officers who have been granted access rights in accordance with their duty. Within web-based electronic filing system is expected to make PT.Infomedia Nusantara administrativelyin order, because it will save document storage, enabling archiving, retrieval and distribution of documents, avoiding the uncontrolled destruction of documents and document access rights of the people are not responsible, because with the use of user code and password for each user the appropriate access rights each of the track record of each document can be monitored. In addition to the management and communication processes within the organization will be more effective and efficient. Keyword: Managements, Documents, Administrative
Abstract 16736: The Long Intergenic Non-coding RNA Landscape in Human Macrophage Activation

Introduction: With remarkable plasticity and wide-ranging states of activation in response to environmental challenges, macrophages play a central role in pathogenesis of cardiometabolic diseases (CMDs). However, the long non-coding RNA landscape that regulates macrophage activation is poorly defined. Hypothesis: Comprehensive analysis of long intergenic non-coding RNA (lincRNA) expression profiles reveals novel macrophage lincRNA signature. Methods: We used deep RNA sequencing to assemble the lincRNA transcriptome in human macrophages (HMDM, N=6 subjects) at rest and also after stimulation with lipopolysaccharide and interferon-gamma for M1-like inflammatory activation, and interleukin-4 for M2-like anti-inflammatory activation (A). Results: Through de novo assembly, we identified 2,766 macrophage lincRNAs including 861 previously unannotated novel lincRNAs. The majority (86%) was non-syntenic, or syntenic but not annotated in mouse genomes (B). Many macrophage lincRNAs also demonstrated tissue-enriched transcription patterns (12 %) and enhancer-like chromatin signatures (62 %). Macrophage activation, particularly to the M1 phenotype, markedly altered the lincRNA expression profiles with 96 lincRNAs differentially expressed (fold-change > 2 and FDR Conclusion: In summary, high-resolution transcriptomics identified 100s of lincRNAs that form part of the cellular response in macrophage activation as well as specific macrophage lincRNAs associated with human CMDs.
The incidence and risk factors associated with developing symptoms of hypoglycemia after bariatric surgery

Abstract Background Hypoglycemia after bariatric surgery is an increasingly recognized metabolic complication associated with exaggerated secretion of insulin and gut hormones. Objective We sought to determine the incidence of hypoglycemic symptoms (hypo-sx) after bariatric surgery and characteristics of those affected compared with those unaffected. Setting University hospital. Methods We collected retrospective survey data from the patients who underwent bariatric surgery at a single center. Based on number and severity of postprandial hypo-sx in Edinburgh hypoglycemia questionnaire postoperatively, patients without preoperative hypo-sx were grouped into high versus low suspicion for hypoglycemia. We used multivariable logistic regression to examine potential baseline and operative risk factors for the development of hypo-sx after surgery. Results Among the 1119 patients who had undergone bariatric surgery who received the questionnaire, 464 (40.6%) responded. Among the 341 respondents without preexisting hypo-sx, 29% (n = 99) had new-onset hypo-sx, and most were severe cases (n = 92) with neuroglycopenic symptoms. Compared with the low suspicion group, the high suspicion group consisted of more female patients, younger patients, patients without diabetes, and those who underwent Roux-en-Y gastric bypass with a longer time since surgery and more weight loss. In multivariate analysis, factors independently associated with incidence of hypo-sx after bariatric surgery were female sex (P = .003), Roux-en-Y gastric bypass (P = .001), and absence of preexisting diabetes (P = .011). Conclusions New onset postprandial hypoglycemic symptoms after bariatric surgery are common, affecting up to a third of those who underwent bariatric surgery. Many affected individuals reported neuroglycopenic symptoms and were more likely to be female and nondiabetic and to have undergone Roux-en-Y gastric bypass.
Activation and injury of endothelial cells by cytokines.

Vascular endothelial cells (EC) are primary cellular targets for the actions of pro-inflammatory cytokines such as tumor necrosis factor (TNF). We have studied the signaling pathways used by TNF that lead to new gene expression (endothelial cell activation) or apoptosis (endothelial cell injury). Both responses are initiated by ligand binding to TNFR-I (the p55 receptor). TNF initiates transcription of the E-selectin gene by activation of the transcription factors NF-kappa B and c-Jun/ATF-2. NF-kappa B is activated following degradation of I kappa B alpha and I kappa B-beta. Activation of c-Jun/ATF-2 involves new c-Jun synthesis, and more importantly, phosphorylation of the amino terminus of c-Jun by Jun N-terminal kinase (JNK). Studies in transiently transfected human umbilical vein endothelial cells have revealed that NF-kappa B activation is initiated through the adaptor protein TRAF-2. The activation of JNK also depends upon TRAF-2 and probably involves a kinase cascade initiated by the small G proteins Rac-1 and/or cdc-42. Normally, TNF does not injure human EC. However, TNF can cause apoptosis of EC when cells are co-treated with either the protein synthesis inhibitor cycloheximide (CHX) or the lipid mediator ceramide (cer). The pathways leading to apoptosis following treatment with TNF + CHX and TNF + cer are different since only TNF + CHX is blocked by the caspase inhibitors crmA protein or the peptide zVAD.fmk while only TNF + cer is blocked by the anti apoptotic proteins Bcl-2, Bcl-XL or Al. Both pathways may be inhibited by the anti-apoptotic protein A-20. TNF does not cause the liberation of cer in EC, perhaps because of limited expression of neutral sphingomyelinase-activating adaptor protein FAN. These observations suggest that TNF normally acts as an activator of EC but may change from an activator to a killer of EC when combined with agents that release ceramide, such as u.v. irradiation or cytotoxic drugs, or with ceramide mimetics such as lipopolysaccharide. The activation and injury of endothelial cells induced by TNF and other proinflammatory cytokines may underlie the local effects of these mediators in vivo.
Fashionable and Work Shoes from a Nineteenth-Century Boston Privy

In 1993 excavation of a privy at 27/29 Endicott Street in Boston, Massachusetts, yielded fragments of fashionable and work shoes dating from the 1850s to the 1880s. During these years, two household types lived at the house: all females, some of whom may have been prostitutes, from the 1850s to 1867; and a doctor and his family from 1867 to the 1880s. Three shoe features provide clues about shoe construction and the wearers’ class, gender, and occupation: (1) construction methods, apparent in the soles; (2) style, most evident in shoe uppers; and (3) size. Artifacts provide new evidence of a rand, a shoe part found in the sole.
Vitamin E supplementation and stress affect tissue alpha-tocopherol content of beef heifers.

The effect of stress on tissue alpha-tocopherol was investigated in 16 crossbred heifers fed a corn/corn silage-based diet. For 28 d, eight heifers (379 +/- 10 kg BW) received a dietary supplement of 1,000 IU of dl-alpha-tocopheryl acetate, whereas the controls (375 +/- 10 kg BW) received no supplemental vitamin E. Tissue samples of plasma, red blood cells, liver, trapezius, and longissimus muscles and subcutaneous fat immediately dorsal to each muscle were taken on d 1 for determination of alpha-tocopherol concentration. On d 2 through 4 each heifer was restricted to 2.61 kg of grass hay and allowed water. On d 5, 6, and 7 no feed or water was given, 100 IU of ACTH and .0024 mg of epinephrine/kg BW were given every 8 h, and biopsies for alpha-tocopherol content were again taken on d 7. The stress reduced (P < .01) mean BW, increased (P < .01) serum cortisol, creatine kinase, and urea. After stress, supplemental vitamin E reduced (P < .13) the increase in creatine kinase relative to that in heifers not supplemented with vitamin E. Stress also increased (P < .04) serum Se in heifers fortified with the vitamin E. Alpha-tocopherol content of plasma, red blood cells, liver, and subcutaneous fat dorsal to the trapezius muscle was increased (P < .01) by supplemental vitamin E. The stress treatment reduced (P < .01) alpha-tocopherol content of plasma in those fed the vitamin E and increased it (P < .05) in the nonsupplemented vitamin E-deficient heifers. Stress also decreased red blood cell (P < .01) and liver (P < .05) alpha-tocopherol content in cattle supplemented with vitamin E. Tissue alpha-tocopherol concentrations were reduced by stress only when a diet adequate in vitamin E was fed. In addition, in most sampled tissues, stress did not affect alpha-tocopherol concentrations.
Treatment of the Common Epithelial Cancers

Tumors that originate in the surface epithelium and ovarian stroma constitute 75 to 90% of primary ovarian cancers. Only about 8% of these cancers occur in women under the age of 35, but figures indicate that this number may be increasing. Most common epithelial cancers develop in patients between 40 and 60. Nevertheless, the patient is at risk throughout her entire life to develop cancer of the ovary. Conservative surgery is not indicated in this group, nor should it be considered. Treatment consists in an exploratory laparotomy, washings for cytology, scraping biopsy of the diaphragm, total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, appendectomy, sampling of paraaortic and pelvic lymph nodes, and instillation of 32P if it is thought to be indicated. Chemotherapy has been added to the protocol for prophylaxis of stages I and II where the disease has been macroscopically removed and as definitive therapy for stages II and IV.
Enforcing Unique Code Target Property for Control-Flow Integrity

The goal of control-flow integrity (CFI) is to stop control-hijacking attacks by ensuring that each indirect control-flow transfer (ICT) jumps to its legitimate target. However, existing implementations of CFI have fallen short of this goal because their approaches are inaccurate and as a result, the set of allowable targets for an ICT instruction is too large, making illegal jumps possible. In this paper, we propose the Unique Code Target (UCT) property for CFI. Namely, for each invocation of an ICT instruction, there should be one and only one valid target. We develop a prototype called uCFI to enforce this new property. During compilation, uCFI identifies the sensitive instructions that influence ICT and instruments the program to record necessary execution context. At runtime, uCFI monitors the program execution in a different process, and performs points-to analysis by interpreting sensitive instructions using the recorded execution context in a memory safe manner. It checks runtime ICT targets against the analysis results to detect CFI violations. We apply uCFI to SPEC benchmarks and 2 servers (nginx and vsftpd) to evaluate its efficacy of enforcing UCT and its overhead. We also test uCFI against control-hijacking attacks, including 5 real-world exploits, 1 proof of concept COOP attack, and 2 synthesized attacks that bypass existing defenses. The results show that uCFI strictly enforces the UCT property for protected programs, successfully detects all attacks, and introduces less than 10% performance overhead.
A single seizure selectively impairs hippocampal-dependent memory and is associated with alterations in PI3K/Akt/mTOR and FMRP signaling.

Objective A single brief seizure before learning leads to spatial and contextual memory impairment in rodents without chronic epilepsy. These results suggest that memory can be impacted by seizure activity in the absence of epilepsy pathology. In this study, we investigated the types of memory affected by a seizure and the time course of impairment. We also examined alterations to mammalian target of rapamycin (mTOR) and fragile X mental retardation protein (FMRP) signaling, which modulate elements of the synapse and may underlie impairment. Methods We induced a single seizure and investigated hippocampal and nonhippocampal memory using trace fear conditioning, novel object recognition (NOR), and accelerating rotarod to determine the specificity of impairment in mice. We used western blot analysis to examine for changes to cellular signaling and synaptic proteins 1 h, 24 h, and 1 week after a seizure. We also included a histologic examination to determine if cell loss or gross lesions might alternatively explain memory deficits. Results Behavioral results indicated that a seizure before learning leads to impairment of trace fear memory that worsens over time. In contrast, nonhippocampal memory was unaffected by a seizure in the NOR and rotarod tasks. Western analysis indicated increased hippocampal phospho-S6 and total FMRP 1 h following a seizure. Tissue taken 24 h after a seizure indicated increased hippocampal GluA1, suggesting increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression. Histologic analysis indicated that neither cell loss nor lesions are present after a single seizure. Significance The presence of memory impairment in the absence of damage suggests that memory impairment caused by seizure activity differs from general memory impairment in epilepsy. Instead, memory impairment after a single seizure is associated with alterations to mTOR and FMRP signaling, which leads to a disruption of synaptic proteins involved in consolidation of long-term memory. These results have implications for understanding memory impairment in epilepsy.
Predicting deviations in software execution paths due to EMI injection via reachable sets and random delays

We describe the process of calculating reachable sets for the dynamics of a hybrid model of logic gates. We then use this framework to estimate the impact of electromagnetic interference on the execution of a segment of code. We consider temporal changes as well as changes to the initial conditions in the logic gates, and we consider their impact on the intended software execution.
Current quality gaps in rectal cancer pathology reports.

6581 Background: High-quality pathology reporting is important for optimal management of rectal cancer (RC). To this end, several quality measures have been clinically validated or endorsed by the ...
Topological Hall effect and emergent skyrmion crystal at manganite-iridate oxide interfaces

The competition between the Dzyaloshinskii-Moriya interaction and magnetic exchange interactions is known to create exotic spin textures such as spin-spiral and skyrmion-crystal phases. Using Monte Carlo simulations, this work explores novel magnetic textures at the interface between two perovskite oxides, strontium iridate and lanthanum manganite, where the double-exchange hopping and the Dzyaloshinskii-Moriya interaction coexist. The formation of various possible noncollinear spin textures at the interface as a function of temperature and applied magnetic field as well as the emergent topological Hall effect in the skyrmion crystal phase are revealed.
Personalizing dosing of risperidone, paliperidone and clozapine using therapeutic drug monitoring and pharmacogenetics

Abstract By combining knowledge of pharmacogenetics, therapeutic drug monitoring (TDM) and drug-drug interactions (DDIs) the author developed a model for personalizing antipsychotic dosing, which is applied to risperidone, 9-hydroxyrisperidone or paliperidone, and clozapine. Drugs are approved using an average dose for an ideal average patient, but pharmacologists have described outliers: genetic poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Environmental and personal variables can also make patients behave as PMs or UMs. Drug clearance is represented by the concentration-to-dose (C/D) ratio under steady-state and trough conditions. A very low C/D ratio indicates a UM, while a very high C/D ratio indicates a PM. Total risperidone C/D ratio for the oral formulation is around 7 ng/ml per mg/day and can be influenced by CYP2D6 polymorphism, DDIs with inducers and inhibitors, and renal function. Oral paliperidone has low availability; its C/D ratio is around 4.1 ng/ml per mg/d and can be influenced by inducers and renal impairment. Once-a-month long-acting paliperidone provides a C/D ratio around 7.7 ng/ml per mg/day at steady state, which is expected to be in the 8th month (before the 9th injection). TDM is particularly important for long-acting paliperidone formulations that may accumulate once steady state is reached (after years for the 3- and 6-month formulations). In the US, clozapine C/D ratios typically range from 0.6 (male smokers) to 1.2 (female non-smokers) ng/ml per mg/day. East Asians’ clozapine C/D ratios appear to be twice as high. Inhibitors (including fluvoxamine and oral contraceptives) and inflammation can also increase clozapine C/D ratios. This article is part of the issue entitled ‘Special Issue on Antipsychotics’.
Targeted phosphoproteomics of the Ras signaling network reveal regulatory mechanisms mediated by oncogenic KRAS

Abstract Background KRAS mutations are present in up to 30% of lung adenocarcinoma cases and are associated with poor survival. No effective targeted therapy against KRAS is currently available, and novel strategies to counteract oncogenic KRAS signaling are needed. Results We used targeted proteomics to monitor abundance and site-specific phosphorylation in a network of over 150 upstream and downstream effectors of KRAS signaling in H358 cells (KRAS G12C). We compared patterns of protein regulation following sustained signaling blockade in the RAS/ERK module at two different levels, KRAS and MEK. Network-based analysis demonstrated complex non-linear patterns of regulation with wide-spread crosstalk among diverse subnetworks. Among 85 most regulated proteins in the network, only 12 proteins showed concordant regulation in response to signaling blockade at both KRAS and MEK levels, while the remainder were either specifically regulated in response to KRAS knockdown or MEK inhibition or showed orthogonal regulation in both conditions. Dephosphorylation of DNA methyltransferase 1 (DNMT1) at S714 was identified among the changes unique to KRAS knockdown, and here we elucidate the role of this phosphorylation in KRAS-dependent transcriptional silencing of tumor suppressor genes. Conclusions Network-based analysis of the Ras signaling has shown complex non-linear patterns of regulation with wide-spread crosstalk among diverse subnetworks. Our work illustrates a targeted proteomics approach to functional interrogation of complex signaling networks focused on identification of readily testable hypotheses. These methods are widely applicable to diverse questions in tumor biology and other signaling paradigms.
What Should Be the Role of Social Media in Education

Social media provide new opportunities for when, how, where, and with whom people learn—venue unimaginable 15 years ago. Today’s students and educators have adopted social media for various purpose...