cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4273: DNA methyltransferase 3B mediates 5-aza-deoxycytidine hypersensitivity in cisplatin-sensitive and cisplatin-resistant pluripotent embryonal carcinoma cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Testicular germ cell tumors (TGCTs) are the most common solid tumors of 15-35 year old men. TGCT patients are frequently cured with cytotoxic cisplatin-based therapy. However, TGCT patients refractory to cisplatin-based chemotherapy have a poor prognosis, as do those having a late relapse. Pluripotent embryonal carcinoma (EC) are the malignant counterparts to embryonic stem (ES) cells and are considered the stem cells of TGCTs. Here we show that human EC cells are highly sensitive to 5-aza-deoxycytidine (5-aza-CdR) as compared to a variety of somatic solid tumor cells. This is associated with markedly abundant expression of the pluripotency-associated DNA methyltransferase 3B, DNMT3B, as compared to somatic tumor cells. Knockdown of DNMT3B in EC cells resulted in substantial resistance to 5-aza-CdR, strongly implicating that 5-aza-CdR sensitivity is mechanistically linked to high levels of DNMT3B. Intriguingly, cisplatin resistant EC cells retain an exquisite sensitivity to low dose 5-aza-CdR treatment and pretreatment of 5-aza-CdR re-sensitizes these cells to cisplatin-mediated toxicity. These findings indicate that high expression of DNMT3B, a likely byproduct of their pluripotent and germ cell nature, sensitizes TGCT-derived EC cells to low dose 5-aza-CdR treatment. Decreased proliferation and survival with low nanomolar concentrations of 5-aza-CdR is associated with ATM activation, H2AX phosphorylation, increased expression of p21, and the induction of genes known to be methylated in TGCTs. Data pertaining to the mechanism of DNMT3B-dependent, 5-aza-CdR hypersensitivity in TGCTs will be presented. Efforts to extend this work to clinical samples are ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4273.
Design of Deep Web Semantic Search System

A semantic search system of Deep Web is designed and implemented based on the approach of ontology retrieval technology aim to Deep Web characteristics.Then,the new system can meet the users' need to obtain the high valued Deep Web information.
The Concept of Immune-based Therapies in Chronic Viral Infections

Treatment of recurrent herpes simplex virus (HSV) infection with a vaccine was attempted as early as 1938. The concept of immune therapy is based on the premise that vaccine administration may augment host immunity, resulting in better control of the infection. The guinea pig model is useful in the study of recurrent HSV infection for several reasons. This animal model mimics human infection, with self-limited primary vulvovaginitis developing after inoculation with HSV. Despite a full range of host immune responses, the virus persists in a latent state within sensory ganglia. Periodically, the latent virus reactivates to produce recurrent genital infections. Use of the guinea pig model has made it possible to demonstrate that the administration of HSV glycoprotein vaccines to infected animals results in a significant reduction in the frequency and severity of recurrences. Studies demonstrate that a variety of factors influence the effectiveness of immunotherapy. These factors include not only immunogen and dose but also the route of administration, timing of treatment relative to primary infection, and adjuvant formulation. Investigations of HSV immunotherapy in the guinea pig model provide the first controlled experimental data indicating that vaccine administration to an infected host can favorably alter the natural history of a persistent infection.
GP49, an invariant GPI-anchored antigen of Giardia lamblia.

Giardia lamblia is a primitive protozoan and a major cause of waterbome enteric disease throughout tropical and temperate zones. The ability to grow the infective trophozoites in culture as well as the discovery of the method of in vitro encystation made it possible to study the biology of this primitive protozoan and to characterize the surface antigens. Giardia trophozoites are exposed to high concentrations of fatty acids in the human small intestine. This raises the possibility that intestinal fatty acids may become incorporated into Giardia. Therefore, we determined the patternm of fatty acylationof Giardia surface molecules
The Time Value of Money

You may have heard the expression, “A dollar today is worth more than a dollar tomorrow,” which is because a dollar today has more time to accumulate interest. The time value of money deals with this basic idea more broadly, whereby an amount of money at the present time may be worth more than in the future because of its earning potential. To be self-contained for readers new to finance, the chapter covers: interest rate and return rate; simple interest and compound interest, including a nonintegral number of periods, continuous compounding, and varying interest rates; the net present value and internal return rate; simple ordinary annuities, perpetuities, amortization theory, and annuities with varying payments and interest; applications of annuities; and applications to stock and bond valuation.
Selectivity in Postencoding Connectivity with High-Level Visual Cortex Is Associated with Reward-Motivated Memory.

Reward motivation has been demonstrated to enhance declarative memory by facilitating systems level consolidation. While high reward information is often intermixed with lower reward information during an experience, memory for those experiences prioritizes high value information. How is this selectivity achieved? One possibility is that post-encoding consolidation processes bias memory strengthening to those representations associated with higher reward. To test this hypothesis, we investigated the influence of differential reward motivation on the selectivity of post-encoding markers of systems-level memory consolidation. Human participants encoded intermixed, trial-unique memoranda that were associated with either high or low value during fMRI acquisition. Encoding was interleaved with periods of rest, allowing us to investigate experience-dependent changes in connectivity as they related to later memory. Behaviorally, we found that reward motivation enhanced 24-hour associative memory. Analysis of patterns of post-encoding connectivity showed that even though learning trials were intermixed, there was significantly greater connectivity with regions of high-level, category-selective visual cortex associated with high reward trials. Specifically, increased connectivity of category-selective visual cortex with both the ventral tegmental area and the anterior hippocampus predicted associative memory for high- but not low-reward memories. Critically, these results were independent of encoding-related connectivity and univariate activity measures. Thus, these findings support a model by which the selective stabilization of memories for salient events is supported by post-encoding interactions with sensory cortex associated with reward. SIGNIFICANCE STATEMENT Reward motivation is thought to promote memory by supporting memory consolidation. Yet, little is known as to how brain selects relevant information for subsequent consolidation based on reward. We show that experience-dependent changes in connectivity of both the anterior hippocampus and the ventral tegmental area with high-level visual cortex selectively predicts memory for high-reward memoranda at a 24-hour delay. These findings provide evidence for a novel mechanism guiding the consolidation of memories for valuable events, namely post-encoding interactions between neural systems supporting mesolimbic dopamine activation, episodic memory, and perception.
Sex-biased oviposition by a nursery pollinator on a gynodioecious host plant: Implications for breeding system evolution and evolution of mutualism

Dioecy, a breeding system where individual plants are exclusively male or female, has evolved repeatedly. Extensive theory describes when dioecy should arise from hermaphroditism, frequently through gynodioecy, where females and hermaphrodites coexist, and when gynodioecy should be stable. Both pollinators and herbivores often prefer the pollen-bearing sex, with sex-specific fitness effects that can affect breeding system evolution. Nursery pollination, where adult insects pollinate flowers but their larvae feed on plant reproductive tissues, is a model for understanding mutualism evolution but could also yield insights into plant breeding system evolution. We studied a recently established nursery pollination interaction between native Hadena ectypa moths and introduced gynodioecious Silene vulgaris plants in North America to assess whether oviposition was biased toward females or hermaphrodites, which traits were associated with oviposition, and the effect of oviposition on host plant fitness. Oviposition was hermaphrodite-biased and associated with deeper flowers and more stems. Sexual dimorphism in flower depth, a trait also associated with oviposition on the native host plant (Silene stellata), explained the hermaphrodite bias. Egg-receiving plants experienced more fruit predation than plants that received no eggs, but relatively few fruits were lost, and egg receipt did not significantly alter total fruit production at the plant level. Oviposition did not enhance pollination; egg-receiving flowers usually failed to expand and produce seeds. Together, our results suggest that H. ectypa oviposition does not exert a large fitness cost on host plants, sex-biased interactions can emerge from preferences developed on a hermaphroditic host species, and new nursery pollination interactions can arise as negative or neutral rather than as mutualistic for the plant.
Approach to equilibrium of a quantum system and generalization of the Montroll–Shuler equation for vibrational relaxation of a molecular oscillator

The approach to equilibrium of a quantum mechanical system in interaction with a bath is studied from a practical as well as a conceptual point of view. Explicit memory functions are derived for given models of bath couplings. If the system is a harmonic oscillator representing a molecule in interaction with a reservoir, the generalized master equation derived becomes an extension into the coherent domain of the well-known Montroll–Shuler equation for vibrational relaxation and unimolecular dissociation. A generalization of the Bethe–Teller result regarding energy relaxation is found for short times. The theory has obvious applications to relaxation dynamics at ultra-short times as in observations on the femtosecond time scale and to the investigation of quantum coherence at those short times. While vibrational relaxation in chemical physics is a primary target of the study, another system of interest in condensed matter physics, an electron or hole in a lattice subjected to a strong DC electric field that gives rise to well-known Wannier–Stark ladders, is naturally addressed with the theory. Specific system–bath interactions are explored to obtain explicit details of the dynamics. General phenomenological descriptions of the reservoir are considered rather than specific microscopic realizations.
Level of Fimbriation Alters the Adhesion of Escherichia coli Bacteria to Interfaces

Adhesion of bacteria to interfaces is the first step in pathogenic infection, in biofilm formation, and in bioremediation of oil spills and other pollutants. Bacteria use a variety of surface structures to promote interfacial adhesion, with the level of expression of these structures varying in response to local conditions and environmental signals. Here, we investigated how overexpression of type 1 fimbriae, one such appendage, modifies the ability of Escherichia coli to adhere to solid substrates, via biofilm formation and yeast agglomeration, and to oil/water interfaces, via a microbial adhesion to hydrocarbon assay. A plasmid that enables inducible expression of E. coli MG1655 type 1 fimbriae was transformed into fimbriae-deficient mutant strain MG1655ΔfimA. The level of fimH gene expression in the engineered strain, measured using quantitative real-time PCR, could be tuned by changing the concentration of inducer isopropyl β-d-1-thiogalactopyranoside (IPTG), and was higher than that in strain MG1655....
Measurements of the absorption of lysozyme-water and alanine in the 10-60 cm-1 range using infrared synchrotron radiation

Absorption measurements of powders of lysozyme-water and crystals of L-alanine have been performed in the 10 to 60 cm -1 spectral region at the National Synchrotron Light Source at Brookhaven National Laboratory.
Testing the cognitive catalyst model of rumination with explicit and implicit cognitive content.

Abstract Background and objectives The cognitive catalyst model posits that rumination and negative cognitive content, such as negative schema, interact to predict depressive affect. Past research has found support for this model using explicit measures of negative cognitive content such as self-report measures of trait self-esteem and dysfunctional attitudes. The present study tested whether these findings would extend to implicit measures of negative cognitive content such as implicit self-esteem, and whether effects would depend on initial mood state and history of depression. Method Sixty-one undergraduate students selected on the basis of depression history (27 previously depressed; 34 never depressed) completed explicit and implicit measures of negative cognitive content prior to random assignment to a rumination induction followed by a distraction induction or vice versa. Dysphoric affect was measured both before and after these inductions. Results Analyses revealed that explicit measures, but not implicit measures, interacted with rumination to predict change in dysphoric affect, and these interactions were further moderated by baseline levels of dysphoria. Limitations Limitations include the small nonclinical sample and use of a self-report measure of depression history. Conclusions These findings suggest that rumination amplifies the association between explicit negative cognitive content and depressive affect primarily among people who are already experiencing sad mood.
The Need for Improved Access to Mental Health Services for Youth With Medically Unexplained Symptoms.

Medically unexplained symptoms (MUS) are common in children and adolescents, and recent efforts have been made to better understand their clinical correlates and to improve assessment and treatment...
Elastic coupling power stroke mechanism of the F1-ATPase molecular motor.

The angular velocity profile of the 120° F 1 -ATPase power stroke was resolved as a function of temperature from 16.3 to 44.6 °C using a Δμ ATP = −31.25 k B T at a time resolution of 10 μs. Angular velocities during the first 60° of the power stroke (phase 1) varied inversely with temperature, resulting in negative activation energies with a parabolic dependence. This is direct evidence that phase 1 rotation derives from elastic energy (spring constant, κ = 50 k B T ·rad −2 ). Phase 2 of the power stroke had an enthalpic component indicating that additional energy input occurred to enable the γ-subunit to overcome energy stored by the spring after rotating beyond its 34° equilibrium position. The correlation between the probability distribution of ATP binding to the empty catalytic site and the negative E a values of the power stroke during phase 1 suggests that this additional energy is derived from the binding of ATP to the empty catalytic site. A second torsion spring (κ = 150 k B T ·rad −2 ; equilibrium position, 90°) was also evident that mitigated the enthalpic cost of phase 2 rotation. The maximum Δ G ǂ was 22.6 k B T , and maximum efficiency was 72%. An elastic coupling mechanism is proposed that uses the coiled-coil domain of the γ-subunit rotor as a torsion spring during phase 1, and then as a crankshaft driven by ATP-binding–dependent conformational changes during phase 2 to drive the power stroke.
Legal Learning for Life: Legal Immersion Fluency Education (LIFE)

The concept of “thinking like a lawyer,” the focus of traditional law school study, takes too narrow a view of how lawyers practice and the range and reach of legal work. Although critical legal thinking is important, it is merely one component of effective lawyering. In addition to learning how to “think like a lawyer,” law school is the place where students learn the language of the law. The author states that law schools should take advantage of the best known and most effective approach to learning a new language — the immersion method — and that the primary characteristic of the immersion method is teaching language and culture in contextualized combination. By creating an engaging learning environment where law students become fluent in the language and practice of effective and compassionate problem solving, the health and well-being of individual lawyers and the legal profession will improve.
The Transition Journey: Time to Systematically Address Transition Planning to Adult Health Care

* Abbreviation: YSHCN — : youth with special health care needs Since the 1970s, researchers and clinicians have documented the difficulties and subsequent poor health outcomes experienced by youth with special health care needs (YSHCN) during the transition from pediatric to adult health care. In 2002, Pediatrics published the American Academy of Pediatrics recommendation of improving the transition of care for YSHCN from pediatric- to adult-focused care1 as a step toward meeting the goals of Healthy People 2010 . The recommendations specified that all YSHCN have appropriate transition and transfer planning through education and generation of a transfer summary. The goal was to ensure “high-quality, developmentally appropriate health care services are available in an uninterrupted manner as the person moves from adolescence” to “maximize lifelong functioning and well-being for all youth”2 regardless of whether the individual has a special health care need. Sixteen years later, in this issue of Pediatrics , Lebrun-Harris et al3 visit the follow-up question: What is the current state of health care transition planning in the United States? Perhaps, after over 40 years of discussing improvements in transition, … Address correspondence to Megumi J. Okumura, MD, MAS, Division of General Pediatrics, University of California, San Francisco, 3333 California St STE 245, San Francisco, CA 94118. E-mail: megumi.okumura{at}ucsf.edu
The syntax of Basque allocutive clitics

A key piece of evidence in favor of recent proposals that speech act roles are encoded in the syntax comes from languages with “allocutivity” –agreement with non-thematic addressees. This paper analyzes the syntax of allocutive morphemes in the best studied allocutive language, Basque. It is shown that properties of these morphemes, including morpheme order and the way allocutive morphemes condition exponence of neighboring heads can be modeled using standard assumptions about cliticization, head-adjunction and case in Basque. The analysis lends support to a central idea in recent literature on the syntax of speech act roles, namely that addressees are encoded by a nominal element introduced in the left periphery. This paper proposes that, in Basque, this nominal element is overt, with a distribution that obeys principles similar to those for thematic addressees.
Acute Stroke Therapy in Infective Endocarditis – Case Series and Systematic Review (P6.295)

Objective: To report our clinical experience managing acute ischemic stroke secondary to infective endocarditis. Background: Acute ischemic stroke (AIS) is common in patients with infective endocarditis (IE). Use of IV thrombolytic therapy (IV-tPA) has been reported and appears to carry greater risk of hemorrhage, while reports of endovascular therapy are rare. Design/Methods: A retrospective review was done of 116 consecutive patients with IE who were seen by stroke neurology in a tertiary care center from January 2015 to July 2016. One case using IV-tPA and one case using endovascular thrombectomy. We searched PubMed from inception to August 2016 and systematic review was performed to evaluate acute stroke therapy in IE. Results: In case 1, an 82 year old female with prosthetic aortic valve endocarditis and atrial fibrillation presented with slurred speech and right hemiplegia. IV-tPA was given within 2.5 hours, and NIHSS improved from 11 to 1 over 24 hours. CT Brain done 24 hours post-tPA revealed a small L thalamic hemorrhage. In case 2, a 49 year old IV drug-using male with prior IE and current prosthetic aortic valve endocarditis developed right middle cerebral artery (MCA) occlusion with an NIHSS 17. Endovascular thrombectomy was performed with successful TICI 3 recanalization. CT Brain done 24 hours post-thrombectomy showed evolving right MCA infarct with hemorrhagic conversion. Systematic review revealed 7 reports of IV thrombolysis, 5 reports of mechanical thrombectomy, and 3 reports with intra-arterial thrombolysis plus endovascular thrombectomy. Including our cases, IV thrombolysis, alone, had a hemorrhagic complication rate of 82%. Endovascular thrombectomy alone, with at least TICI IIb recanalization, had a hemorrhagic complication rate of 17%. Intra-arterial thrombolysis and endovascular thrombectomy together had a hemorrhagic complication rate of 0%. Conclusions: Endovascular thrombectomy alone appears to be safer than IV-tPA alone in the management of AIS in patients with IE. Disclosure: Dr. Marquardt has nothing to disclose. Dr. Cho has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Uchino has nothing to disclose. Dr. Wisco has nothing to disclose.
Chromatin Modifications in Toxicology.

Histone modifications regulate chromatin structure and function. Primary and secondary metabolites stemming from environmental and chemical exposures may play a critical role in the underlying epigenomic state of a cell through covalent histone modifications. Future investigations should be focused on characterizing the “Histone Code” when performing toxicogenomic analyses.
Global Leadership: A Transnational Perspective

The clash of cultures, coupled with rapid technological advances, seems to be pushing us in paradoxical directions. On the one hand, the world seems to be falling apart; while on the other, the world seems to be converging. Do we have thoughtful leaders to guide us through these uncertain times? As globalization breaks down barriers, global leaders are becoming more visible players on the world stage. From executives of multinational corporations (e.g., high-tech entrepreneurs in Silicon Valley) to social activists (e.g., Malala Yousafzai), individuals from many different cultural backgrounds and ages are reshaping the way we see global leadership. These global leaders have to contend with a variety of transnational contexts that call for different leadership styles. This book assesses four of these styles – transactional, participatory, transformational, and directive – with representative case studies for each. It provides practical skills that global leaders must master in order to be more effective at the transnational level – cultivating a global mindset; developing intercultural communication; leveraging diversity and inclusion; and managing intercultural conflict. Global Leadership is valuable reading for educators in undergraduate and graduate leadership programs; practitioners involved in global for-profit and nonprofit organizations; and leadership educators interested in exploring the impact of technology on global leadership. It provides an excellent balance between the study and practice of global leadership.
Poor awareness of IADL deficits is associated with reduced regional brain volume in older adults with cognitive impairment.

Abstract Performance of instrumental activities of daily living (IADLs) can become compromised in older adults with mild cognitive impairment (MCI). Patients’ level of insight into their everyday functioning varies both amongst individuals and across domains assessed, with some individuals exhibiting complete unawareness of deficits. The current cross-sectional study examined the neuroanatomical substrates of self-awareness in order to help explain the variability in this phenomenon in older adults across a continuum of cognitive impairment. Eighty-five participants (ages 54–88, mean age = 73 years, 57% female, 89% Caucasian) diagnosed with MCI or mild probable dementia underwent structural magnetic resonance imaging. Level of self-awareness was assessed by calculating the discrepancy between objective and subjective performance across six IADLs (Financial Management, Driving, Grocery Shopping, Nutrition Evaluation, Medication Management, and Telephone Use). Over-estimation of current abilities occurred in 13–31% of the sample depending on which IADL was evaluated. Poor awareness was significantly related to reduced volume in the bilateral medial prefrontal cortex, middle and posterior cingulate cortex, right insular cortex, and cerebellum. No associations were found with total white matter lesion load. These findings were broadly consistent across all functional domains assessed, supporting the theory that cortical midline and cerebellar structures are involved in self-referential processing across a variety of different cognitive and behavioral skills. Longitudinal studies are needed to confirm this association.
Dunn-Hensley, Anna of Denmark and Henrietta Maria: Virgins, Witches, and Catholic Queens (Palgrave Macmillan, 2017)

Review of Susan Dunn-Hensley, Anna of Denmark and Henrietta Maria: Virgins, Witches, and Catholic Queens (New York: Palgrave Macmillan, 2017).
Quantifying risk and accuracy in cancer risk assessment: the process and its role in risk management problem-solving.

A better understanding of chemical-induced cancer has led to appreciation of similarities to problems addressed by risk management of radiation-induced toxicity. Techniques developed for cancer risk assessment of toxic substances can be generalized to toxic agents. A recent problem-solving approach for risk management of toxic substances developed for the U.S. Department of Health and Human Services, and the role of risk assessment and how uncertainty should be treated within the context of this approach, is discussed. Finally, two different methods, research into the assumptions underlying risk assessment and the modification of risk assessment/risk management documents, are used to illustrate how the technique can be applied.
CHARACTERIZATION OF NATURAL KILLER CELL HEMATOPOIETIC PRECURSORS IN HUMAN HEMATOPOIESIS

Natural Killer (NK) cells have been characterized as cytotoxic lymphocytes that are key in regulating viral infections and combatting cancer. In contrast to B and T cells, there has not been a detailed examination of the developmental trajectory of human NK cells. Conflicting reports in literature state that NK cells can develop from both lymphoid and myeloid cell progenitors. Here, we utilized mass cytometry (CyTOF) to perform a multiplexed analysis of NK cell development on healthy human bone marrow. To address the current gap in knowledge, we built a comprehensive CyTOF panel to include lymphoid markers, myeloid markers, and various regulatory factors shown to be important both in mouse and human NK cell development across 4 donor samples. We analyzed this data with multiple supervised and unsupervised single cell trajectory algorithms in order to model NK developmental processes. This approach allows for unbiased observations across developmental lineages and the reconciliation of the conflicting literature. The ability to simultaneously measure multiple cellular features, including phenotypic proteins, transcription factors, and regulatory enzymes allowed us to identify a novel potential NK lineage-restricted progenitor in adult human bone marrow. We have found potential CD34+ NK progenitors with different combinations of surface markers previously used to identify NK progenitors and regulatory markers such as IRF8, NFIL3, ID2 and TdT. Our findings here show that NK cells may be generated through two distinct fate pathways. Our next step is to analyze the capacity of this novel progenitor subpopulation to generate mature and functional CD56+ NK cells in vitro, through co culture with the OP9 and OP9-DL4 cell lines. Ultimately, our studies will shed light on the knowledge of early stages of NK lineage commitment.
Temperature profile and double images in the inferior mirage

Desert mirages were simulated in the laboratory by heating a flat surface of sand. This showed that a boundary layer of air, of only a few millimeters immediately covering a heated surface has nearly the same thickness over a wide range of temperatures. It consists of a region producing an inverted image, and another producing an erect image depending on the relative distances between observer, heated surface and object. Measurement of distances and heights show angles of incidence greater than angles of reflection. Air refractive index measurements agree with involvement of the critical angle in ray bending. An analogy with density gradient sucrose solutions also shows double images, inverted and erect. It is assumed that a similar situation exists outdoors. Specular reflection over rough surfaces can be described as a mirage, but it is seen at a wider range of viewing angles, and it does not require a temperature gradient. It is always present, but it can be obliterated by a higher intensity of diffuse reflection.
Development and Validation of a Sensitive and Specific LC‐MS/MS Cocktail Assay for CYP450 Enzymes; Application to Study the Effect of Catechin on Rat Hepatic CYP Activity

A sensitive and specific liquid chromatography tandem mass spectrometric (LC-MS/MS) method that enables the simultaneous quantification of probe substrates and metabolites of cytochrome P450 (CYP) enzymes was developed and validated. These substrates (metabolites)-coumarin (7-hydroxycoumarin), tolbutamide (4-hydroxytolbutamide), S-mephenytoin (4-hydroxymephenytoin), dextromethorphan (dextrorphan), and testosterone (6β-hydroxytestosterone)-were utilized as markers for the activities of the major human CYP enzymes CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. Analytes were separated on Kinetex C18 column (2.1 × 50 mm, 5 μm) using a binary gradient mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Metabolites were detected and quantified by MS using multiple reaction monitoring at m/z 163 → 107.2 for 7-hydroxycoumarin, m/z 235 → 150.1 for 4-hydroxymephenytoin, m/z 287 → 171 for 4-hydroxytolbutamide, m/z 258 → 157.1 for dextrorphan, m/z 305 → 269 for 6β-hydroxytestosterone, and m/z 237 → 194 for the internal standard. The assay exhibited good linearity over a range of 10-500 ng/mL with acceptable accuracy and precision criteria. As a proof of concept, the developed cocktail assay was successfully used to examine the potential impact of catechin on the activity of the major rat liver CYP enzymes.
Costa Rica’s Water Paradox: Linking Rainforests and Droughts through the Water-Energy-Food-Environment Nexus in Guanacaste Province

Costa Rica is known as a verdant, tropical paradise with rich rainforests, abundant wildlife, striking mountains and volcanoes, and picturesque beaches. However, the perceived abundance of Costa Rica’s water resources is only true for part of the country. The same geography and climate that bring abundant precipitation to most of southern Costa Rica and its Caribbean coast also leave the northern Pacific province of Guanacaste with substantially less rainfall and even periods of severe drought. This case study focuses on Guanacaste province, which is a major tourist destination as well as one of the country’s most productive agricultural regions. Water from the lush Caribbean slopes of the Lake Arenal region is transported across the continental divide through extensive infrastructure projects. Passing through the semi-arid regions of Guanacaste, hydroelectric power generation, extensive irrigated agriculture, and tourism development use most of the water, supporting a rapidly growing regional economy but leaving increasingly less water for environmental flows. This case study introduces students to “nexus thinking” to explore the multiple and overlapping water, energy, and food (WEF) demands and ecological challenges present in Guanacaste province. Each sector and its interconnections with other sectors are examined in turn through introductory lectures, and enriched by WEF systems thinking activities and class discussions. At the conclusion of this case study curriculum, students will be able to identify and characterize points of intersection, i.e., the nexus, of WEF supply and demand, and trade-offs that exist between WEF resources and biodiversity conservation.
THE IMPACT OF THE REVISED UNITED NETWORK OF ORGAN SHARING (UNOS) HEART ALLOCATION POLICY ON TRANSPLANT WAITLIST TIMES AND POST TRANSPLANT MORTALITY

The recent change in the UNOS heart allocation policy was intended to prioritize heart transplantation (HT) for the sickest patients, and thus sought to prioritize severity of illness by dividing the heterogeneous population encompassed in the prior status 1A category to the more discrete status 1-3
Mental health of undocumented college students during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has caused a surge in mental health problems across the United States, and some reports suggest a more severe impact for racial and ethnic minorities. The present study was conducted to gain a preliminary understanding of the mental health consequences of the COVID-19 pandemic specifically for dreamers, i.e., undocumented immigrants who entered the U.S. as minors. A population of about 150 dreamers currently enrolled at a public university in Delaware were invited to participate in an online survey. The survey contained questions about demographics, mental health, academics, immigration, COVID-19 infection, and unemployment, in addition to mental health screens for anxiety (GAD-7), depression (PHQ-9), and stress (PSS-10). In total, 109 dreamers completed the survey. We observed remarkably high clinical levels of anxiety and depression: 47% of the dreamers met the clinical cutoff for anxiety, 63% met the cutoff for depression, and 67% (2 in 3) met the cutoff for anxiety and/or depression. Rates of anxiety and depression in our sample were significantly higher than those recently reported for college students overall, suggesting that dreamers may be experiencing a more severe mental health impact of the COVID-19 pandemic. We also found that pandemic-induced concerns about finances, COVID-19 infection, immigration, and unemployment (among other factors) were associated with greater anxiety, stress, and depression among the dreamers in our sample. The present findings are consistent with recent predictions by social scientists that the COVID-19 pandemic would have a disproportionately negative impact on the mental health of undocumented immigrants.
Geometry of Multiprimary Display Colors I: Gamut and Color Control

Displays that render colors using combinations of more than three lights are referred to as multiprimary displays. For multiprimary displays, the gamut, i.e., the range of colors that can be rendered using additive combinations of an arbitrary number of light sources (primaries) with modulated intensities, is known to be a zonotope, which is a specific type of convex polytope. We develop a complete, cohesive, and directly usable mathematical characterization of the geometry of the multiprimary gamut zonotope. Our characterization immediately identifies the surface facets, edges, and vertices and provides a parallelepiped tiling of the gamut. We relate the parallelepiped tilings of the gamut, that arise naturally in our characterization, to the flexibility in color control afforded by displays with more than four primaries, a relation that is further analyzed and completed in a Part II companion paper. We demonstrate several applications of the geometric representations we develop and highlight how the paper advances theory required for multiprimary display modeling, design, and color management and provides an integrated view of past work on on these topics. Additionally, by demonstrating that the mathematical results we develop and present also apply more broadly to a large class of three dimensional zonotopes, we highlight how our work on gamut representations connects with and furthers the study of zonotopes in geometry.
Factors Associated with Assisted Living Facility Closure.

BACKGROUND AND OBJECTIVES Assisted living facilities (ALFs) have experienced rapid growth in the past few decades. The expansion in the number of ALFs may cause markets to become oversaturated, and a greater risk of unprofitable ALFs to close. However, no studies have investigated ALF closure. This study adapted a model developed for the nursing home market for the ALF market to examine the organizational, internal, and external factors associated with closure. RESEARCH DESIGN AND METHODS Data on 1,939 ALFs operating in 2013 from Florida were used to estimate a logistic regression to examine the organizational, internal, and external factors that were associated with closure between 2013 and 2015. RESULTS During the two-year study period, 141 ALFs (7.3%) closed. Significant factors associated with increased odds of closure included fewer beds, not accepting Medicaid, and more deficiencies. Two factors (market concentration and population density) were marginally significant. DISCUSSION AND IMPLICATIONS The results of this study confirm the usefulness of a model that includes organizational, internal, and external factors to predict ALF closure. These outcomes highlight the concerns that closure can affect access to community based long-term care, especially for rural older adults, and indicate an expansion of Medicaid acceptance in ALFs could be protective against closure.
An Atheistic Argument from Ugliness

The theistic argument from beauty has what we call an ‘evil twin’, the argument from ugliness. The argument yields either what we call ‘atheist win’, or, when faced with aesthetic theodicies, ‘agnostic tie’ with the argument from beauty.
Stratospheric ozone and temperature responses to short-term solar ultraviolet variations - Reproducibility of low-latitude response measurements

Two independent 22-month time intervals of NIMBUS 7 solar backscattered UV (SBUV) ozone and stratospheric and mesospheric sounder (SAMS) temperature measurements for the upper stratosphere at low latitudes are analyzed to calculate mean responses to observed changes in solar ultraviolet spectral irradiance occurring on the time scale of the solar rotation period. Average cross-correlation functions of both SBUV ozone and SAMS temperature versus the solar 205 nm flux are in substantial agreement for these two intervals. Linear regression methods are applied to estimate response amplitudes or sensitivities. The derived sensitivities and phase lags relative to the 205 nm flux are also in approximate agreement for the two separate intervals although the temperature response measurements exhibit larger deviations. These results support the validity of previously reported measurements on the 27-day time scale, and impose firmer constraints on proposed theoretical models for the response of the stratosphere to solar UV forcing on both short and long time scales.
Corporate Social Responsibility and Workers’ Rights

Corporate Social Responsibility (CSR) brings an important dimension to the global economy. CSR can enhance human rights, labor rights, and labor standards in the workplace by joining consumer power and socially responsible business leadership—not just leadership in Nike headquarters in Oregon or Levi Strauss headquarters in California, but leadership in trading house headquarters in Taiwan and Hong Kong, and leadership at the factory level in Dongguan and Shenzhen. Ten years ago, I would not have said this. I viewed corporate social responsibility and corporate codes of conduct as public relations maneuvers to pacify concerned consumers. Behind a facade of social responsibility, profits always trumped social concerns. CSR was only a fig leaf hiding abusive treatment of workers. But in recent years some concrete, positive results from effectively applied CSR programs convinced me of their value. In Mexico in 2001, workers at the Korean- owned KukDong sportswear factory succeeded in replacing a management and government dominated trade union with a democratic union of the workers' choice. Compliance officials from Nike and Reebok, two of the largest buyers, joined forces with the Fair Labor Association (FLA) and the Workers Rights Consortium (WRC) enforcing their codes of conduct to achieve this result.
Binding of metabolically activated benzo(a)pyrene to nuclear macromolecules.

Summary The binding of metabolically activated [ 3 H]benzo( a )pyrene ([ 3 H]BP) to the DNA, RNA, histones, and nonhistones of isolated rat liver and lung nuclei was studied. Conditions for optimal binding to the nuclear components were determined. Upon incubation with isolated liver nuclei and reduced nicotinamide adenine dinucleotide phosphate, [ 3 H]BP was able to bind to nuclear components. The binding appeared to be covalent in nature. Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also increased the level of carcinogen binding. The addition of rat liver microsomes to the incubation systems greatly enhanced the level of [ 3 H]BP binding to the macromolecules in the nuclei from both the control and 3-methylcholanthrene-treated rats, and the maximal levels of binding obtained with these two types of nuclei were similar. The binding was inhibited by 7,8-benzoflavone or glutathione. Lung nuclei from control rats had very low AHH activity and did not exhibit appreciable carcinogen binding, whereas those from 3-methylcholanthrene-pretreated animals had slightly higher AHH activity and caused low levels of binding. The binding of [ 3 H]BP to lung nuclei was greatly enhanced by liver microsomes but only slightly by lung microsomes, which had rather low AHH activity. Several lines of evidence indicate that, in the control experiments (no reduced nicotinamide adenine dinucleotide phosphate added), the radioactivity associated with the macromolecule fractions is probably a background value rather than due to the binding caused by a specific interaction between benzo( a )pyrene and cytochrome P-450. The present study clearly demonstrates that a carcinogen activated at the microsomes can enter into the nucleus and react with its macromolecules; the carcinogen can also be activated by the monoxygenase system of the nuclear envelope. It appears that both the endoplasmic reticulum and the nuclear envelope are potentially important sites of carcinogen activation.
Numerical solutions to a kinetic model for sheath and presheath with charge exchange collisions of ions

Summary form only given. A kinetic model of the sheath and presheath is presented that includes the effects of charge-exchange collisions on the ions. The collisions are modeled as a sink for accelerated ions and as a source of cold ions. Solutions are obtained by numerical integration of Poisson's equation from a point near the plasma midplane to the wall. As the mean free path is decreased, the current density at the wall decreases and the potential profile in the presheath shows a smooth transition from a parabolic profile to a nearly cubic profile determined by the ion mobility. An approximate expression is found for the ion flux to the wall in the collisional limit.
Effective thermal conductivity of fully and partially saturated metal wicks

The purpose of the study is threefold: (1) to perform accurate experiments covering a wide range of porosities to determine the effective thermal conductivity of sintered fiber porous metals fully saturated with air, water, and water vapor; (2) to propose correlations for these cases, and to compare these correlations with existing analytical predictions, experimental correlations and data; and (3) to determine the effective thermal conductivity of porous metals partially saturated with water and water vapor, respectively. The experimental apparatus, based on the steady-state method of comparison, is designed and used for determining the effective thermal conductivity. The wicks are made of nickel 200, stainless steel 430, and copper, covering a porosity range 0.30-0.67. Based on the experimental results, a single correlation is derived for predicting the effective thermal conductivity of all wicks fully saturated with air, water, and water vapor. For two partially saturated wick specimens with both high porosity and large matrix thermal conductivity, a liquid-vapor transition zone is observed between the phases, which increases the total combined effective thermal conductivity of the specimen.
Genetic and Physiological Control of Serine and Glycine Biosynthesis in Saccharomyces

Abstract Two of the three known metabolic pathways to serine and glycine have been shown to be present in prototrophic yeast strains, i.e., the phosphorylated pathway from glycolytic intermediates and the glyoxylate pathway from tricarboxylic acid cycle intermediates. Two serine-glycine auxotrophs (ser1 and ser2) were found to be blocked in the phosphoglycerate pathway. The ser1 gene controls l-glutamate:phosphohydroxypyruvate transaminase biosynthesis, and the ser2 gene controls phosphoserine phosphatase biosynthesis. The other pathway to glycine, from isocitrate, is repressed by growth in glucose media, specifically, at isocitrate lyase and at the alanine:glyoxylate transaminase. This pathway is derepressed by growth to stationary phase in glucose media yielding high activity of these enzymes. The phosphorylated pathway appears to be the principal biosynthetic pathway to serine and glycine during growth on sugar media. Strains which are serine-glycine dependent in glucose media became capable of serine-glycine independent growth on acetate media. These results describe a method of physiological control of a secondary metabolic pathway allowing a single lesion in the principal biosynthetic pathway to produce auxotrophy. This may be termed conditional auxotrophy.
Improving virtual appliance management through virtual layered file systems

Managing many computers is difficult. Recent virtualization trends exacerbate this problem by making it easy to create and deploy multiple virtual appliances per physical machine, each of which can be configured with different applications and utilities. This results in a huge scaling problem for large organizations as management overhead grows linearly with the number of appliances. To address this problem, we introduce Strata, a system that combines unioning file system and package management semantics to enable more efficient creation, provisioning and management of virtual appliances. Unlike traditional systems that depend on monolithic file systems, Strata uses a collection of individual sotware layers that are composed together into the Virtual Layered File System (VLFS) to provide the traditional file system view. Individual layers are maintained in a central repository and shared across all file systems that use them. Layer changes and upgrades only need to be done once in the repository and are then automatically propagated to all virtual appliances, resulting in management overhead independent of the number of appliances. Our Strata Linux prototype requires only a single loadable kernel module providing the VLFS support and doesn't require any application or source code level kernel modifications. Using this prototype, we demonstrate how Strata enables fast system provisioning, simplifies system maintenance and upgrades, speeds system recovery from security exploits, and incurs only modest performance overhead.
Counter-rotating vortex patches in shear: a model of the effect of wind shear on aircraft trailing vortices

The shape and stability of twodimensional, uniform patches of vorticity in incompressible inviscid fluid are calculated. The object of the study is to investigate the effect of wind shear on traili...