cssi/SciSciGPT-SciSciNet huggingface dataset:
Oral carcinogenesis induced by 4-nitroquinoline 1-oxide in lecithin:retinol acyltransferase gene knockout mice.

Abstract Lecithin:retinol acyltransferase (LRAT) regulates retinol (vitamin A) metabolism by esterifying retinol. LRAT expression is decreased in cultured human squamous cell carcinoma cells of the head and neck relative to normal epithelial cells. We investigated whether the carcinogen 4-nitroquinoline 1-oxide (4-NQO) induced a higher incidence of oral cancer in LRAT knockout (LRAT−/−) than in wild-type (Wt) mice. We also investigated retinol deprivation during 4-NQO treatment in LRAT−/− mice as a model for rapid retinol deficiency. We observed higher levels of secreted frizzled-related protein (Sfrp) 2, an inhibitor of WNT signaling, in tongue tumors in LRAT−/− versus Wt. LRAT−/− embryonic stem cells also expressed higher Sfrp2 transcripts, indicating an interaction between retinol and WNT signaling. Cox-2, Cyclin D1, p21, Trop2 and RARβ2 were not differentially expressed in Wt versus LRAT−/− tongue tumors. Wt and LRAT−/− mice fed a retinol-sufficient diet showed the same oral tumor incidence after 4-NQO treatment. In contrast, tongue tumors developed in 60% of Wt mice and in 100% of LRAT−/− mice fed a retinol-deficient diet during 4-NQO treatment (P=.22); moreover, the bromodeoxyuridine labeling index was 21.0±2.4% in LRAT−/− normal tongue epithelium as compared to 9.9±0.8% in Wt normal tongue epithelium (P
Interprocedural compatibility analysis for static object preallocation

We present an interprocedural and compositional algorithm for finding pairs of compatible allocation sites, which have the property that no object allocated at one site is live at the same time as any object allocated at the other site. If an allocation site is compatible with itself, it is said to be unitary: at most one object allocated at that site is live at any given point in the, execution of the program. We use the results of the analysis to statically preallocate memory space for the objects allocated at unitary sites, thus simplifying the computation of an upper bound on the amount of memory required to execute the program. We also use the analysis to enable objects allocated at several compatible allocation sites to share the same preallocated memory. Our experimental results show that, for our set of Java benchmark programs, 60% of the allocation sites are unitary and can be statically preallocated. Moreover, allowing compatible unitary allocation sites to share the same preallocated memory leads to a 95% reduction in the amount of memory preallocated for these sites.
Computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings in adrenal candidiasis and histoplasmosis: two cases

We report the contrast-enhanced computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography findings in adrenal histoplasmosis and candidiasis. Both demonstrated bilateral hypermetabolic heterogeneous adrenal masses with limited wash-out on delayed CT. Adrenal candidiasis has not been previously reported, nor have the CT wash-out findings in either infection. The adrenal imaging findings are indistinguishable from malignancy, which is more common; but in this setting, physicians should be alert to the differential diagnosis of fungal infections, since it can be equally deadly.
A Man for All Seasons: Reflections on the Life and Legacy of George Palade

In this perspective, I review the scientific career of George E. Palade, the man many consider to be the father of cell biology. Palade's scientific contributions spanned more than 50 years (from the late 1940s to 2001) and were amazingly diverse and fundamental. He is best known for his discovery of ribosomes, for establishing their role in protein synthesis, and for delineation of the secretory pathway. In addition to these groundbreaking contributions, he also developed basic techniques for tissue preservation and cell fractionation that allowed rapid progress during the early days of cell biology, and he and his collaborators provided the first description of the mitochondrial cristae, neuronal synapses, junctional complexes in epithelia, plasmalemmal vesicles, and Weibel-Palade bodies in endothelium, among others. He and his collaborators also contributed key experimental data to our understanding not only of protein synthesis and the secretory process but also of membrane biogenesis and vascular permeability. In addition to his scientific discoveries, he had a profound impact on the lives of many cell biologists and served the scientific community tirelessly while making major contributions to the development of cell biology in three major institutions.
Spousal undermining of older diabetic patients’ disease management

Marriage can enhance health for individuals with a chronic disease, yet spouses may also undermine disease management. The current study investigated spousal undermining of dietary regimen in 129 patients with type 2 diabetes mellitus. A total of 40 patients reported that their spouses tempted them with forbidden foods, and 15 reported that their spouses conveyed disregard for their diabetic diet. Spousal tempting was associated with worse dietary adherence, and spousal disregard with worse nondietary adherence. Spousal undermining is relatively rare but is associated with patients' disease management and warrants further investigation to better understand how spouses influence partners' day-to-day management of chronic diseases.
Raman and infrared spectra, vibrational assignments and barriers to internal rotation of cis‐ and trans‐1‐chloropropene

The Raman spectra of both cis- and trans-1-chloropropene were obtained between 3500 and 20 cm−1 for the vapor, liquid and solid states and the polarization data were obtained for the fluid phases. The infrared spectra were recorded between 3500 and 50 cm−1 for both compounds in the vapor and solid states. Complete vibrational assignments based on depolarization data, infrared band contours and group frequencies are presented for both molecules on the basis of Cs symmetry. The methyl torsion for trans-1-chloropropene was observed in the infrared spectrum of the vapor as a series of transitions with the 1 0 fundamental having a frequency of 208 cm−1; from this fundamental frequency a periodic barrier to internal rotation was calculated to be 844±16 cm−1 (2413±46 cal mol−1). Although the methyl torsion was not observed directly for cis-1-chloropropene, the first overtone was tentatively assigned in the Raman spectrum of the vapor at 205 cm−1. Many of the fundamentals for both the cis and trans molecule appear as doublets in the spectra of the solids which indicates that there are at least two molecules per primitive cell for each solid. These results are compared to corresponding quantities in some similar molecules.
Field Trial of Endotracheal Intubation by Basic EMTs

Abstract Study objective: The 1994 basic-EMT (EMT-B) curriculum recommended teaching EMT-Bs the skill of endotracheal intubation. In this study we assessed the success and complication rates of endotracheal intubations in the field by EMT-Bs. Methods: We conducted a prospective clinical trial over a period of 28 months in an urban out-of-hospital EMS system. Four first-responder EMT-B engine companies with paramedic backup received 10 hours' intubation training in three sessions spread over at least 2 weeks. The training module was similar to that of the 1994 EMT-B curriculum and included at least 10 intubations on manikins. The EMTs used manikins with closed chest cavities to learn assessment of endotracheal-tube placement. Patients were eligible for intubation by the EMTs if they were apneic and older than 15 years. We calculated 95% confidence interval (CIs) for intubation success rates. Results: Sixty-six EMT-Bs passed the training examinations and were authorized to perform intubation in the field. Endotracheal intubation was attempted by EMTs in 103 patients; the attempt was successful in 53 (95% CI, 42% to 61%). All patients who were not intubated by EMT-Bs were intubated by paramedics, with the exception of six cases. One attempt at intubation was made in 52 patients, two attempts in 44, and three in 7. Three unrecognized esophageal intubations occurred. Conclusion: EMT-Bs trained in a short course successfully intubated about half the patients they encountered in this study. This low intubation success rate calls into question the validity of the endotracheal-intubation training module in the 1994 EMT-B national curriculum. [Sayre MR, Sakles JC, Mistler AF, Evans JL, Kramer AT, Pancioli AM: Field trial of endotracheal intubation by basic EMTs. Ann Emerg Med February 1998;31:228-233.]
CA-based Simulation of Asian Urban Dynamics: A Case Study of Taipei Metropolitan Area, Taiwan

The rapid urbanization process in Asia has contributed to a distinctive urban pattern that is different from the West. Though it is believed Asian urbanization process is driven by local activities, some argue globalization also plays a key role in Asian urban dynamics and the distinctive urban pattern. To examine interactions of global/local factors in Asian urban dynamics, this study incorporates remote sensing imagery, GIS technology, and socio-economic data into a CA-based urban model. Taipei metropolitan area, one of the fast growing urban areas in Asia, is selected to examine this model. Our preliminary results indicate that the interaction between local and global processes closely interrelates to drive urban dynamics and shapes the unique urban pattern in Asia.
Preliminary X-ray crystallographic studies of yeast mitochondrial protein Tom70p.

Protein translocations across mitochondrial membranes play critical roles in mitochondrion biogenesis. Protein transport from the cell cytosol to the mitochondrial matrix is carried out by the translocase of the outer membrane (TOM) complex and the translocase of the inner membrane (TIM) complexes. Tom70p is an important TOM-complex member and a major surface receptor of the protein-translocation machinery in the outer mitochondrial membrane. To investigate the mechanism by which Tom70p functions to deliver the mitochondrial protein precursors, the cytosolic fragment of yeast Tom70p (cTom70p) was crystallized. The crystals diffract to 3.2 A using a synchrotron X-­ray source and belong to space group P21, with unit-cell parameters a = 44.89, b = 168.78, c = 83.41 A, α = 90.00, β = 102.74, γ = 90.00°. There are two Tom70p molecules in one asymmetric unit, which corresponds to a solvent content of approximately 51%. Structure determination by MAD methods is under way.
Widespread climate change in the Himalayas and associated changes in local ecosystems.

Background Climate change in the Himalayas, a biodiversity hotspot, home of many sacred landscapes, and the source of eight largest rivers of Asia, is likely to impact the well-being of ∼20% of humanity. However, despite the extraordinary environmental, cultural, and socio-economic importance of the Himalayas, and despite their rapidly increasing ecological degradation, not much is known about actual changes in the two most critical climatic variables: temperature and rainfall. Nor do we know how changes in these parameters might impact the ecosystems including vegetation phenology. Methodology/Principal Findings By analyzing temperature and rainfall data, and NDVI (Normalized Difference Vegetation Index) values from remotely sensed imagery, we report significant changes in temperature, rainfall, and vegetation phenology across the Himalayas between 1982 and 2006. The average annual mean temperature during the 25 year period has increased by 1.5°C with an average increase of 0.06°C yr−1. The average annual precipitation has increased by 163 mm or 6.52 mmyr−1. Since changes in temperature and precipitation are immediately manifested as changes in phenology of local ecosystems, we examined phenological changes in all major ecoregions. The average start of the growing season (SOS) seems to have advanced by 4.7 days or 0.19 days yr−1 and the length of growing season (LOS) appears to have advanced by 4.7 days or 0.19 days yr−1, but there has been no change in the end of the growing season (EOS). There is considerable spatial and seasonal variation in changes in climate and phenological parameters. Conclusions/Significance This is the first time that large scale climatic and phenological changes at the landscape level have been documented for the Himalayas. The rate of warming in the Himalayas is greater than the global average, confirming that the Himalayas are among the regions most vulnerable to climate change.
Improving performance of large physically indexed caches by decoupling memory addresses from cache addresses

Modern CPUs often use large physically indexed caches that are direct-mapped or have low associativities. Such caches do not interact well with virtual memory systems. An improperly placed physical page will end up in a wrong place in the cache, causing excessive conflicts with other cached pages. Page coloring has been proposed to reduce the conflict misses by carefully placing pages in the physical memory. While page coloring works well for some applications, many factors limit its performance. Page coloring limits the freedom of the page placement system and may increase swapping traffic. In this paper, we propose a novel and simple architecture, called color-indexed, physically tagged caches, which can significantly reduce the conflict misses. With some simple modifications to the TLB (translation look-aside buffer), the new architecture decouples the addresses of the cache from the addresses of the main memory. Since the cache addresses do not depend on the the physical memory addresses anymore, the system can freely place data in any cache page to minimize the conflict misses, without affecting the paging system. Extensive trace-driven simulation results show that our design performs much better than traditional page coloring techniques. The new scheme enables a direct-mapped cache to achieve hit ratios very close to or better than those of a two-way set associative cache. Moreover, the architecture does not increase cache access latency, which is a drawback of set associative caches. The hardware overhead is minimal. We show that our scheme can reduce the cache size by 50 percent without sacrificing performance. A two-way set associative cache that uses this strategy can perform very close to a fully associative cache.
Contextualizing Sexual Objectification

The preceding articles provide an excellent overview of relatively recent theory and research on sexual objectification of women from a psychological perspective. Importantly, the authors have contributed to the literature through their conceptual extensions and research applications of objectification theory. In this reaction piece, our goals are to direct attention to an underplayed aspect of objectification theory, offer applause and a caveat about specifying criteria for sexually objectifying environments, critically analyze false parallels and common yes, but challenges to objectification theory, encourage further consideration of sociopolitical dimensions of sexual objectification, and suggest avenues for continued work.
Political Political Theory: An Oxford Inaugural Lecture

This paper was given as an "Inaugural Lecture" for the Chichele Professorship of Social and Political Theory" at Oxford University on May 3, 2012. Political theorists study (1) political virtue, (2) political processes and institutions, and (3) political ideals (like justice, liberty, and equality). Since the time of Hume, Madison, and Kant, it has been thought that (2) is more important than (1), because maybe we can set up institutions that work for the general good whatever the state of virtue of the people who administer them. But in the revival of political philosophy heralded by John Rawls's book in 1971, there has been great emphasis on (3) and not nearly enough emphasis on (2). This is particularly true in the UK. Previous holders of the Chichele chair (G.A. Cohen and Isaiah Berlin) focused almost exclusively on (3) -- with Berlin going so far as to announce that political philosophy was really just the study of "the ends of life." The lecture argues that this way of conceiving the subject-matter of the Chichele chair is at best one-sided.The lecture argues for a reorientation of political theory teaching and scholarship back towards institutions -- particularly the normative evaluation of various aspects of the political process and the detailed theoretical exploration of institutional principles like democracy, representation, bicameralism, the rule of law, the separation of powers, federalism and so on. It argues that these issues should not be left to empirical or comparative politcial science, because they raise important and complex questions of evaluation -- including dignitary evaluation -- that may be sold short by the pragmatic and consequentialist emphasis of empirical and comparative work. But political theory should respect the empirical study of institutions more than it does, and it should dovetail the normative and evaluative work that political theory involves with the understanding of institutions, processes, and practices that political science generates.
Genome-Wide Characterization of the SloR Metalloregulome in Streptococcus mutans

Streptococcus mutans is the primary causative agent of human dental caries, a ubiquitous infectious disease for which effective treatment strategies remain elusive. We investigated a 25-kDa SloR metalloregulatory protein in this oral pathogen, along with its target genes that contribute to cariogenesis. Previous studies have demonstrated manganese- and SloR-dependent repression of the sloABCR metal ion transport operon in S. mutans. In the present study, we demonstrate that S. mutans coordinates this repression with that of certain virulence attributes. Specifically, we noted virulence gene repression in a manganese-containing medium when SloR binds to promoter-proximal sequence palindromes on the S. mutans chromosome. We applied a genome-wide approach to elucidate the sequences to which SloR binds and to reveal additional “class I” genes that are subject to SloR- and manganese-dependent repression. These analyses identified 204 S. mutans genes that are preceded by one or more conserved palindromic SloR recognition elements (SREs). We cross-referenced these genes with those that we had identified previously as SloR and/or manganese modulated in microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) experiments. From this analysis, we identified a number of S. mutans virulence genes that are subject to transcriptional upregulation by SloR and noted that such “class II”-type regulation is dependent on direct SloR binding to promoter-distal SREs. These observations are consistent with a bifunctional role for the SloR metalloregulator and implicate it as a target for the development of therapies aimed at alleviating S. mutans-induced caries formation.
Endogenous CRF in rat large intestine mediates motor and secretory responses to stress.

Background Corticotropin-releasing factor (CRF) mediates our body's overall responses to stress. The role of central CRF in stress-stimulated colonic motility is well characterized. We hypothesized that transient perturbation in expression of enteric CRF is sufficient to change stress-induced colonic motor and secretory responses. Methods Sprague–Dawley rats (adult, male) were subjected to 1-h partial restraint stress (PRS) and euthanized at 0, 4, 8, and 24 h. CRF mRNA and peptide levels in the colon were quantified by real-time RT-PCR, enzyme immuno-assay and immunohistochemistry. Double-stranded RNA (dsRNA) designed to target CRF (dsCRF) was injected into the colonic wall to attain RNA interference-mediated inhibition of CRF mRNA expression. DsRNA for β-globin was used as a control (dsControl). Four days after dsRNA injection, rats were subjected to 1-h PRS. Fecal output was measured. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial tissue conductance. Key Results Exposure to PRS elevated CRF expression and increased CRF release in the rat colon. Injection of dsCRF inhibited basal CRF expression and prevented the PRS-induced increase in CRF expression, whereas CRF expression in dsControl-injected colons remained high after PRS. In rats treated with dsControl, PRS caused a significant increase in fecal pellet output, colonic baseline ion secretion, and transepithelial tissue conductance. Inhibition of CRF expression in the colon prevented PRS-induced increase in fecal output, baseline ion secretion, and transepithelial tissue conductance. Conclusions & Inferences These results provide direct evidence that transient perturbation in peripherally expressed CRF prevents colonic responses to stress.
Earlier activity of Drosophila suzukii in high woodland landscapes but relative abundance is unaffected

Natural habitats can affect the population dynamics of mobile insects, and the spatial and temporal effects on agricultural pest species may be especially relevant for tailoring management strategies to the farm context. Drosophila suzukii Matsumura (Diptera: Drosophilidae) is suspected to utilize woodland habitat for wild hosts and overwintering with possible adverse effects of woods on adjacent fruit crops. A two-year study in the Upper Midwest, USA examined if the amount of woodland in the landscape affects early season activity and relative abundance of D. suzukii in raspberry fields. Thirty-five farms were selected to span a gradient of low-to-high woodland area at the 1.5 km scale. The first capture of D. suzukii occurred earlier at farms in high woodland landscapes. However, woodland area was not correlated with metrics of D. suzukii abundance in raspberry (growth rate, peak, fall, or total fly catch) suggesting similar crop infestation risk across landscapes. However, woodland area was negatively correlated with fall fly catch in the adjacent woods and significantly more flies were captured in the woods than raspberry. This study suggests woodland landscapes affect early season crop risk and the high numbers of D. suzukii in the woods have implications for understanding overwintering.
Fermion Pairing with Unequal Spin Populations

We have produced a two-component gas of ultracold, fermionic 6Li atoms with unequal spin populations. The real-space densities reveal a superfluid/normal phase separation at very low temperatures, and a partially polarized paired phase at higher temperatures.
The Three-Headed EagleThe United States and System Change

It is by now a commonplace observation that the “age of consensus” on questions of foreign policy was a casualty of the American involvement in Vietnam. This article focuses on the resulting domestic cleavages relating to foreign policy issues, and on their likely impact on American efforts to undertake basic systemic changes. The “Three-Headed Eagle” serves as a metaphor for a nation marked by three quite distinctive clusters of beliefs—described here as Cold War Internationalism, Post-Cold War Internationalism, and Isolationism“about the nature of the global system, the sources of threats to a just and stable world order, the appropriate international role for the United States, and the goals, strategies, and tactics that should guide American external relations. Will these cleavages persist? Efforts of the Nixon-Ford and Carter administrations to reestablish a foreign policy consensus, through policies of detente and human rights, have exacerbated rather than healed divisions. Systematic evidence from public opinion and leadership studies also appears to confirm the existence of the cleavages discussed here. Moreover, because the divisions exist within as well as between generations, it is unlikely that the ascendency of a new generation of leadership will automatically create a new foreign policy consensus.
A SYSTEMATIC REVIEW OF PERCUTANEOUS CLOSURE OF RUPTURED SINUS OF VALSALVA ANEURYSM IN ADULTS

Sinus of Valsalva aneurysm (SVA) is a rare anomaly and is mostly congenital. It can rupture into one of the cardiac chambers leading to aorto-cardiac fistula. Urgent repair is recommended to prevent heart failure. Surgical repair with patch closure has been the treatment of choice. Percutaneous
“I Can Defend Myself” Women’s Strategies for Coping With Harassment While Gaming Online

Although video game audiences have greatly diversified over recent years, players who are not the stereotypical straight, White, male “gamer” are still frequently viewed as outsiders to online gaming and face harassment because of this status. However, many choose to play games despite this and have developed specific coping strategies they employ to avoid or respond to harassment. Using grounded theory and in-depth interviews with female gamers, this gender-based case study explores women’s strategies for coping with online game-related harassment. It shows that women are first and foremost an active audience, carefully managing their media environment to help ensure positive experiences. At the same time, their strategies come with limitations, such as hiding their contributions to gaming or provoking further harassment. Although women are capable media managers, their continued status as “outsiders” deeply affects their gaming experiences and demonstrates a need for cultural change in online environments.
Advances in unit testing: theory and practice

Parameterized unit testing, recent advances in unit testing, is a new methodology extending the previous industry practice based on traditional unit tests without parameters. A parameterized unit test (PUT) is simply a test method that takes parameters, calls the code under test, and states assertions. Parameterized unit testing allows the separation of two testing concerns or tasks: the specification of external, black-box behavior (i.e., assertions or specifications) by developers and the generation and selection of internal, white-box test inputs (i.e., high-code-covering test inputs) by tools. PUTs have been supported by various testing frameworks. Various open source and industrial testing tools also exist to generate test inputs for PUTs. This technical briefing presents latest research on principles and techniques, as well as practical considerations to apply parameterized unit testing on real-world programs, highlighting success stories, research and education achievements, and future research directions in developer testing.
3D palaeogeographic reconstructions of the Phanerozoic versus sea-level and Sr-ratio variations: Discussion

Abstract Veacute;rard et al. (2015, Journal of Palaeogeography , 4(1): 64-84) claim that their global geodynamic model allows one to reconstruct the surface features of topography on land and in adjacent oceans (i.e., paleobathymetry) anywhere on the globe and at any geological time during the past 600 million years (Ma). Such a grand model requires a rigorous scrutiny. The purpose of this discussion is to illustrate that the model suffers from (1) the selective omission of real-world datasets that do not fit the model, (2) the inclusion of datasets without revealing their original sources or without citing relevant peer-reviewed publications, (3) the emphasis on ‘unpublished’ internal company datasets that disallow open access to the international scientific community, and (4) the use of poorly understood concepts without providing the basic conceptual clarity. These deficiencies undermine the credibility of the heuristic model.
The Shifting Walls of Separation between Church and State in the United States

This article analyses five distinct understandings of separation of church and state in the American founding era of 1776-1812 and the continued influence and manifestations of each of these five understandings in current American constitutional law. The last section argues that separation of church and state is a valuable constitutional ideal, so long as it is used prudentially not categorically, and so long as it remains balanced with other founding principles of religious freedom.
An Afro-German Microhistory: Gender, Religion, and the Challenges of Diasporic Dwelling

This article traces the biography of an Afro-German woman born during the 1920s Rhineland occupation to examine the peculiarities of the black German diaspora, as well as potential connections between these peculiarities and larger trends in the history of German colonialism and racism. “Erika Diekmann” was born in Worms in 1920. Her mother was a German citizen, her father a Senegalese French soldier. Separated from her birth mother at a young age, Erika spent her youth and early adulthood in a school for Christian Arab girls in Jerusalem run by the Protestant order of the Kaiserswerth Deaconesses (KaiserswertherDiakonissen). After World War II, Erika returned to West Germany, but in 1957, she emigrated to the United States, along with her (white) German husband and four children. Erika's story offers unique opportunities for studying Afro-German women's active strategies of making Germany their “home.” It underlines the complicated role of conventional female gender prescriptions in processes of interracial family-building. The centrality of religion to Erika's social relationships significantly enhances our understanding of the complexity of German attitudes toward national belonging and race during the first half of the twentieth century.
The Darwinian Revolution

All cultures have developed explanations for the origin of the world and human beings. Classical Greece and the monotheistic religions attribute the creation of the world to God, thereby accounting for the design of organisms. Charles Darwin advanced a theory of evolution by natural selection , which accounts for the diversity and adaptation of organisms. Historians of science speak of two scientific revolutions: the Copernican, which removed the Earth from the center of the universe to become one more planet revolving around the Sun; and the Darwinian, which removed humans from being the center of life to become one more animal species . Important as these considerations are, it is more accurate to see these revolutions as the two stages of a single revolution: the beginning of science in the modern sense of the word. Henceforward, the phenomena of the natural universe could be understood as the outcomes of natural processes that could be accounted for by theories and propositions subject to empirical tests by observation and experimentation.
The ethics of persuasive technology

This chapter deals with the ethics of persuasive technology. Ethical issues are especially prominent when computer technology uses novelty as a distraction to increase persuasion. When dealing with a novel experience, people not only lack expertise but they are distracted by the experience, which impedes their ability to focus on the content presented. Being in a novel situation can make people more vulnerable because they are distracted by the newness or complexity of the interaction. When it comes to persuasion, computers also benefit from their traditional reputation of being intelligent and fair, making them seem credible sources of information and advice. Another advantage of computers is persistence. Unlike human persuaders, computers don't get tired; they can implement their persuasive strategies over and over.
Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2′-deoxyguanosine by Human DNA Polymerase η *

O6-Methyl-2′-deoxyguanosine (O6-MeG) is a ubiquitous DNA lesion, formed not only by xenobiotic carcinogens but also by the endogenous methylating agent S-adenosylmethionine. It can introduce mutations during DNA replication, with different DNA polymerases displaying different ratios of correct or incorrect incorporation opposite this nucleoside. Of the "translesion" Y-family human DNA polymerases (hpols), hpol η is most efficient in incorporating equal numbers of correct and incorrect C and T bases. However, the mechanistic basis for this specific yet indiscriminate activity is not known. To explore this question, we report biochemical and structural analysis of the catalytic core of hpol η. Activity assays showed the truncated form displayed similar misincorporation properties as the full-length enzyme, incorporating C and T equally and extending from both. X-ray crystal structures of both dC and dT paired with O6-MeG were solved in both insertion and extension modes. The structures revealed a Watson-Crick-like pairing between O6-MeG and 2"-deoxythymidine-5"-[(α, β)-imido]triphosphate (approximating dT) at both the insertion and extension stages with formation of two H-bonds. Conversely, both the structures with O6- MeG opposite dCTP and dC display sheared configuration of base pairs but to different degrees, with formation of two bifurcated H-bonds and two single H-bonds in the structures trapped in the insertion and extension states, respectively. The structural data are consistent with the observed tendency of hpol η to insert both dC and dT opposite the O6-MeG lesion with similar efficiencies. Comparison of the hpol η active site configurations with either O6-MeG:dC or O6-MeG:dT bound compared with the corresponding situations in structures of complexes of Sulfolobus solfataricus Dpo4, a bypass pol that favors C relative to T by a factor of ∼4, helps rationalize the more error-prone synthesis opposite the lesion by hpol η.
Real-time femtomolar detection of cancer biomarkers from photoconjugated antibody–phage constructs

Here we describe novel covalent conjugates of antibody–phage for the detection of multiple cancer biomarkers using real time immuno-polymerase chain reaction (immuno-PCR). While the conventional process of immuno-PCR utilizes DNA-conjugated antibodies, chemical modification of antibodies not only reduces antibody affinity but also creates a heterogeneous population of products. However, phage naturally encapsulate genomic DNA, which can be used as a PCR template. To produce covalently conjugated antibody–phage constructs without recombinant antibody expression or chemical modification of antibodies, we incorporated a photocrosslinkable non-canonical amino acid within an antibody-binding domain displayed on one of the phage coat proteins. To correlate antigen presence to a specific DNA sequence, the phage genomes were modified with domains that recognized specific sets of primers. The crosslinked antibody–phage conjugates were then tested in a sandwich-type immunoassay using real-time PCR where low pg ml−1 concentrations of antigen could be detected and identified from a single solution containing a mixture of three different types of cancer biomarkers.
Single- and Multi-Period Portfolio Optimization with Cone Constraints and Discrete Decisions

Portfolio optimization literature has come quite far in the decades since the first publication, and many modern models are formulated using second-order cone constraints and take discrete decisions into consideration. In this study we consider both single-period and multi-period portfolio optimization problems based on the Markowitz (1952) mean/variance framework, where there is a trade-off between expected return and the risk that the investor may be willing to take on. Our model is aggregated from current literature. In this model, we have included transaction costs, conditional value-at-risk (CVaR) constraints, diversification-by-sector constraints and buy-in-thresholds. Our numerical experiments are conducted on portfolios drawn from 20 to 400 different stocks available from the S&P 500 for the single period-model. The multi-period portfolio optimization model is obtained using a binary scenario tree that is constructed with monthly returns of the closing price of the stocks from the S&P 500. We solve these models with a MATLAB based Mixed Integer Linear and Nonlinear Optimizer (MILANO). We provide substantial improvement in runtimes using warmstarts in both branch-and-bound and outer approximation algorithms.
Seasonal Dynamics of Academic Achievement Inequality by Socioeconomic Status and Race/Ethnicity: Updating and Extending Past Research With New National Data

Early studies examining seasonal variation in academic achievement inequality generally concluded that socioeconomic test score gaps grew more over the summer than the school year, suggesting schoo...
Transferring State-of-the-Art Immutability Analyses: Experimentation Toolbox and Accuracy Benchmark

Immutability analysis is important to software testing, verification and validation (V&V) because it can be used to identify independently testable functions without side-effects. Existing tools for immutability analysis are largely academic prototypes that have not been rigorously tested for accuracy or have not been maintained and are unable to analyze programs written in later versions of Java. In this paper, we re-implement two prominent approaches to inferring the immutability of an object: one that leverages a points-to analysis and another that uses a type-system. In addition to supporting Java 8 source programs, our re-implementations support the analysis of compiled Java bytecode. In order to evaluate the relative accuracy, we create a benchmark that rigorously tests the accuracy boundaries of the respective approaches. We report results of experiments on analyzing the benchmark with the two approaches and compare their scalability to real world applications. Our results from the benchmark reveal that points-to based approach is more accurate than the type inference based approach in certain cases. However, experiments with real world applications show that the points-to based approach does not scale well to very large applications and a type inference based approach may offer a scalable alternative.
Dual functions of Discoidin domain receptor coordinate cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors

Integrated analyses of regulated effector genes, cellular processes, and extrinsic signals are required to understand how transcriptional networks coordinate fate specification and cell behavior during embryogenesis. Migratory pairs of cardiac progenitors in the tunicate Ciona provide the simplest model of collective migration in chordate embryos. Ciona cardiopharyngeal progenitors (aka trunk ventral cells, TVCs) polarize as leader and trailer cells, and migrate between the ventral epidermis and trunk endoderm, which influences collective polarity. Using functional perturbations and quantitative analyses, we show that the TVC-specific and collagen-binding Discoidin-domain receptor (Ddr) cooperates with Integrin-β1 to promote cell-matrix adhesion to the epidermis. We found that endoderm cells secrete a collagen, Col9-a1, that is deposited in the basal epidermal matrix and activates Ddr at the ventral membrane of migrating TVCs. A functional antagonism between Ddr/Intβ1-mediated cell-matrix adhesion and Vegfr signaling appears to modulate the position of cardiopharyngeal progenitors between the endoderm and epidermis. Finally, we show that Ddr activity promotes leader-trailer-polarized BMP-Smad signaling independently of its role in cell-matrix adhesion. We propose that dual functions of Ddr act downstream of cardiopharyngeal-specific transcriptional inputs to coordinate subcellular processes underlying collective polarity and directed migration.
Quantifying left atrial structure and function using single-plane tissue-tracking cardiac magnetic resonance.

Abstract Purpose Left atrial (LA) structure and function are important markers of adverse cardiovascular outcomes. Tissue-tracking cardiovascular magnetic resonance (CMR) accurately quantifies LA volume, strain, and strain rate based on biplane long-axis imaging. We aimed to assess the accuracy of the LA indices quantification from single-plane tissue-tracking CMR. Methods We included 388 subjects (mean age 57±13, male 70%) whose cine CMR images in sinus rhythm were available in both four-chamber and two-chamber views: 162 patients from the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) Study, 208 patients from atrial fibrillation cohort, and 18 healthy volunteers. The group was divided into the training set (n = 291) and the test set (n = 97). In the training set, we compared the LA indices derived from biplane imaging and single-plane imaging (a four-chamber view), and developed regression equations. In the test set, we used the regression equations to estimate the LA indices from the single-plane imaging, and quantified the accuracy of the estimation against the LA indices from the biplane. Results In the training set, all the LA indices from the single-plane imaging tended to be systematically underestimated compared with those from the biplane imaging, however, the correlation coefficient was high (r2 = 0.73–0.90, p Conclusions LA volumetric indices measured from single-plane tissue-tracking CMR are highly accurate and reproducible with reference to those derived from the standard biplane imaging. The reproducibility of LA strain and strain rate indices from single-plane tissue-tracking CMR is excellent but the variability is higher than that of the volumetric indices.
The importance of OH− transport through anion exchange membrane in microbial electrolysis cells

Abstract In two-chamber microbial electrolysis cells (MECs) with anion exchange membranes (AEMs), a phosphate buffer solution (PBS) is typically used to avoid increases in catholyte pH as Nernst equation calculations indicate that high pHs adversely impact electrochemical performance. However, ion transport between the chambers will also impact performance, which is a factor not included in those calculations. To separate the impacts of pH and ion transport on MEC performance, a high molecular weight polymer buffer (PoB), which was retained in the catholyte due to its low AEM transport and cationic charge, was compared to PBS in MECs and abiotic electrochemical half cells (EHCs). In MECs, catholyte pH control was less important than ion transport. MEC tests using the PoB catholyte, which had a higher buffer capacity and thus maintained a lower catholye pH (
Geology of Danielson Crater, Mars

The Danielson impact crater is located at 8°N 353°E, between Meridiani Planum and Arabia Terra regions. The impact crater hosts one of the best-preserved successions of layered deposits inside a Ma...
Complete genome sequence of Achromobacter spanius type strain DSM 23806T, a pathogen isolated from human blood.

Abstract Objectives Achromobacter spanius is a newly described, non-fermenting, Gram-negative, coccoid pathogen isolated from human blood. Whole-genome sequencing of the A. spanius type strain was performed to investigate the mechanism of pathogenesis of this strain at a genomic level. Methods The complete genome of A. spanius type strain DSM 23806T was sequenced using single-molecule real-time (SMRT) DNA sequencing. Results The complete genome of DSM 23806T consists of one circular DNA chromosome of 6 425 783 bp with a G + C content of 64.26%. The entire genome contains 5804 predicted coding sequences (CDS) and 55 tRNAs. Genomic island (GI) analysis showed that this strain encodes several important pathogenesis- and resistance-related genes. Conclusions These results strongly suggest that GIs provide some fitness advantages in A. spanius type strain DSM 23806T. This report provides an extensive understanding of A. spanius at a genomic level as well as an understanding of the evolution of A. spanius.
Characteristics of Normal Inner Experience

We have, for the past six chapters, examined the thinking of individuals, one at a time, and so have accomplished the major goal of this project, familiarizing ourselves with a sampling of the basic data of psychology: individual experience as it is lived by the persons themselves. We have also had a chance to exercise the supplemental goal of suspending our hypothesis generation until such time as we have acquired as much data as are available.
Dynamical Behavior of Solids

We now turn to the treatment of the dynamics of deformable solids. The basis of the discussion is very similar to that of statics in the previous chapter, as the time-dependence adds only one term to the equations relating stress and strain. The formalism we develop here will allow simple problems to be solved, developing an understanding that can be applied to more complex, but often more realistic, problems; these typically must be solved through numerical techniques.
Physical Space. Abstract Spaces

Whereas the Random House Dictionary of the English Languagee(6) lists as many as nineteen connotations of the word “space,” for the purposes of this exposition it is sufficient to consider only two, which we shall designate more specifically by the terms “physical” and “abstract” space.
Data Generated by New Technologies and the Law: A Guide for Massachusetts Practitioners

This brief paper, created as part of a training on new technologies and evidence for MCLE New England, outlines the standards used to compel disclosure of information under the Stored Communication Act, and reviews the types of data stored on various consumer devices and their likely custodians, as well as cases and notes relevant to each devices. The paper serves as a quick introduction and checklist for those considering gathering information from these devices in the course of investigations in Massachusetts. The devices outlined include cell phones, social media platforms, secure messaging services, fitness trackers, home assistant devices (or "smart speakers"), and in-home "Internet of Things" devices. The 2019 edition updates and expands on the prior edition, with an expanded discussion of facial analysis technology.
Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer.

Tumor progression locus 2 (Tpl2) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family of serine/threonine kinases. Deletion of the Tpl2 gene is associated with a significantly higher number of papillomas and cutaneous squamous cell carcinomas (cSCCs). Overexpression of hepatocyte growth factor (HGF) and its receptor MET is abundant in cSCC and can lead to increased proliferation, migration, invasion or resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. The aim of this study was to address whether the increased tumor burden in Tpl2 −/− mice is due to aberrant HGF/MET signaling. C57Bl/6 wild type (WT) and Tpl2 −/− mice were subjected to a two-stage chemical carcinogenesis protocol for one year. At the time of promotion half of the mice received 44 mg/kg capmatinib (INC 280), a pharmacological inihibitor of MET, in their diet. Tpl2−/− mice had signficantly higher tumor incidence and overall tumor burden compared to WT mice. Further, carcinogen-intiated Tpl2 −/− mice could bypass the need for promotion, as 89% of Tpl2 −/− mice given only DMBA developed papillomas. v-rasHa -transduced keratinocytes and SCCs from Tpl2 −/− mice revealed an upregulation in HGF and p-MET signaling compared to WT animals. Long-term capmatinib treatment had no adverse effects in mice and capmatinib-fed Tpl2 −/− mice had a 60% reduction in overall tumor burden. Further, no tumors from Tpl2 −/− mice fed capmatinib underwent malignant conversion. In summary targeting MET may be a potential new strategy to combat cutaneous squamous cell carcinomas that result from dysregulation in MAPK signaling.