cssi/SciSciGPT-SciSciNet huggingface dataset:
Marine algal toxins: Biochemistry, genetics, and molecular biology

Toxic compounds are frequently, but not universally, associated with alg,al blooms. Several dinoflagellate and diatom species are capable of toxin synthesis. Some bacteria are also capable of synthesizing at least one family of “algal” toxins. Previous work on algal toxins can be broadly grouped in four categories: observations on the variability in toxin production by single species or among strains of a species, frequently as a function of environmental growth conditions; isotope feeding studies to reveal the identity of the substrates that are precursors to the toxin compounds; the genetics of toxin production; and the pharmacological aspects of toxins. Information gleaned from these studies provides a firm foundation for launching more contemporaneous research efforts to understand the biochemistry and molecular biology of toxins. The goals are to develop an understanding of the machinery (i.e. the enzymes and the genes that encode them) required to synthesize toxins, to understand how this machinery is regulated by environmental conditions, and gain insights as to how the tox n biosynthetic genes evolved and(or) have been spread through the marine community. The production of toxic compounds is a common, but not universal, characteristic of harmful algal blooms (HABs). Surprisingly, only a few HAB toxins have been characterized and these are synthesized by only a limited number of algal species (Steidinger 1993). Toxigenic algae may, however, exert an inordinately large adverse impact on other members of the community because toxins can flow through aquatic food chains in a manner analogous to the movement of carbon or energy (Smayda 1992). Toxigenic algae thus may have significant impacts on ecosystem processes as toxins affect viability, growth, fecundity, and recruitment of a wide range of organisms. This manuscript is concerned with the biochemistry and genetics of toxin production by HAB species. Most information is for marine toxins as these have been better documented than the freshwater toxins. Saxitoxins, the causative agent of paralytic shellfish poisoning, are used as a model throughout this review as they are the best characterized marine toxin in terms of biochemistry and genetics. The physiology and ecology of the organisms that synthesize saxitoxins are also better documented than for other HAB species; this information permits a more robust interpretation of biochemical and genetic data for the saxitoxins than for other HAB toxins. Inauspiciously, very little is known about the molecular biology of HAB toxins, making this topic difficult to review. The goal in writing the molecular section was to interpret the biochemical, genetic, and physiological data in a context that would encourage and arouse others to
An Abbreviated Tool for Assessing Conformity to Masculine Norms: Psychometric Properties of the Conformity to Masculine Norms Inventory-46

The Conformity to Masculine Norms Inventory – 46 (Parent & Moradi, 2009) is a useful tool with which to assess masculine gender role conformity. The CMNI-46 retained and built on the psychometric strengths of the original CMNI (Mahalik et al., 2003) while offering greater efficiency at approximately half of the length of the original measure. The present study offers additional examination of the reliability, validity, and factor structure of the CMNI-46 with a sample of 255 college men. In this sample, confirmatory factor analysis results suggested acceptable fit of the posited factor structure. Evidence of reliability was garnered with Cronbach’s alphas in the good to excellent range across subscales. Correlations with convergent and discriminant validity indicators were supportive of the validity of subscale scores in this sample, but suggested some caution in interpreting scores on the Playboy subscale. Overall, the findings offered psychometric support for use of the CMNI-46 in research and practice pertaining to men and masculinity.
Higher Radix Squaring Operations Employing Left-to-Right Dual Recoding

We introduce a novel left-to-right leading digit first dual recoding of an operand for the purpose of designing the squaring operation on that operand. Our dual recoding yields an array of non-negative partial squares of size essentially one half that of a comparable multiplier partial product array for both radix-4 and radix-8 designs. For radix-8 design the 128-bit square of a 64-bit operand can be obtained from a consolidated partial square array of just 11 rows. We describe advantages of our left-to-right recoding compared to a previous right-to-left Booth-folding encoding applicable to radix-4. We also show simplifications available to the designs of a rounded floating point square operation and to a low precision approximate square.
Almost Universal Ternary Sums of Squares and Triangular Numbers

For any integer x, let T x denote the triangular number \(\frac{x(x+1)} {2}\). In this paper we give a complete characterization of all the triples of positive integers (α, β, γ) for which the ternary sums \(\alpha {x}^{2} +\beta T_{y} +\gamma T_{z}\) represent all but finitely many positive integers. This resolves a conjecture of Kane and Sun (Trans Am Math Soc 362:6425–6455, 2010, Conjecture 1.19(i)) and complete the characterization of all almost universal ternary mixed sums of squares and triangular numbers.
The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2) activation.

Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD). Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200 μM H2O2 for 6 h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI) double staining and Hoechst 33342 fluorescent staining. Reduced (GSH) and oxidized glutathione (GSSG) were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100 nM) of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.
Two Hospital Mergers on Chicago's North Shore: A Retrospective Study

We provide an in-depth analysis of the price effects of two hospital mergers that occurred in the north shore suburbs of Chicago in early 2000: Evanston Northwestern Healthcare's (ENH) purchase of Highland Park Hospital (HPH) and the merger of St. Therese Medical Center (STMC) and Victory Memorial Hospital (VMH). Using standard difference-in-differences methods with data from multiple sources, including health insurance data with actual transactions prices, we find that the ENH/HPH merger led to a large and statistically significant post-merger price increase. We find no evidence of a price increase after the STMC/VMH merger. These results are robust across data sources, control groups, and case mix adjustment methods.
Roflumilast, a Type 4 Phosphodiesterase Inhibitor, Shows Promising Adjunctive, Host-Directed Therapeutic Activity in a Mouse Model of Tuberculosis

With phosphodiesterase inhibitors (PDE-Is) showing significant promise in shortening tuberculosis treatment, we assessed the effect of roflumilast, an FDA-approved type 4 PDE-I, in both acute and chronic murine models of tuberculosis. Alone, roflumilast had no effect on lung bacillary burden and mortality. However, when roflumilast was used in combination with isoniazid, a reduction in lung bacillary burden was observed. These data suggest that roflumilast may be a good candidate for tuberculosis host-directed therapy (HDT).
La economía moral del asilo. Reflexiones críticas sobre la «crisis de los refugiados» de 2015 en Europa

Based on a reformulation of the classical concept of Moral Economy that problematizes discourses and practices of asylum, this paper poses a critical reflection of the so-called 2015 European «Refugee Crisis». It first proposes a historical scrutiny of the uses and meanings of the categories of refuge and asylum, which creates the analytical context to explore the transformations in the representations of the individuals involved in migratory movements as well as the social legitimacy of their claims. In order to do so, the paper analyzes the evolution of the right of asylum in Europe from a multiplicity of lenses —etymological, historical, geographical— as a preamble to the study of its decline in the last decades. The paper concludes that the tens of thousands of people crossing the Mediterranean from Africa and the Middle East, searching for protection, have not created any «crisis», but rather reveal to the public eye a situation that has already existed for many decades: the progressive withdrawal of European countries from the commitments acquired when signing the 1951 Geneva Convention.
Race, Imprisonment, and Education: Rethinking the School-to-Prison Pipeline

The Prison Education Project (PEP) was founded in 2011 by Professor Renford Reese of Cal Poly Pomona. Its philosophy is to utilize resources that already exist in close proximity to every state prison – i.e. college students and faculty members, and use them to motivate and equip inmates for pursuing higher education and mitigating the “negative credential.” This not only empowers the inmates as individuals, but also produces very tangible effects in the state budget (reducing recidivism by just 1% will save approximately $44 million). The PEP hopes to achieve this 1% reduction by 2015. An example of the PEP programs is the “Academic Orientation,” where students give presentations to expose inmates to college life, coursework and the possibility of careers beyond graduation. Students may also help inmates in preparing for the General Education Development (GED, a high school equivalent diploma for adults) test, by tutoring them in the humanities, math, and science. A community-based participatory research approach will be utilized to examine this particularly unique relationship between California State University (CSU) students and the California Department of Corrections and Rehabilitation (CDCR). In this project we will employ a community-based participatory research (CBPR) approach to critically examine the application and effectiveness of an innovative applied research project—connecting academic teaching & learning to real-world problem solving.
Effect of Pluronic L81, a hydrophobic surfactant, on intestinal mucosal cholesterol homeostasis

Addition of triglyceride and phospholipid to sodium taurocholate when chylomicron output was blocked by L81 did not increase lymphatic total cholesterol output or mucosal unesterified (UC) content more than with sodium taurocholate alone, but mucosal esterified cholesterol (CE) was increased slightly. In these animals with defective chylomicron formation, excess cholesterol accumulated in the intestinal mucosa mainly as CE. The mucosal cholesterol content of animals with normal chylomicron transport expanded during cholesterol and triglyceride absorption, and the expansion led to increased lymphatic secretion of CE. These animals accumulated significantly less CE in their mucosa than did rats treated with L81, but had about the same amount of mucosal UC. However, the overall uptake of cholesterol from the lumen, as determined by either radioactivity or mass of cholesterol in mucosa and lymph, was significantly less in the L81 rats. Also, more radioactive cholesterol remained in the lumen of the L81-treated rats. Finally, the data on specific activities of free and esterified cholesterol showed that the mucosal cholesterol derived from the lumen does not mix evenly with the free cholesterol pool in the enterocytes and is preferentially esterified for export in lymph as triglyceride-rich lipoprotein.
Online or Print: Which Do Students Prefer?

Many studies indicate that the format of a text, electronic or print, impacts comprehension and depth of learning, both of which are essential skills for information literacy. How cognizant are college students of this effect? When they need to read a text for academic purposes, do they express a preference for print or digital? This paper discusses a survey of reading format preferences and behaviors of 390 undergraduates at the University of California, Los Angeles (UCLA), a large public university. Results will interest librarians, educators, and technology policymakers. The simplicity of the questionnaire makes it a viable instrument for use by researchers in other language communities and cultures.
Obturator Canal Lymph Node Metastasis from Rectal Carcinoid Tumors: Total Mesorectal Excision May Be Insufficient

Optimal surgical treatment for small early rectal carcinoids is controversial. Large tumors (greater than 2 cm) and those with imaging evidence of lymph node metastasis are generally treated by low anterior resection (LAR) with total mesorectal excision (TME). We first observed and reported that midgut carcinoid with extensive mesenteric lymphadenopathy often develops alternated lymphatic drainage pathways. We hypothesize that rectal carcinoids have the same potential to develop alternated lymphatic pathways outside the mesorectal envelope, which allows tumor deposits to be missed by traditional TME. Twenty-two consecutive rectal carcinoid surgical patient charts were reviewed to determine if alternated lymphatic drainage occurred and resulted in extra-mesorectal metastasis. We attempted to identify any risk factor(s) that may lead to developing such alternated lymphatic drainage pathways. Thirteen patients underwent initial LAR with TME (13/22, 59 %) and nine underwent a staged debulking for locoregional residual disease or regional/distant metastasis after previous resection (9/22, 41 %). Fourteen (14/22, 64 %) underwent radio-guided surgery in attempt to achieve a higher level of pelvic/distant metastatic disease detection and debulking. Six patients (6/22, 27 %) had obturator canal lymph node metastases confirmed histologically. Based on our study, at least 27 % of rectal carcinoid patients may have extra-mesorectal metastasis that would be missed by the traditional TME. Radio-guided surgery can identify and remove such metastasis. The effect of having such extra-mesorectal metastasis and its surgical removal on long-term survival has yet to be determined.
Abstract A083: Modulation of the immune system as a strategy to treat EGFR mutant lung adenocarcinoma

Fifteen percent of lung adenocarcinomas harbor mutations in the Epidermal Growth Factor Receptor (EGFR). Although EGFR mutant tumors show sensitivity to specific tyrosine kinase inhibitors (TKIs) like erlotinib, resistance develops after an average of 12 months and there are currently no approved therapeutic strategies to overcome resistance. Therefore, novel approaches to delay resistance and improve patient survival are crucial. Recent discoveries in tumor immunology have revealed the potential of immune-based therapies to treat lung malignancies. In particular, immune checkpoint inhibitors such as anti-PD-1 have shown efficacy in a subset of patients with metastatic lung adenocarcinoma with minimal toxicity. These promising data led us to investigate the benefit of immune modulatory agents in EGFR mutant lung cancer. As a first step, we set out to explore the role of the immune system in this lung adenocarcinoma subset using a tetracycline-inducible mouse model of EGFR mutant lung cancer. We found, in these models, that lung-specific expression of mutant EGFR and consequent tumor formation leads to the establishment of an immunosuppressive tumor microenvironment characterized by an overall decrease in CD4 T cells, infiltration of Tregs, up-regulation of PD-1 expression on both helper and cytotoxic T cells and a diminished cytokine production by these T cells. Additionally, by flow cytometry and quantitative PCR of FACS-sorted cells, we have observed increased expression of PD-L1 on alveolar macrophages, which represent over 60% of the CD45+ cells in these tumors, suggesting an engagement of the adaptive and innate arms of the immune system to mediate immunosuppression via the PD-1/PD-L1 axis. Furthermore, when the tumor suppressor gene p53 was deleted, we observed a marked decrease in tumor infiltrating CD8 T cells when compared to p53 wild-type tumors. Currently, we are evaluating the functional role of elements of the immune system in these models to delineate their effects on tumor progression and therapeutic response. Moreover, we are investigating whether the observed immunosuppression in these tumors can be altered by immunomodulatory agents such as the anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors alone or in combination with EGFR TKIs. Citation Format: Deborah Ayeni, Ping-Chih Ho, Curtis Perry, Susan Kaech, Katerina Politi. Modulation of the immune system as a strategy to treat EGFR mutant lung adenocarcinoma. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A083.
Signatures of Walking Humans from Passive and Active Acoustic Data using Time-Varying Vector Autoregressions

A sensor fusion framework for characterizing the signature of walking targets using data collected from passive acoustic and active ultrasound sensors is investigated. We compute local estimates of the acoustic energy of the footsteps and the velocity of the torso and limbs. A time-varying vector autoregression (TV-VAR) is used to model the evolution of these signals, and captures the physical correlations between them, creating a natural data fusion across different sensor modalities. The signature is defined as a subset of the parameters from the TV-VAR model, and the quality of this feature set is evaluated using a support vector machine framework to classify multiple test subjects for both detection and discrimination applications.
Vibrational frequencies and spectroscopic constants of three, stable noble gas molecules: NeCCH+, ArCCH+, and ArCN.

The search for possible, natural, noble gas molecules has led to quantum chemical, spectroscopic analysis of NeCCH+, ArCCH+, and ArCN+. Each of these systems has been previously shown to be a stable minimum on its respective potential energy surface. However, no spectroscopic data are available for laboratory detection or interstellar observation of these species, and the interstellar medium may be the most likely place in nature where these noble gas cations are found. The bent shape of NeCCH+ is confirmed here with a fairly large dipole moment and a bright C–H stretching frequency at 3101.9 cm−1. Even if this molecule is somewhat unstable, it is likely observable now that the spectral ranges of where to look have been established. ArCCH+ is much more stable but has dim double harmonic intensities for the vibrational fundamentals and a dipole moment below 0.5 D making its rotational transitions likely buried in the astronomical weeds. Even so, ArCCH+ cannot be excluded as a possibility in laboratory experiments of hydrocarbons in argon-rich environments. ArCN+, on the other hand, has a dipole moment of greater than 3.5 D, an observable C–N stretching fundamental at 2189.6 cm−1 (4.567 microns), and a viable formation pathway through HCN, a highly-abundant interstellar molecule. Consequently, these molecules containing noble gas atoms are spectroscopically classified at high-level for the first time and may be present in observable regions of outer space.
Competition of a Different Flavor: How a Strategic Group Identity Shapes Competition and Cooperation

Using an inductive study of 41 gourmet food trucks, we develop theory about how firms form a strategic group identity that shapes both competitive and cooperative behaviors among its members. Based...
Taking the Law to Court: Citizen Suits and the Legislative Process

The institution of citizen suits is a decentralized form of public participation that allows citizens to influence the implementation of public laws in courts. How does this institution influence policymaking? This article proposes a model of citizen suits. It then analyzes how this institution influences legislative decisions. The legislature bargains to choose the budget, distributive spending, and spending on an ideologically contested public good (e.g., health care or environmental protection). I find that citizen suits enable courts to forge a compromise between opponents and proponents of the public good by responding to the diverse claims of citizens. Anticipating the mobilization of citizens in courts, legislators in turn craft more socially efficient bills, with less distributive spending, which better represent the distribution of preferences for the public good compared to when citizens have no role in the implementation of legislation.
Abstract 522: HEALS Program Implementation in African American Churches for Hypertension Control and Prevention

African Americans (AAs) living in the “Stroke Belt” (Southeastern US including northern Florida) are at elevated risk for stroke. Our long-term goal is to eliminate this ethnic/regional health disparities by targeting a major modifiable risk factor for stroke, hypertension (HTN). Here we present the results of HEALS (Healthy Eating And Living Spiritually)- a faith-based, socio-culturally tailored HTN control intervention modified from PREMIER and DASH programs for AA churches. Methods: 4 church members were trained as program leaders who delivered the 3-months intervention followed by 9 months booster sessions. AA Church members of 25-75 yrs of age with known or newly diagnosed HTN (including pre-HTN as per JNC-VII) were recruited, who received HEALS program. Results: AAs with known (84%) or newly diagnosed HTN (16%) joined the program. Majority (80%) were on anti-HTN drugs. At the baseline, only three (8%) had HTN controlled (>120/80 mm Hg), 13 (35%) had pre-HTN levels, 15 (40.5%) were stage 1 and 6 (16%) in Stage 2. After receiving 12 wks HEALS sessions, mean reduction in systolic and diastolic blood pressure were -13.64 mm Hg (p =0.005) and -6.12 mm Hg (p=0.01) respectively. The study is currently in maintenance phase. Conclusion: If successful, the findings from this study will provide much-needed information on the translation and sustainability of evidence-based lifestyle modification in HTN members in community-based settings, particularly within churches, which represent the most influential institution in the community lives of AA
State Politics, Market Economy, and Community Rights and Duties in Rural Paraguay

In the national Paraguayan land registry, Nu Pyajhu Guazu, Caazapa appears to be a community of “middle” peasants (titles are listed for landholdings from 20 to 50 hectares), and it is reported as such in the available censuses. In the community itself, the population consists of 46 registered land owners or occupants with land tenure status and 60 families without land. Since the late 1970s, land available for “squatters” has become scarce both locally and in the larger eastern frontier zone adjacent to the Brazilian border. Consequently, land has become valuable and a new importance has become attached to obtaining title for land that previously was occupied with “rights to title”.
Urban rail patrolling: a game theoretic approach

Patrol scheduling is a critical operational decision in protecting urban rail networks against terrorist activities. Designing patrols to protect such systems poses many challenges that have not been comprehensively addressed in the literature of patrol scheduling so far. These challenges include strategic attackers, dynamically changing station occupancy levels and human resource related limitations. In this paper, we develop a game theoretic model for the problem of scheduling security teams to patrol an urban mass transit rail network. Our main objective is to minimize the expected potential damage caused by terrorist activities while observing scheduling constraints. We model this problem as a non-cooperative simultaneous move game between a defender and an attacker. We then develop column generation based algorithms to find a Nash equilibrium for this game. We also present a lower bound for the value of the game which can be used to terminate the column generation algorithm when a desired solution quality is reached. We then run computational experiments to investigate the efficiency of the proposed algorithms and to gain insight about the value of the patrolling game. Our results show the efficiency of the proposed algorithms. Finally, we present results for the case of a real urban rail network.
Streptococcus Pneumoniae Meningitis Presenting as Pseudo-subarachnoid Hemorrhage (P5.125)

Objective: Demonstrate that imaging of acute bacterial meningitis may mimic acute subarachnoid hemorrhage (SAH). Background: These two neurological emergencies, acute bacterial meningitis and SAH, may have similar initial clinical and radiological presentation and require rapid diagnosis with different treatments. Of the few cases in the literature that mimic SAH, only three had bacterial meningitis. One was Streptococcus pneumoniae meningitis but with milder clinical and CSF findings than our case, as well as non-contrast head CT hyperattenuation only in the basal cistern. Design/Methods: Case report Results: A 51-year-old male presented obtunded with a few days of fever, nausea and vomiting. He had acute onset right hemiparesis and aphasia. Initial, non-contrast head CT revealed diffuse hyperattenuation of the cerebral cortex and subarachnoid space, diffuse cerebral edema and hydrocephalus with the radiologic differential of diffuse SAH versus markedly elevated CSF proteinaceous exudate. An external ventricular drain was quickly inserted with an elevated ICP of 50 cm H2O, and after 50 mL of non-bloody, cloudy fluid was drained, the ICP was reduced to 22 cm H2O. CT and MR angiography of head and neck showed no aneurysms or vascular malformations. CSF studies indicated infectious etiology – no xanthochromia, RBC 110/cu mm, nucleated cells 1065/cu mm, 90% segmented neutrophils, glucose Conclusions: This case illustrates the rare presentation of acute streptococcal meningitis with radiological findings similar to SAH, specifically with proteinaceous fluid that mimicked the presence of acute blood in the subarachnoid space. Fever remains an important clue to an infectious origin and rapid CSF analysis is often necessary to differentiate between these two conditions, leading to appropriate treatment. Disclosure: Dr. Yee has nothing to disclose. Dr. Nist has nothing to disclose. Dr. Tsao has nothing to disclose. Dr. Truong has nothing to disclose.
Construction of a Molecular Population Genetic Framework for the Characterization of Helicobacter pylori Pathogenesis by Multilocus Enzyme Electrophoresis

Helicobacter pylori is now recognized as the most common cause of gastritis. H. pylori has also been implicated in the pathogenesis of duodenal ulcer disease and gastric ulcer disease and may play an important role in the development of precursor lesions of gastric cancer. It remains unclear whether the differences in the presentation of H. pylori associated diseases are due to infection with different genetic strains of H. pylori, variation in the host response, or both. Studies attempting to identify H. pylori strains associated with specific H. pylori diseases have recently begun (e.g., chromosomal and plasmid DNA restriction endonuclease profiling analyses). DNA-DNA solution hybridization of genomic DNA from H. pylori isolates found that H. pylori isolates from patients with duodenal ulcer, on average, formed a different hybridization group from isolates from patients with asymptomatic gastritis [3]. Recent studies of many other pathogenic bacterial species have shown that genetic subpopulations of bacteria are nonrandomly associated with certain clinical disorders [2] and that, even for species that are genetically highly variable, the majority of cases of serious disease are caused by a small proportion of the total bacterial cell lineages.
EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC

Translation initiation is orchestrated by the cap binding and 43S preinitiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX mutations are enriched in advanced thyroid cancers, where they display a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer. EIF1AX-A113splice variants stabilize the PIC and induce ATF4, a sensor of cellular stress, which is co-opted to suppress EIF2α phosphorylation, enabling a general increase in protein synthesis. RAS stabilizes c-MYC, an effect augmented by EIF1AX-A113splice. ATF4 and c-MYC induce expression of amino acid transporters and enhance sensitivity of mTOR to amino acid supply. These mutually reinforcing events generate therapeutic vulnerabilities to MEK, BRD4, and mTOR kinase inhibitors. SIGNIFICANCE: Mutations of EIF1AX, a component of the translation PIC, co-occur with RAS in advanced thyroid cancers and promote tumorigenesis. EIF1AX-A113splice drives an ATF4-induced dephosphorylation of EIF2α, resulting in increased protein synthesis. ATF4 also cooperates with c-MYC to sensitize mTOR to amino acid supply, thus generating vulnerability to mTOR kinase inhibitors. This article is highlighted in the In This Issue feature, p. 151.
Getting to know you: Social media personalization as a means of enhancing brand loyalty and perceived quality

Abstract Social media has become one of the largest environments of human interaction, with more than 80% of Americans using social media and firm spending on social media marketing more than quadrupling in the past decade. Yet, little is known about the effects of ad personalization in the social media context. This research develops and tests a comprehensive model of personalized advertising in the development of consumer's brand perceptions using 242 responses collected from Amazon Mechanical Turk. Results suggest perceived personalization positively impacts consumer brand engagement and brand attachment, both enhance perceived quality and brand loyalty of brands advertised on Facebook.
Project scale and private sector environmental decision making: Factors affecting investments in small- and large-scale brownfield projects

The past decade has seen substantial policy effort directed at promoting the reclamation and reuse of urban brownfields or potentially contaminated properties. This paper is based on interviews with developers and lenders involved in redevelopment efforts. Findings indicate that effective policies and programs need to be framed within an understanding of the different needs of smaller and larger redevelopments. While market forces were equally significant inducements for both types of projects, important needs of small developers were not met. Overall, they were less likely to receive government subsidies, had greater difficulty accessing private capital, and lacked information about processes associated with remediation. Developers of large projects were more likely to benefit from public financing and were able to mobilize a network of supportive organizations to help them manage barriers to project completion. Additional findings suggest problems with legal mechanisms intended to promote brownfields cleanup in the course of redevelopment. While lender financing and public involvement of large projects encouraged environmentally responsible behaviors, self-financing of small redevelopments permitted some developers to skirt environmental requirements and avoid cleanup altogether. The paper ends with a discussion of the value of placing greater public emphasis on small projects and offers suggestions for policies to address their needs.
Nonlinear structural stability performance of pressurized thin-walled FGM arches under temperature variation field

Abstract This paper focuses on the elastic structural stability analysis of the pressurized thin-walled functionally graded material (FGM) arches under temperature variation field. The material properties are temperature-dependent and thermo-elastic. The total potential energy function of the pinned–pinned arch was expressed explicitly by employing the classical thin-walled arch theories and admissible radial displacement functions. By means of the variational principle, the expressions of the critical buckling pressure were obtained analytically and verified numerically by developing a two-dimensional (2D) simulated model. The pre- and post-buckling equilibrium paths were depicted to explore the maximum pressure (buckling pressure). The comparison showed that the numerical results were in excellent agreement with the analytical solutions for different subtended angles, volume fraction exponents and temperature variations. In the end, the effects of volume fraction exponent and temperature variation were examined on the critical buckling pressure, the bending moment, the hoop force, the hoop strain and stress, the hoop and radial displacement components through the whole arch.
Novel Role of Macrophage Migration Inhibitory Factor in Upstream Control of the Unfolded Protein Response After Ethanol Feeding in Mice

Background Macrophage migration inhibitory factor (MIF), a pluripotent immune regulator, is an emerging mediator in alcohol-related liver disease (ALD). MIF is associated with ALD progression through its chemokine- and cytokine-like activities. Methods Mechanistic studies into the role of MIF in ethanol (EtOH)-induced liver injury were performed in Mif-/- mice and in C57BL/6J mice treated with a small-molecule MIF antagonist, MIF098, after Gao-Binge (acute-on-chronic) EtOH feeding, an EtOH feeding protocol associated with hepatic neutrophilia and induction of the unfolded protein response (UPR). Results The MIF axis, for example, MIF and MIF receptors invariant polypeptide of major histocompatibility complex, class II antigen-associated (CD74), CXCR2, CXCR4, and CXCR7, was enhanced in the livers of alcoholic hepatitis (AH) patients as compared to healthy controls. Mif-/- mice were protected from hepatocellular injury after Gao-Binge feeding, independent of neutrophilia and inflammation, but were associated with the UPR. Interestingly, the UPR signature in AH patients and in mice following Gao-Binge feeding was biased toward cell death with increased expression of pro-cell death CCAAT-enhancer-binding protein homologous protein (CHOP) and decreased prosurvival GRP78. The UPR and liver injury 6 hours after binge were prevented both in Mif-/- mice and in MIF098-treated mice. However, both MIF interventions led to increased liver injury and exacerbated the hepatic UPR 9 hours after binge. Induction of upstream UPR signaling and expression of CHOP protein by thapsigargin in alpha mouse liver 12 hepatocytes were blunted by coexposure to MIF098, directly connecting MIF to UPR in hepatocytes. Conclusions The current study revealed that, in addition to its cytokine/chemokine functions, MIF is an upstream regulator of UPR in response to EtOH feeding in mice. Importantly, both MIF and UPR can either protect or contribute to liver injury, dependent upon the stage or severity of EtOH-induced liver injury.
Online Distributed Analytics at the Edge with Multiple Service Grades

In this paper, we study the problem of how to allocate bandwidth and computation resources to deliver data analytics services at the edge. The types of services we envision consist of a chain of tasks that must be carried out sequentially, and where the number of tasks executed in the chain determines the grade in which a service is delivered. An example of such type of service is video analytics where different deep-learning algorithms are combined to provide a more accurate description of a scene. The contributions of the paper are to formulate the static resource allocation problem as a linear program, to discuss the challenges of static formulations in dynamic settings, and to propose a control-type formulation that uses approximate system dynamics and time-varying cost functions. The work also highlights the need for policies that can operate the network and learn its characteristics simultaneously.
Aurora B Kinase Promotes CHIP-Dependent Degradation of HIF1α in Prostate Cancer Cells

Hypoxia is a major factor in tumor progression and resistance to therapies, which involves elevated levels of the transcription factor HIF1α. Here, we report that prostate tumor xenografts express high levels of HIF1α and show greatly enhanced growth in response to knockdown of the E3 ligase CHIP (C-terminus of Hsp70-interacting protein). In multiple human prostate cancer cell lines under hypoxia, taxol treatment induces the degradation of HIF1α, and this response is abrogated by knockdown of CHIP, but not by E3 ligase VHL or RACK1. HIF1α degradation is accompanied by loss of function, evidenced by reduced expression of HIF1α-dependent genes. CHIP-dependent HIF1α degradation also occurs in cells arrested in mitosis by nocodazole instead of taxol. Mitotic kinase Aurora B activity is required for taxol-induced HIF1α degradation. Purified Aurora B directly phosphorylates HIF1α at multiple sites, and these modifications enhance its polyubiquitination by CHIP in a purified reconstituted system. Our results show how activation of Aurora B promotes CHIP-dependent degradation of HIF1α in prostate cancer cells. This new knowledge may affect the use of mitotic kinase inhibitors and open new approaches for treatment of hypoxic prostate tumors.
Long-range exciton transport and slow annihilation in two-dimensional hybrid perovskites.

Two-dimensional hybrid organic-inorganic perovskites with strongly bound excitons and tunable structures are desirable for optoelectronic applications. Exciton transport and annihilation are two key processes in determining device efficiencies; however, a thorough understanding of these processes is hindered by that annihilation rates are often convoluted with exciton diffusion constants. Here we employ transient absorption microscopy to disentangle quantum-well-thickness-dependent exciton diffusion and annihilation in two-dimensional perovskites, unraveling the key role of electron-hole interactions and dielectric screening. The exciton diffusion constant is found to increase with quantum-well thickness, ranging from 0.06 ± 0.03 to 0.34 ± 0.03 cm2 s−1, which leads to long-range exciton diffusion over hundreds of nanometers. The exciton annihilation rates are more than one order of magnitude lower than those found in the monolayers of transition metal dichalcogenides. The combination of long-range exciton transport and slow annihilation highlights the unique attributes of two-dimensional perovskites as an exciting class of optoelectronic materials. Two-dimensional hybrid perovskites are promising excitonic materials; however, there currently lacks understanding on exciton diffusion and annihilation. Here Deng et al. employ transient absorption microscopy to disentangle quantum-well-thickness-dependent exciton transport and annihilation in these materials.
Chandra X-ray Spectroscopic Imaging of Sgr A* and the Central Parsec of the Galaxy

We present results of our Chandra observation with the ACIS-I instrument centered on the position of Sagittarius A* (Sgr A*), the compact nonthermal radio source associated with the massive black hole (MBH) at the dynamical center of the Milky Way Galaxy. We have obtained the first high-spatial-resolution (~1 arcsec), hard X-ray (0.5-7 keV) image of the central 40 pc (17 arcmin) of the Galaxy and have discovered an X-ray source, CXOGC J174540.0-290027, coincident with the radio position of Sgr A* to within 0.35 arcsec, corresponding to a maximum projected distance of 16 light-days for an assumed distance to the center of the Galaxy of 8.0 kpc. We received 222 +/-17 (1 sigma) net counts from the source in 40.3 ks. Due to the low number of counts, the spectrum is well fit either by an absorbed power-law model with photon index Gamma = 2.7 (1.8-4.0) and column density NH = (9.8 [6.8-14.2]) x 10^22 cm^-2 (90% confidence interval) or by an absorbed optically thin thermal plasma model with kT = 1.9 (1.4-2.8) keV and NH = (11.5 [8.4-15.9]) x 10^22 cm^-2. Using the power-law model, the measured (absorbed) flux in the 2-10 keV band is (1.3 [1.1-1.7]) x 10^-13 ergs cm^-2 s^-1, and the absorption-corrected luminosity is (2.4 [1.8-5.4]) x 10^33 ergs s^-1. We also briefly discuss the complex structure of the X-ray emission from the Sgr A radio complex and along the Galactic plane and present morphological evidence that Sgr A* and Sgr A West lie within the hot plasma in the central cavity of Sgr A East.
No Change in the Use of Antivenom in Copperhead Snakebites in Ohio.

Introduction Historically, copperhead snake (Agkistrodon contortrix) envenomations were not treated with antivenom owing to related adverse events and little benefit. However, recent studies have shown improved outcomes with antivenom use. We hypothesized that the frequency of antivenom use for copperhead envenomation in Ohio has increased as benefits of administration became more widely known. Methods All copperhead snakebites reported to the Ohio poison control centers from 2006 through 2016 were compiled. Antivenom use, bite severity, and disposition were abstracted. A nonparametric test for trend was used to evaluate changes over time for the number of patients treated with antivenom and patient disposition. Logistic regression was used to assess the odds of admission vs discharge with antivenom administration, bite severity, age, and sex as independent variables. Results Ninety-eight patients reported copperhead snakebites to the poison control centers. The test of trend showed no change in the proportion of patients treated with antivenom by year (P=0.42). There was no difference in the proportion of patients discharged home (P=0.38) per year. Logistic regression showed antivenom use was associated with an odds ratio for admission of 46.7 (95% CI: 7.3–296.4). Conclusions The frequency of antivenom use for copperhead bites did not significantly increase between 2006 and 2016. Administration of antivenom was associated with a large increase in the odds of admission to the hospital, even when controlling for bite severity. Further education regarding the benefits and safety of antivenom may increase its use for copperhead snakebites, but may lead to an increase in hospital admissions.
Extracellular calcium alters calcium-sensing receptor network integrating intracellular calcium-signaling and related key pathway.

G-protein-coupled receptors (GPCRs) are a target for over 34% of current drugs. The calcium-sensing receptor (CaSR), a family C GPCR, regulates systemic calcium (Ca2+) homeostasis that is critical for many physiological, calciotropical, and noncalciotropical outcomes in multiple organs. However, the mechanisms by which extracellular Ca2+ (Ca2+ex) and the CaSR mediate networks of intracellular Ca2+-signaling and players involved throughout the life cycle of CaSR are largely unknown. Here we report the first CaSR protein–protein interactome with 94 novel putative and 8 previously published interactors using proteomics. Ca2+ex promotes enrichment of 66% of the identified CaSR interactors, pertaining to Ca2+ dynamics, endocytosis, degradation, trafficking, and primarily to protein processing in the endoplasmic reticulum (ER). These enhanced ER-related processes are governed by Ca2+ex-activated CaSR which directly modulates ER-Ca2+ (Ca2+ER), as monitored by a novel ER targeted Ca2+-sensor. Moreover, we validated the Ca2+ex dependent colocalizations and interactions of CaSR with ER-protein processing chaperone, 78-kDa glucose regulated protein (GRP78), and with trafficking-related protein. Live cell imaging results indicated that CaSR and vesicle-associated membrane protein-associated A (VAPA) are inter-dependent during Ca2+ex induced enhancement of near-cell membrane expression. This study significantly extends the repertoire of the CaSR interactome and reveals likely novel players and pathways of CaSR participating in Ca2+ER dynamics, agonist mediated ER-protein processing and surface expression.
The Recombination Enhancer Modulates the Conformation of Chr. III in Budding Yeast: A Dissertation

A hierarchy of different chromosome conformations plays a role in many biological systems. These conformations contribute to the regulation of gene expression, cellular development, chromosome transmission, and defects can lead to human disease. The highest functional level of this hierarchy is the partitioning of the genome into compartments of active and inactive chromatin domains (1’s -10’s Mb). These compartments are further partitioned into Topologically Associating Domains (TADs) that spatially cluster co-regulated genes (100’s kb – 1’s Mb). The final level that has been observed is long range loops formed between regulatory elements and promoters (10’s kb – 100’s Mb). At all of these levels, mechanisms that establish these conformations remain poorly understood. To gain new insights into processes that determine chromosome folding I used the mating type switching system in budding yeast to study the chromosome conformation at length scales analogous to looping interaction. I specifically examined the role in chromosome conformation in the mating type switching system. Budding yeast cells can have two sexes: MATa and MATα. The mating types are determined by allele-specific expression of the MAT locus on chromosome III. The MATa allele encodes for transcription factors responsible for the MATa mating type and the MATα allele encodes transcription factors responsible for the MATα mating type. Yeast cells can switch their mating type by a process that repairs a break at MAT using one of two silent loci, HML or HMR, as a donor to convert the allele at the MAT locus. When MATa