cssi/SciSciGPT-SciSciNet huggingface dataset:
Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis

G protein coupled receptors (GPCRs) are one of the most widely studied gene superfamilies. Thousands of GPCR research studies have utilized heterologous expression systems such as human embryonic kidney cells (HEK293). Though often treated as 'blank slates', these cell lines nevertheless endogenously express GPCRs and related signaling proteins. The outcome of a given GPCR study can be profoundly influenced by this largely unknown complement of receptors and/or signaling proteins. Little easily accessible information exists that describes the expression profiles of the GPCRs in cell lines. What is accessible is often limited in scope - of the hundreds of GPCRs and related proteins, one is unlikely to find information on expression of more than a dozen proteins in a given cell line. Microarray technology has allowed rapid analysis of mRNA levels of thousands of candidate genes, but though often publicly available, the results can be difficult to efficiently access or even to interpret. To bridge this gap, we have used microarrays to measure the mRNA levels of a comprehensive profile of non-chemosensory GPCRs and over a hundred GPCR signaling related gene products in four cell lines frequently used for GPCR research: HEK293, AtT20, BV2, and N18. This study provides researchers an easily accessible mRNA profile of the endogenous signaling repertoire that these four cell lines possess. This will assist in choosing the most appropriate cell line for studying GPCRs and related signaling proteins. It also provides a better understanding of the potential interactions between GPCRs and those signaling proteins.
Bridging the Gap: From 2D Cell Culture to 3D Microengineered Extracellular Matrices

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, techniques for micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels will be discussed in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues.
Seasonal and Cross-Seasonal Timing of Fungicide Trunk Injections in Apple Trees to Optimize Management of Apple Scab

To optimize the number and timing of trunk injections for season-long control of apple scab (Venturia inaequalis), we evaluated 1 to 2 and 4 seasonal and cross-seasonal injections of potassium phosphites and synthetic fungicides and quantified residues in leaves and fruit. Phosphites accumulated in the canopy at the highest concentrations, aligned well in time with scab suppression, and gave better leaf scab control of 41.8 to 73.5% than propiconazole (16.9 to 51.5%) or cyprodinil + difenoconazole (5.4 to 17.4%). More injections of phosphites controlled leaf scab better than fewer (23.7% versus 48.2%), and more fungicide injections resulted in 21.9 to 51.1% better leaf scab control than fewer. Leaf scab control with phosphites was only 3.2 to 13.9% better with 4 cross-seasonal compared with 4 seasonal injections, while 1 to 2 seasonal compared with 1 to 2 cross-seasonal injections improved scab control only for 4.2 to 22.1%. On shoots, injected phosphites provided comparable or for 4.4 to 10.5% and 22.3 to 41.4% better scab control than spray standards. On fruit, injected phosphites slightly improved control compared with sprayed phosphites or the sprayed fungicide standard (33.4 to 40.8%). Two seasonal injections of phosphites controlled shoot scab 5.7% better than 9 spray applications. Five sprays of cyprodinil + difenoconazole controlled scab better than their injections. Fruit residues of phosphites reached 2.8 ppm and declined in all treatments except in 2 seasonal injections and phosphite sprays. Cyprodinil and difenoconazole fruit residues reached 0.02 and 0.07 ppm and declined sharply toward the end of the season. These were far below the United States, Codex, and EU MRL-s of 1, 0.8, and 0.5 ppm for difenoconazole, and 1.7, 2, and 1 ppm for cyprodinil, respectively.
Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated, and cultured cells.

Antioxidant enzyme activities, H2O2 clearance, and H2O2 generation by rat alveolar epithelial type II cells were compared between in situ, freshly isolated (6 h ex vivo), and cultured cells (48 h ex vivo). Immunocytochemical studies did not show changes in catalase, Mn superoxide dismutase, or CuZn superoxide dismutase labeling density in cytoplasm, peroxisomes, or mitochondria. Numbers of peroxisomes and mitochondria per cell decreased in cultured cells. Biochemical studies showed that cell culture resulted in a significant decrease in activities of catalase (49%), glutathione reductase (50%), glutathione peroxidase (74%), and in the capacity of the cells to scavenge extracellular H2O2. Addition of the specific catalase inhibitor, aminotriazole, decreased the rate of consumption of exogenously added H2O2 in freshly isolated cells but not in cultured cells. Neither aminotriazole nor 1,3-bis (2-chloroethyl)-1-nitrosourea, which inactivates glutathione reductase, altered H2O2 consumption by cultured cells. The rate of extracellular H2O2 release in both freshly isolated and cultured cells was 0.71 nmol.min-1.mg protein-1. It can be concluded that levels of some antioxidant enzymes fall in cultured alveolar epithelial type II cells, and that, although catalase likely plays a significant role in protection of freshly isolated cells against oxidant stress, this pathway may be less important after culture.
Trp-Cage Folding on Organic Surfaces

Trp-cage is an artificial miniprotein that is small, stable, and fast folding due to concerted hydrophobic shielding of a Trp residue by polyproline helices. Simulations have extensively characterized Trp-cage; however, the interactions of Trp-cage with organic surfaces (e.g., membranes) and their effect on protein conformation are largely unknown. To better understand these interactions we utilized a combination of replica-exchange molecular dynamics (REMD) and metadynamics (MetaD), to investigate Trp-cage folding on self-assembled monolayers (SAMs). We found that, with REMD and MetaD, Trp-cage strongly binds to neutral CH3 surfaces (-25kT) and moderately adsorbs to anionic COOH interfaces (-7.6kT), with hydrophobic interactions driving CH3 adhesion and electrostatic attractions driving COOH adhesion. Similar to solid-state surfaces, SAMs facilitate a number of intermediate Trp-cage conformations between folded and unfolded states. Regarding Trp-cage's aromatic groups in neutral CH3 systems, Tyr becomes oriented parallel to the surface in order to maximize hydrophobic interactions while Trp remains caged perpendicular to the surface; however, Trp can reorient itself parallel to the interface as the miniprotein more closely binds to the surface. In contrast, Tyr and Trp are both repelled from COOH surfaces, though the Trp-cage still adheres to the anionic interface via Lys and its N-terminated Asn residue.
Understanding Blood Pressure Variation and Variability: Biological Importance and Clinical Significance

Variability is a normative property of blood pressure necessary for survival which likely contributes to morbidity and mortality through allostatic load. Because of its allostatic and adaptive properties blood pressure responses to peculiar situations like the visit to the clinic can lead to the misdiagnosis of hypertension. Cuff methods of blood pressure measurement can also create blood pressure variation when there really is none. There are also physiological differences between populations related to their evolutionary history that likely further affect the extent of population differences in 24-h blood pressure variability. Quantifying the sources and extent of blood pressure variability can be done using natural experimental models and through the evaluation of ecological momentary data. It is very likely that the results of population studies of blood pressure variability and morbidity and mortality risk are inconclusive because the parameters used to assess blood pressure variability do not reflect the actual nature of blood pressure allostasis.
Estrogen Receptors Modulation of Anxiety-Like Behavior

Estrogens exert profound effects on the expression of anxiety in humans and rodents; however, the directionality of these effects varies considerably within both clinical and preclinical literature. It is believed that discrepancies regarding the nature of estrogens’ effects on anxiety are attributable to the differential effects of specific estrogen receptor (ER) subtypes. In this chapter we will discuss the relative impact on anxiety and anxiety-like behavior of each of the three main ERs: ERα, which has a generally anxiogenic effect, ERβ, which has a generally anxiolytic effect, and the G-protein-coupled ER known as GPR30, which has been found to both increase and decrease anxiety-like behavior. In addition, we will describe the known mechanisms by which these receptor subtypes exert their influence on emotional responses, focusing on the hypothalamic–pituitary–adrenal axis and the oxytocinergic and serotonergic systems. The impact of estrogens on the expression of anxiety is likely the result of their combined effects on all of these neurobiological systems.
Allergic Acute Coronary Syndrome (Kounis Syndrome)

Consider this diagnosis in any patient with suspected/proven acute coronary syndrome and concurrent allergic manifestations, eg, pruritus, hives, wheezing
When do sell-side analysts switch industries they follow?

ABSTRACTBetween 1984 and 2014 over 3400 sell-side analysts changed the primary industry they followed. This article documents that analysts are more likely to change their industries when their absolute and relative forecasting accuracy in that industry is low and when the accuracy in the new industry is high. Analysts are more likely to switch industries at the beginning of their careers, after a recent change of an employing brokerage house, and if they have a history of switching industries before. Analysts are less likely to make a switch when their forecasting activity in the industry is high, when the industry is followed by many analysts and when they are employed by a top brokerage house.
On the construction of set-based meanings for the truth of mathematical conditionals

Abstract This paper presents a case study of Hugo’s construction of Euler diagrams to develop set-based meanings for the truth of mathematical conditionals. We use this case to set forth a framework of three stages of activity in students’ guided reinvention of mathematical logic: reading activity, connecting activity, and fluent activity. The framework also categorizes various forms of connecting activity by which students may reflect on their reading activity: connecting tasks, connecting representations, and connecting conditions for truth and falsehood (which we call meanings). We argue that coordinating such connections is necessary to justify logical equivalences, such as why contrapositive statements share truth-values. Through the case study, we document the representations and meanings that Hugo called upon to assign truth-values to conditionals. The framework should help clarify and advance future research on the teaching and learning of logic rooted in students’ mathematical activity.
Estimating nitrate-nitrogen retention in a large constructed wetland using high-frequency, continuous monitoring and hydrologic modeling

Abstract Wetlands are an effective edge-of-field conservation practice for reducing agricultural nitrate-nitrogen (NO3-N) loads, but their removal performance varies with hydrologic conditions and other factors difficult to capture with traditional grab sampling schemes. We quantified NO3-N retention in a large Iowa constructed wetland using high-frequency (15-min) in situ NO3-N sensors and a physically-based hydrologic model that estimated discharge. Monitoring from May–Nov over a 3-yr period (2014–16) indicated the wetland reduced incoming NO3-N concentrations 49% and loads by an estimated 61 kg day−1 (0.48 g m−2 day−1 based on wetland area removal). Monthly and seasonal (May–Nov) wetland retention performance were significantly influenced by hydrologic conditions, as NO3-N concentration reductions ranged from 23% in a year that received nearly 50% more seasonal precipitation than average (2016) to 59–65% in years that received average seasonal precipitation (2014–15). On a monthly basis, NO3-N mass retention was highest in Jun when NO3-N loading was highest, while retention efficiency – the percent of the incoming NO3-N load retained by the wetland – was highest in Jul and Aug when water temperature and hydraulic residence time were higher. The high-frequency monitoring captured NO3-N dynamics not possible with lower-frequency sampling. Extrapolating the May–Nov 3-yr average wetland NO3-N retention estimated in this study to a much larger scale, over 5600 wetlands treating more than 60% of Iowa’s area and totaling an estimated $1.5 billion in design and construction would be required to reduce the state’s baseline NO3-N load by 45%, indicating the sizable investment in wetland construction and restoration needed to achieve Gulf of Mexico Hypoxia water quality goals.
Alkylaluminum Halide Induced Reactions of Carbonyl Compounds with Unactivated Alkenes

Aldehydes, ketones and α,β-unsaturated aldehydes and ketones undergo a wide variety of reactions with unactivated alkenes in the presence of alkylaluminum halide catalysts. Ene reactions, Diels-Alder reactions, Prins reactions and cation-olefin addition reactions occur depending on the choice of substrate and Lewis acid.
Urban forested parks and tall tree canopies contribute to macrolichen epiphyte biodiversity in urban landscapes

Abstract Land use changes through urbanization can dramatically impact floral and faunal species-specific survival and alter patterns of regional biodiversity. These changes can lead to complex, ecosystem scale interactions that yield both positive and negative impacts on urban and ex-urban biota. The Pacific Northwest region is one of the most rapidly urbanizing areas of the United States, with the human population estimated to increase more than fifty percent by 2050. Despite rapid population growth in the Pacific Northwest and a forest system known to provide extraordinary ecosystem services, relatively little is known about how human activities affect urban tree biology and the services these trees provide. Specifically, little is known about how urbanization impacts tall tree canopy epiphyte communities, a unique and sensitive component of Pacific Northwest trees which are known to contribute essential ecosystem functions. Here, we revisit a historic study of urban epiphytic lichen communities, initially conducted 18 years ago in Portland, Oregon, USA. Additionally, to compare ground and canopy-based survey methods and to gain a broader understanding of urban epiphytic communities, we comprehensively investigated the biodiversity of stratified urban canopy epiphyte lichen communities, for the first time. Our results show that tall, urban conifer trees and urban parks and forested areas can provide both heterogeneous and stratified habitats for urban-tolerant epiphytic lichens. We found significant and highly eutrophied lichen communities in all epiphytic surveys, suggesting that continued urbanization in the Portland metro region may further impact these communities despite overall gains in regional air quality during the 18 year study period. Our results support the distinct homogenization of urban epiphytic lichen communities, suggesting that it may be necessary to expand beyond measures of biodiversity to consider community composition and functional biodiversity in assessments of the ecology and potential ecosystem services of epiphyte communities within urbanizing landscapes.
The completeness characterization of $$C(\mathcal {L})$$ C ( L ) , $$\mathcal {L}$$ L a locale

The result of the title is: an archimedean $$\ell $$ -group with weak unit A is (isomorphic to) $$C(\mathcal {L})$$ for some (identifiable) locale $$\mathcal {L}$$ (or, $$\mathbb {R}\mathcal {L}^{\mathrm {op}}$$ , $$\mathcal {L}^{\mathrm {op}}$$ the opposite frame) iff A is divisible and “ $$*$$ -complete,” (a type of sequential completeness). This is from Ball and Hager (Positivity 10:165–199, 2006), and is revisited here, with streamlined proof.
Alpha-2 adrenergic receptors in the bovine retina : presence of only the alpha-2D subtype

Purpose. To identify and characterize the alpha-2 adrenergic receptor subtypes present in the bovine neurosensory retina. Methods. Radioligand saturation and inhibition binding assays were performed with the antagonist radioligands [ 3 H] RX82 1002 and [ 3 H]rauwolscine. Results. [ 3 H]RX821002 bound to a single class of receptors with the characteristics of an alpha-2 adrenergic receptor with an affinity (K D ) of 0.16 nM and a receptor density (B max ) of 1500 fmol/mg protein. Correlation of the affinities (pi values) for nine antagonists in the bovine neurosensory retina with the alpha-2D receptor of the bovine pineal gave a correlation coefficient of 0.99. The correlation coefficients for the alpha-2A (0.84), alpha-2B (0.36), and alpha-2C (0.39) subtypes were much lower. The presence of a minor population of alpha-2B or alpha-2C receptors was excluded. Conclusions. A high density of alpha-2D adrenergic receptors is present in the bovine neurosensory retina. Neither the alpha-2B nor the alpha-2C subtype is detectable. Invest Ophthalmol Vis Sci. 1995 ;36 :1885-1892.
Comparing Surface and Intramuscular Electromyography for Simultaneous and Proportional Control Based on a Musculoskeletal Model: A Pilot Study

Simultaneous and proportional control (SPC) of neural-machine interfaces uses magnitudes of smoothed electromyograms (EMG) as control inputs. Though surface EMG (sEMG) electrodes are common for clinical neural-machine interfaces, intramuscular EMG (iEMG) electrodes may be indicated in some circumstances (e.g., for controlling many degrees of freedom). However, differences in signal characteristics between sEMG and iEMG may influence SPC performance. We conducted a pilot study to determine the effect of electrode type (sEMG and iEMG) on real-time task performance with SPC based on a novel 2-degree-of-freedom EMG-driven musculoskeletal model of the wrist and hand. Four able-bodied subjects and one transradial amputee performed a virtual posture matching task with either sEMG or iEMG. There was a trend of better task performance with sEMG than iEMG for both able-bodied and amputee subjects, though the difference was not statistically significant. Thus, while iEMG may permit targeted recording of EMG, its signal characteristics may not be as ideal for SPC as those of sEMG. The tradeoff between recording specificity and signal characteristics is an important consideration for development and clinical implementation of SPC for neural-machine interfaces.
Synthetic Bio-Graphene Based Nanomaterials through Different Iron Catalysts

Kraft lignin was catalytically graphitized to graphene-based nanostructures at 1000 °C under argon atmosphere with four iron catalysts, iron(III) nitrate (Fe-N); iron(II) chloride (Fe-Cl2); iron(III) chloride (Fe-Cl3); and iron(II) sulfate (Fe-S). The catalytic decomposition process of iron-promoted lignin materials was examined using thermalgravimetric analysis and temperature-programmed decomposition methods. The crystal structure, morphology and surface area of produced materials were characterized by means of X-ray diffraction, Raman, scanning electron microscopy, high resolution transmission electron microscopy and N2 adsorption−desorption techniques. Experimental results indicated that iron nitrate catalyst had better iron dispersion three other iron salts. Iron nitrate was the most active catalyst among four iron salts. The low activity of iron in iron chloride-promoted samples was because the residual chlorine over iron surfaces prevent iron interaction with lignin functional groups.
Actionable Objective Optimization for Suspicious Behavior Detection on Large Bipartite Graphs

We have been spotting massive suspicious behaviors on bipartite graph-based applications such as social networks and e-commercial platforms. Existing detection methods estimate the suspiciousness score of source users (e.g., followers, buyers) assuming that the behavioral patterns of suspicious source users (e.g., botnet followers, bully buyers) lead to abnormal high density in the graphs. A serious issue when putting the methods into real use is the false positives – the platforms cannot automatically suspend the source users just based on their suspiciousness scores. In this work, we revisit the problem of suspicious behavior detection from the perspective of the target users (e.g., followees, sellers), and provide them an effective and actionable solution using big behavior data analytics. We propose a novel method called Actionable Objective Optimization in which the variables are the target users’ decisions rather than source users’ scores. Experimental results show that our proposed actionable method consistently outperforms the state-of-the-art methods.
A Perspective on Interaction Tests in Genetic Association Studies

The identification of gene-gene and gene-environment interaction in human traits and diseases is an active area of research that generates high expectation, and most often lead to high disappointment. This is partly explained by a misunderstanding of some of the inherent characteristics of interaction effects. Here, I untangle several theoretical aspects of standard regression-based interaction tests in genetic association studies. In particular, I discuss variables coding scheme, interpretation of effect estimate, power, and estimation of variance explained in regard of various hypothetical interaction patterns. I show first that the simplest biological interaction models—in which the magnitude of a genetic effect depends on a common exposure—are among the most difficult to identify. Then, I demonstrate the demerits of the current strategy to evaluate the contribution of interaction effects to the variance of quantitative outcomes and argue for the use of new approaches to overcome these issues. Finally I explore the advantages and limitations of multivariate models when testing for interaction between multiple SNPs and/or multiple exposures, using either a joint test, or a test of interaction based on risk score. Theoretical and simulated examples presented along the manuscript demonstrate that the application of these methods can provide a new perspective on the role of interaction in multifactorial traits.
Storage Requirements and Costs of Shaping Renewable Energy Toward Grid Decarbonization

Summary Deeply decarbonizing electricity production will likely require that low-carbon sources meet energy demand throughout days, years, and decades. Wind and solar energy are possible low-carbon options, but resource variability can limit their reliability. Storage can help address this challenge by shaping intermittent resources into desired output profiles. But can solar and wind energy with storage cost-competitively fulfill this role? How do diverse storage technologies compare? We address these questions by analyzing systems that combine wind and solar energy with storage to meet various demand profiles. We estimate that energy storage capacity costs below a roughly $20/kWh target would allow a wind-solar mix to provide cost-competitive baseload electricity in resource-abundant locations such as Texas and Arizona. Relaxing reliability constraints by allowing for a few percent of downtime hours raises storage cost targets considerably, but would require supplemental technologies. Finally, we discuss storage technologies that could reach the estimated cost targets.
Deciphering ocular diseases on an epigenetic platform

Abstract Eyes are one of the most complex organs in our body; the sense of sight is the most appreciated senses and 90% of all information is acquired through vision. However, eyes are constantly exposed to the environmental factors like pollutants, bacteria, and ultraviolet radiations, leading to various ocular disorders including cataract, age-related macular degeneration, glaucoma, and retinopathy. These diseases also have a complex etiology involving many molecular/biochemical and functional abnormalities. Gene activity can be regulated by epigenetic modifications. These modifications are influenced by external factors, and they do not alter the DNA sequence. Cutting edge research continues to produce mounting evidence of an association between epigenetic modifications and various ocular diseases. How to detect epigenetic changes and how to rescue them, however, remains one of the biggest challenges. This chapter outlines the current understanding of the role of epigenetic modifications, and their possible use as a biomarker of chronic ocular diseases.
Rhetoric and feminism in the Cárcel de Amor 1

In the debate between misogyny and feminism in fifteenth-century Spain, Diego de San Pedro's Carcel de Amor unequivocally and uncompromisingly comes to the defence of the female sex.2 The most obvi...
Evolution of the Properties of SAC-Bi-Ni-Sb Lead Free Solder During Mechanical Cycling

Solder joints in electronic packages often experience fatigue failures due to cyclic mechanical stresses and strains in fluctuating temperature environments. These stresses and strains induced by mismatches in coefficients of thermal expansion lead to damage accumulation and contribute to the crack initiation, crack propagation, and eventually to failure. In this study, we have investigated the cyclic stressstrain behavior of a six element lead free solder alloy SAC-BiNi-Sb (Innolot) optimized for high temperature automotive applications. The main purpose of this work was to investigate the accumulation of damage in this solder material during mechanical cycling. Circular cross-sectioned solder specimens were first reflowed, and these samples were then mechanically cycled for various durations using a Micro-Mechanical tester. Cyclic stress-strain, monotonic stress-strain, and creep tests were then conducted on the prior cycled samples. The cyclic stress-strain curves obtained were studied to observe the degradation of hysteresis loop properties (peak stress, hysteresis loop area, and plastic strain range) with cycling. The monotonic stress-strain and creep test data were plotted, and various mechanical properties were characterized for various levels of cycling. Using the data from the various tests, we have been able to characterize and quantify the cycling induced damage through the observed degradations of several mechanical properties (elastic modulus, yield strength, ultimate strength, and creep strain rate) with the amount of prior cycling. The measured data for the SAC-Bi-Ni-Sb solder were compared to the results from our previous studies conducted on SAC305 and SAC+Bi (SAC_Q) lead free alloys.
Protein synthesis inhibitors stimulate MondoA transcriptional activity by driving an accumulation of glucose 6-phosphate.

Protein synthesis is regulated by the availability of amino acids, the engagement of growth factor signaling pathways, and adenosine triphosphate (ATP) levels sufficient to support translation. Crosstalk between these inputs is extensive, yet other regulatory mechanisms remain to be characterized. For example, the translation initiation inhibitor rocaglamide A (RocA) induces thioredoxin-interacting protein (TXNIP). TXNIP is a negative regulator of glucose uptake; thus, its induction by RocA links translation to the availability of glucose. MondoA is the principal regulator of glucose-induced transcription, and its activity is triggered by the glycolytic intermediate, glucose 6-phosphate (G6P). MondoA responds to G6P generated by cytoplasmic glucose and mitochondrial ATP (mtATP), suggesting a critical role in the cellular response to these energy sources. TXNIP expression is entirely dependent on MondoA; therefore, we investigated how protein synthesis inhibitors impact its transcriptional activity. We investigated how translation regulates MondoA activity using cell line models and loss-of-function approaches. We examined how protein synthesis inhibitors effect gene expression and metabolism using RNA-sequencing and metabolomics, respectively. The biological impact of RocA was evaluated using cell lines and patient-derived xenograft organoid (PDxO) models. We discovered that multiple protein synthesis inhibitors, including RocA, increase TXNIP expression in a manner that depends on MondoA, a functional electron transport chain and mtATP synthesis. Furthermore, RocA and cycloheximide increase mtATP and G6P levels, respectively, and TXNIP induction depends on interactions between the voltage-dependent anion channel (VDAC) and hexokinase (HK), which generates G6P. RocA treatment impacts the regulation of ~ 1200 genes, and ~ 250 of those genes are MondoA-dependent. RocA treatment is cytotoxic to triple negative breast cancer (TNBC) cell lines and shows preferential cytotoxicity against estrogen receptor negative (ER−) PDxO breast cancer models. Finally, RocA-driven cytotoxicity is partially dependent on MondoA or TXNIP. Our data suggest that protein synthesis inhibitors rewire metabolism, resulting in an increase in mtATP and G6P, the latter driving MondoA-dependent transcriptional activity. Further, MondoA is a critical component of the cellular transcriptional response to RocA. Our functional assays suggest that RocA or similar translation inhibitors may show efficacy against ER− breast tumors and that the levels of MondoA and TXNIP should be considered when exploring these potential treatment options.
The Risk of Primary Uterine and Cervical Cancer After Hysteropexy.

OBJECTIVE The aim of the study was to determine the rate of subsequent uterine/cervical cancer after hysteropexy compared with hysterectomy with apical prolapse repair. METHODS The study used a retrospective cohort of women with uterovaginal prolapse using the Cerner Health Facts database between 2010 and 2018. We identified sacrospinous or uterosacral ligament suspensions or sacral colpopexy/hysteropexy and excluded those with previous hysterectomy. We used the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes for endometrial cancer/hyperplasia and cervical cancer and then reviewed each case, excluding those whose cancer existed at time of prolapse repair. Given that 0 cancer cases were identified, we used Wilson, Jeffreys, Agresti-Coull, Clopper-Pearson, and Rule of 3 to define 95% confidence intervals to estimate the highest possible rate of cancer in each cohort. RESULTS A total of 8,927 patients underwent apical prolapse surgery. Of 4,510 with uterovaginal prolapse, 755 (16.7%) underwent hysteropexy. Seventy one with hysterectomy and 5 with hysteropexy had codes for subsequent gynecologic cancer but were excluded on further review. This left 0 gynecologic cancer cases with the largest 95% confidence interval of 0%-0.61% for hysteropexy versus 0%-0.13% for hysterectomy (P > 0.05). The hysteropexy cohort was older (62.6 years vs 57.3 years, P < 0.0001), more likely to have public insurance (51.0% vs 37.9%, P < 0.0001), and less likely to smoke (4.5% vs 7.6%, P = 0.0026). Median follow-up was longer after hysteropexy (1,480 days vs 1,164 days, P < 0.0009). CONCLUSIONS We can say with 95% certainty that uterine or cervical cancer will develop after hysteropexy in fewer than 0.61% of women, which was not different if hysterectomy was performed. This should be included in preoperative counseling for hysteropexy. Studying longer follow-up after hysteropexy may capture more cases of subsequent cancer development.
The Impact of Family Relationships on School Bullies and Their Victims.

Stocker and Youngblade (1999) emphasize the importance of family relationships in helping children develop the skills necessary for positive peer interactions. They argue that because the family is where the child ﬁrst sees and experiences relationships, it is through the family that the child will learn what to expect in relationships, how to behave in relationships, and the interpersonal skills to be used in relationships. As seen in previous chapters, research indicates clear differences in the characteristics and behaviors of bullies (those who bully others), victims (those who are victimized by others), bully-victims (those who both bully and are victimized by others), and children not involved in bullying. Thus, it is likely that at least some of the characteristics that predispose children to becoming victims or bullies develop before the child enters school and that some of these characteristics are developed through experiences within the family. This chapter will examine the parents and siblings of children involved in bullying and will highlight several theories which explain the link between family characteristics and school bully involvement.
Early perceptions of COVID-19 intensity and anti-Asian prejudice among White Americans

Anecdotal reports suggested an uptick in anti-Asian prejudice corresponding with the initial outbreak of the COVID-19 pandemic. Examining responses from White U.S. citizens (N = 589) during the fir...
FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm.

Approximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. While the adverse prognostic impact of FLT3-ITDmut in AML has been clearly proven, the prognostic significance of FLT3-TKDmut remains speculative. Current guidelines recommend rapid molecular testing for FLT3mut at diagnosis and earlier incorporation of targeted agents to achieve deeper remissions and early consideration for allogeneic stem cell transplant (ASCT). Mounting evidence suggests that FLT3mut can emerge at any timepoint in the disease spectrum emphasizing the need for repetitive mutational testing not only at diagnosis but also at each relapse. The approval of multi-kinase FLT3 inhibitor (FLT3i) midostaurin with induction therapy for newly diagnosed FLT3mut AML, and a more specific, potent FLT3i, gilteritinib as monotherapy for relapsed/refractory (R/R) FLT3mut AML have improved outcomes in patients with FLT3mut AML. Nevertheless, the short duration of remission with single-agent FLT3i’s in R/R FLT3mut AML in the absence of ASCT, limited options in patients refractory to gilteritinib therapy, and diverse primary and secondary mechanisms of resistance to different FLT3i’s remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3mut AML.
An Emerging Area in Second Language Phonology: The Perception of English Vowels by Adult Second Language Learners

Although the field of second language acquisition (SLA) has largely advanced over the last few decades, the area of second language (L2) phonology has not been a focus of many studies. Major (1998) found that “of the nearly 200 articles published in Studies in SLA [from 1988 to 1998], only about a dozen focused on phonetics and phonology” (p. 131). Since then, the area has largely expanded, as discussed in Eckman (2004), evolving from studies that cited first language (L1) influence as a main explanation for L2 phonology to research that has turned to universal principles driven by Universal Grammar (UG). Several crosslinguistic speech perception models have been developed as well, and many empirical studies have been undertaken to yield support. One of the most fertile domains for the investigation of L2 phonology has been the syllable (Eckman, 2004, p. 527). However, most of the studies have concentrated on the onset or the coda, while there is much yet to be explored for the acquisition of the nucleus of the syllable – the vowel. This paper is a literature review of the emerging area of L2 phonology, focusing on the perception of English vowels by adult L2 learners.
Some observations of a sheared Rayleigh-Taylor/Benard instability

An account is provided of preliminary flow visualization observations made in an unstably stratified flow with shear superimposed. The structures observed appear to be the superposition of a Rayleigh-Taylor/Benard instability and a Kelvin-Helmholtz instability. Aside from its intrinsic fundamental value, the study of these structures is of special interest to theoreticians developing nonlinear stability calculation methodologies.
Some Practical Advice on the Interchangeability of Levothyroxine Products and Drug Product Selection

This article discusses Issues concerning levothyroxine bloequlvalence and Interchangeability and provides pharmacists and other health care professionals with some practical advice on the substitution of levothyroxine and other drug products.
Elections and Democracy: To Cheat or to Change?

The Forensics of Election Fraud: Russia and Ukraine. By Mikhail Myagkov, Peter C. Ordeshook, Dimitri Shakin. Cambridge: Cambridge University Press, 2009. 289 pp., $30.99 paperback (IBSN-13: 978-0-521-74836-0). The Politics of Electoral Reform: Changing the Rules of Democracy. By Alan Renwick. Cambridge: Cambridge University Press, 2010. 312 pp., $90.00 hardcover (IBSN-13: 978-0-521-76530-05). Cambridge University Press has released two monographs recently that deal with the complex relationship of elections and democracy. Though substantively distinct, these books both address a core concern regarding the ways political actors attempt to influence electoral outcomes and the consequences of such attempts for democracy. For Myagkov, Ordeshook, and Shakin, the question is: how can we detect election fraud where we suspect it has occurred? Renwick's questions center on the dynamics of electoral system reform. Both works bring an arguably under-utilized methodological approach to bear on their questions, and both provide empirical analysis of a small number of cases. As indicated by the title, The Forensics of Election Fraud , Myagkov et al. investigate election fraud in Russia and Ukraine, while Renwick's The Politics of Electoral Reform traces the process of electoral system reform in France, Japan, Italy, and New Zealand. Myagkov et al. attribute their motivation for Forensics to the work of one Dr. Alexander Sobyanin, a scholar committed to exposing electoral fraud in Russia. In many ways, the book maintains this tight focus throughout, though one can certainly imagine theoretical extensions and methodological applications. The authors’ fraud detection efforts focus very specifically on those illegal activities that directly distort election results: ballot box stuffing and the deliberate manipulation of vote counts. They introduce three forensic indicators of election fraud, based on the logic of what fraud-free elections should look like, in terms of turnout, candidate vote shares, and the relationship between the two. Deviations from any of these three expectations might indicate fraud. First, they argue that as turnout increases so should the votes for each candidate, at a rate proportional to their support in the electorate. Second, they argue that turnout should be normally distributed across districts, with small proportions of high and low turnout districts …
Amiodarone: Pharmacology and Antiarrhythmic and Adverse Effects

Amiodarone is a benzofuran derivative that has been effective for the treatment of both supraventricular and ventricular tachyarrhythmias. It has a large volume of distribution, moderate bioavailability and a long half-life. Its pharmacokinetics are not well understood and its tissue distribution is not typical of a 2-compartment model. Due to ocular, dermatologic, gastrointestinal, neurologic, cardiovascular, thyroid and pulmonary toxicity, amiodarone should be reserved for use in patients with refractory and/or life-threatening arrhythmias.
A Personal Constitution

This article argues that law schools should better prepare students to face the personal challenges of lawyering by emphasizing the central role that personal values play in making career decisions. It then explains how this goal can be achieved: through a required first-year course on professional satisfaction. Implementing a course that teaches law students how to approach the difficult professional decisions they must make in a manner that comports with their personal values would ameliorate the growing trend of lawyer dissatisfaction, producing happier law students, well-adjusted lawyers, and a more fruitful and impactful legal profession. To that end, this article provides a framework for teaching law students to make careers decisions based upon personal values: the personal constitution.
Developing Mathematics for Insight into Sensorimotor Neurobiology

This paper summarizes a research program to express the organization of sensorimotor control by specifying physiological states and the conditions for transitions among them. By a slight change in standard notation, conditional dynamics provides a moving spotlight, focussing on salient subspaces within a high-dimensional space. This mathematical approach serves as a window on the organization of sensorimotor neurobiology. The intertwined efforts to express the intrinsic organization of neurobiology and to clarify it mathematically are yielding a mathematical structure that is growing on fertile empirical ground.
Jastrow-Slater trial energy for the low density hard sphere fermi gas

The ability of a variational calculation with a Jastrow-Slater trial function to yield the leading terms in the ground state energy of a low density hard sphere fermi gas is discussed. A cluster expansion of the variational trial energy is developed which fully includes exchange processes between particles in the cluster and the other particles of the medium. The result, however, is that the spin-degeneracy of the Lee-Yang term is not recovered; this result was previously obtained with analyses in which the series of exchange terms was truncated.
Food Applications of Poly-Gamma-Glutamic Acid

Poly-γ-glutamic acid (γ-PGA) is a unique polymer in which both d- and l-glutamic acids are combined with γ-linkages. γ-PGA is safe, water soluble, anionic, and edible substance, which has many features such as high water absorbability, viscosity, metal-binding property, less susceptible for intestinal enzymes, and tasteless, etc. and the production of which has been already industrially established. Therefore, γ-PGA is highly attractive, promising food ingredient in the food industry. Several food applications using its physiological and physical properties modifying and taste perception modifying function have been demonstrated at present. However, the mechanism which γ-PGA demonstrates its functions and the relationships between the functions and its structural properties (molecular weight, d/l ratio, etc.) has not been understood. Detailed research in this area will be needed and clarity in this area will lead to develop more attractive applications of γ-PGA.
Utility of amniocentesis in afebrile women with preterm labor

Abstract Objectives: To determine 1) the rate of positive markers of intraamniotic infection (IAI) in women with preterm labor (PTL) undergoing amniocentesis (AMNIO), 2) the outcomes of pregnancies with positive markers of IAI, 3) whether management was altered based on results, and 4) the rate of rupture of membranes (ROM) following AMNIO. Study design: Our policy was to perform AMNIO on afebrile women with PTL if there was 1) no response to tocolysis, 2) maternal/fetal signs of IAI, or 3) advanced cervical dilation (> 3 cm, ACD), or if fetal lung maturity (FLM) needed to be checked. Cases were identified from 1998 to 1999 by ICD-9 codes. Cases were excluded for fever or ROM before AMNIO. Results: Of the 65 women who were included, 63% received antibiotics before the AMNIO. The mean gestational age (GA) at AMNIO was 33.1 weks, and the mean GA at delivery was 34.1 weeks. The primary indications for AMNIO were FLM (52%), no response to tocolysis (26%), maternal signs (18%), and ACD (1.5%). There were 2 positive cultures (3%), 2 positive Gram stains (3%), 8 patients with white blood cell count of more than 50/uL (12%), 13 patients with glucose less than 15 (20%), and 24 patients with glucose less than 20 (37%). Only glucose less than 15 was associated with positive cultures (P = 0.04). No positive marker of IAI was associated with abruption, meconium, clinical chorioamnionitis, respiratory distress syndrome, or sepsis. Management was changed based on AMNIO results in 25 cases (39%). ROM followed AMNIO in 14% (mean 1.7 days, maximum 4 days). If ROM occurred, 66% delivered within 48 hours. Conclusions: The rate of IAI was low, and no marker of IAI was associated with neonatal morbidity. These findings may be a result of our use of antibiotics before AMNIO, our culture technique, or changes in obstetric management based on our findings. The 14% risk of ROM was higher than expected. The role of AMNIO in PTL is unclear. A randomized controlled trial is needed to address efficacy and safety of AMNIO in PTL in afebrile women.
Haptotropic rearrangement in tricarbonylchromium complexes of 2-aminobiphenyl and 4-aminobiphenyl

The para-aminobiphenyl compound [(η6-C6H5)(C6H4-4-NH2)]Cr(CO)3 (1) has an arene–phenyl dihedral angle of 38.01(6)°, as determined by single-crystal X-ray crystallography, and 34.7(11)°, as determined by DFT calculations. It undergoes haptotropic rearrangement at 140 °C in solution to form [(η6-C6H4-4-NH2)(C6H5)]Cr(CO)3 (2), even though previous reports have suggested that such rearrangements should not be observed in compounds with arene–phenyl dihedral angles greater than 22°. NMR analysis gave a rate constant of k = 5.0 × 10−5 s−1 for the rearrangement of 1 to 2. The ortho-substituted analog [(η6-C6H5)(C6H4-2-NH2)]Cr(CO)3 (3) has an arene–phenyl dihedral angle of 67.70(7)°, as determined by single-crystal X-ray crystallography, and 51.9(10)°, as determined by DFT calculations. Surprisingly, even though it displays a more extreme canting of arene rings, 3 rearranges to [(η6-C6H4-2-NH2)(C6H5)]Cr(CO)3 (4) at 140 °C in solution with a rate constant of k = 2.6 × 10−4 s−1. This approximately five-fold rate enhancement likely results from the ortho-amino group providing intramolecular stabilization for intermediates formed during the rearrangement.