cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of ethanol-administration on hepatic ethanol and drug-metabolizing enzymes and on rates of ethanol degradation.

Abstract Ethanol administration was recently shown to enhance the activities of microsomal enzyme systems which metabolize ethanol and other drugs. The present study was designed to establish the time sequence and the mechanism that may account for the increases in enzyme levels, and to determine whether the increases in microsomal ethanol-oxidizing activity are accompanied by comparable changes in the rates of ethanol degradation in vivo. Male rats were fed ethanol for periods of 24, 48, and 72 hours, 7, and 14 days. Whereas liver weights and the cytosol enzymes alcohol dehydrogenase and lactate dehydrogenase were not changed, significant increases were obtained as early as 24 hours after ethanol administration for microsomal ethanol-oxidizing activity and at 48 hours for aniline hydroxylase and cytochrome P-450. Microsomal protein concentration was increased only at 14 days. Protein turnover studies demonstrated no changes in the rate of incorporation of 1- 14 C-l-leucine into microsomal protein, but significant decreases in the rate of degradation of 1- 14 C-l-leucine from microsomal protein were found at 14 days. The rates of ethanol disappearance from the blood were increased; however, the calculated mean increase of the microsomal ethanol-oxidizing activity accounted for only 13.8 per cent of the mean increase in the rate of in vivo ethanol disappearance at 7 days. The findings suggest that the mechanism of induction by ethanol is different from that of other known inducers, and that in vivo factors beside the absolute increase in microsomal enzyme activity must account for the observed changes in the rates of ethanol degradation.
The effects of triethylene melamine and related compounds on the leukocytes of mouse leukemia.

1. In the usual therapeutic dosage in mice with the Ak4 strain of leukemia, TEM caused a prolongation of survival time, held the total leukocyte count down at severely leukopenic levels, delayed the appearance of immature lymphocytes in the peripheral blood, and caused a marked delay in the appearance of leukemic infiltrations of the liver, spleen, bone marrow and kidney. 2. A single massive dose of TEM, administered on the seventh day of the disease when the total leukocyte count was high, caused a rapid fall in the count and depressed the number of prolymphocytes in the peripheral blood. 3. Single massive doses of such structurally related compounds as hexamethylene diethylenurea, 2,4-diethylenimino-6-amino- s -triazine, and to a lesser degree, 2-ethylenimino-4,6-dimethoxy- s -triazine caused a similar fall in the total leukocyte count when administered on the seventh day of the disease.
Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells

Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis plays an important role in translating TCR signal strength into proportional activation of enhancers and genes essential for T cell function.
Dynamic Approximation with Feedback Control for Energy-Efficient Recurrent Neural Network Hardware

This paper presents methodology of feedback-controlled dynamic approximation to enable energy-accuracy trade-off in digital recurrent neural network (RNN). A low-power digital RNN engine is presented that employs the proposed dynamic approximation. The on-chip feedback controller is realized by utilizing hysteretic or proportional controller. The dynamic adaptation of bit-precisions during the RNN computation is selected as approximation approach. Considering various applications, the digital RNN engine designed in 28nm CMOS shows ~36% average energy saving compared to the baseline case, with only ~4% of accuracy degradation on average.
1991: Some Financial Perspectives on Comparative Costs of Capital

Much has been written on whether firms in some countries have a lower cost of capital than firms in other countries. This chapter first reviews the cost of capital measurement methodologies employed in prior studies of financially derived competitive advantage (FDCA). The problems with these studies motivate use of an alternative methodology based on widely accepted models of asset pricing in the literature of financial economics.1
Test technology of UHV AC bushing and its application

For the urgent needs of the bushing test technology and inspection method with the rapid development of UHV transmission project, based on the technical requirements of the UHV transformer bushing and use for reference on the existing transformer bushing test technology, a complete set of UHV transformer bushing test system including insulation test, thermal rise test has been established, and also the relevant test methods has been proposed. The test technology proposed in this paper has been applied to the UHV transformer bushing used in the UHV power transmission engineering, meanwhile the validity of the test system and technology has been verified.
Treatment targeted at underlying disease versus palliative care in terminally ill patients: a systematic review.

Objective To assess the efficacy of active treatment targeted at underlying disease (TTD)/potentially curative treatments versus palliative care (PC) in improving overall survival (OS) in terminally ill patients. Design We performed a systematic review and meta-analysis of randomised controlled trials (RCT). Methodological quality of included RCTs was assessed using the Cochrane risk of bias tool. Data sources Medline and Cochrane databases were searched, with no language restriction, from inception to 19 October 2016. Eligibility criteria for selecting studies Any RCT assessing the efficacy of any active TTD versus PC in adult patients with terminal illness with a prognosis of Results Initial search identified 8252 citations of which 10 RCTs (15 comparisons, 1549 patients) met inclusion criteria. All RCTs included patients with cancer. OS was reported in 7 RCTs (8 comparisons, 1158 patients). The pooled results showed no statistically significant difference in OS between TTD and PC (HR (95% CI) 0.85 (0.71 to 1.02)). The heterogeneity between pooled studies was high (I 2 =62.1%). Overall rates of adverse events were higher in the TTD arm. Conclusions Our systematic review of available RCTs in patients with terminal illness due to cancer shows that TTD compared with PC did not demonstrably impact OS and is associated with increased toxicity. The results provide assurance to physicians, patients and family that the patients9 survival will not be compromised by referral to hospice with focus on PC.
Evaluation of MJO Predictive Skill in Multiphysics and Multimodel Global Ensembles

AbstractMonthlong hindcasts of the Madden–Julian oscillation (MJO) from the atmospheric Flow-following Icosahedral Model coupled with an icosahedral-grid version of the Hybrid Coordinate Ocean Model (FIM-iHYCOM), and from the coupled Climate Forecast System, version 2 (CFSv2), are evaluated over the 12-yr period 1999–2010. Two sets of FIM-iHYCOM hindcasts are run to test the impact of using Grell–Freitas (FIM-CGF) versus simplified Arakawa–Schubert (FIM-SAS) deep convection parameterizations. Each hindcast set consists of four time-lagged ensemble members initialized weekly every 6 h from 1200 UTC Tuesday to 0600 UTC Wednesday.The ensemble means of FIM-CGF, FIM-SAS, and CFSv2 produce skillful forecasts of a variant of the Real-time Multivariate MJO (RMM) index out to 19, 17, and 17 days, respectively; this is consistent with FIM-CGF having the lowest root-mean-square errors (RMSEs) for zonal winds at both 850 and 200 hPa. FIM-CGF and CFSv2 exhibit similar RMSEs in RMM, and their multimodel ensemble mean e...
Fuzzy-based approaches to human computation for military situational awareness

The objective of this paper is to motivate human computation research, leveraged with the advantages of fuzzy-based systems, within the military situational awareness domain. The goal is to stimulate the use of fuzzy logic's ability for providing more intuitive ways to model complex systems as the basis for research aimed toward facilitating human computation in the context of improving military situational awareness.
The Importance of Human Information Processing: A Behavioral Economics Model for Predicting Domain Name Choice

Studying the decisions of 25,646 domain name registrants reveals that behavioral economics models more accurately predict name choice than models based on expected utility theory. These findings have implications for Internet governance, and organizations that measure similarity and competition in domain name registration.
The Truesdell Method

Truesdell’s study of the functional equation $$ \frac{\partial }{{{\partial_{{\rm Z}}}}}\,F\left( {z,\alpha } \right) = F\left( {z,\,\alpha + 1} \right), $$ called the F-equation, yielded many valuable results, among which is his method for obtaining generating functions. By this method Truesdell [1] obtained both ascending and descending generating functions. For example, if the elements of a given set of functions \( \left\{ {{\phi_n}(x)} \right\} \) satisfy a differential-difference equation of the ascending type, $$ \phi_n^{'}\,(x) = A\left( {x,\,n} \right)\,{\phi_n}\,(x) + B\left( {x,\,n} \right)\,{\phi_{{n + 1}}}\,(x), $$ with coefficients A(x, n) and B(x, n) suitably restricted, then a generating function can be found for the set \( \left\{ {{\phi_{{k + n}}}\,(x)} \right\}, \), where k is fixed. Furthermore, if the elements of the set satisfy a differential-difference equation of the descending type, $$ \phi_n^{'}\,(x) = C\left( {x,\,n} \right)\,{\phi_n}\,(x) + D\left( {x,\,n} \right)\,{\phi_{{n - 1}}}\,(x), $$ with coefficients suitably restricted, a generating function can be found for the set \( \left\{ {{\phi_{{k - n}}}\,(x)} \right\}, \), when k is fixed.
“Isn’t It Just Bullshit?”: From Uncreative Writing to Warhol and Back

That some radical claims for Uncreative Writing prove to be inaccurate does not mean that the work is essentially conservative. Looking at Uncreative Writing’s inheritance from the Andy Warhol of the Silver Factory years—his laconic problematizing of the artist’s relationship to his object matter—Chapter 3 engages close readings of Vanessa Place, Robert Fitterman and Ara Shirinyan to show that at its most uncomfortable, Uncreative Writing offers a telling critique of the cultural privilege on which avant-garde literature rests.
Distributed algorithms for the average bridge consensus

By considering the existence of bridge sensor nodes that lose the capability of sensing, the average bridge consensus problem aims to achieve the average of selective observations only from sensing nodes while bridge nodes play the role of relaying information. We note that traditional average consensus algorithms achieve the global average of states from all nodes in the network, which are not directly applied here. In this paper we present two distributed algorithms for solving the bridge consensus problem on fixed-tree networks in finite time and a class of time-varying networks exponentially fast, respectively. Both theoretical and numerical results are provided for validations of the proposed algorithms.
LY2087101 and dFBr share transmembrane binding sites in the (α4)3(β2)2 Nicotinic Acetylcholine Receptor.

Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChRs) have potential therapeutic application in neuropathologies associated with decrease in function or loss of nAChRs. In this study, we characterize the pharmacological interactions of the nAChRs PAM, LY2087101, with the α4β2 nAChR using mutational and computational analyses. LY2087101 potentiated ACh-induced currents of low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs with similar potencies albeit to a different maximum potentiation (potentiation I max = ~840 and 450%, respectively). Amino acid substitutions within the α4 subunit transmembrane domain [e.g. α4Leu256 and α4Leu260 within the transmembrane helix 1 (TM1); α4Phe316 within the TM3; and α4Gly613 within TM4] significantly reduced LY2087101 potentiation of (α4)3(β2)2 nAChR. The locations of these amino acid residues and LY2087101 computational docking analyses identify two LY2087101 binding sites: an intrasubunit binding site within the transmembrane helix bundle of α4 subunit at the level of α4Leu260/α4Phe316 and intersubunit binding site at the α4:α4 subunit interface at the level of α4Leu256/α4Ile315 with both sites extending toward the extracellular end of the transmembrane domain. We also show that desformylflustrabromine (dFBr) binds to these two sites identified for LY2087101. These results provide structural information that are pertinent to structure-based design of nAChR allosteric modulators.
Patient and Family Advisory Councils (PFACs): Identifying Challenges and Solutions to Support Engagement in Research.

The aim was to describe barriers to patient and family advisory council (PFAC) member engagement in research and strategies to support engagement in this context. We formed a study team comprising patient advisors, researchers, physicians, and nurses. We then undertook a qualitative study using focus groups and interviews. We invited PFAC members, PFAC leaders, hospital leaders, and researchers from nine academic medical centers that are part of a hospital medicine research network to participate. All participants were asked a standard set of questions exploring the study question. We used content analysis to analyze data. Eighty PFAC members and other stakeholders (45 patient/caregiver members of PFACs, 12 PFAC leaders, 12 hospital leaders, 11 researchers) participated in eight focus and 19 individual interviews. We identified ten barriers to PFAC member engagement in research. Codes were organized into three categories: (1) individual PFAC member reluctance; (2) lack of skills and training; and (3) problems connecting with the right person at the right time. We identified ten strategies to support engagement. These were organized into four categories: (1) creating an environment where the PFAC members are making a genuine and unique contribution; (2) building community between PFAC members and researchers; (3) best practice activities for researchers to facilitate engagement; and (4) tools and training. Barriers to engaging PFAC members in research include patients’ negative perceptions of research and researchers’ lack of training. Building community between PFAC members and researchers is a foundation for partnerships. There are shared training opportunities for PFAC members and researchers to build skills about research and research engagement.
The ABC of MOOCs: Affect and its inter-play with behavior and cognition

We report on a study of affective states of learners in a Massive Open Online Course (MOOC) and the interplay of Affect, Behavior and Cognition at various stages of the course. Affect is measured through a series of self-reports from learners at strategic time posts during the period of study. Behavior is characterized in terms of a learners' engagement, interactivity, impatience and reflectivity, which constitute a set of novel high-level features derived from the clickstream of learner interactions. Cognition is evaluated from the performance of learners on assessments that are part of the course. We discover that learners in the MOOC experience multiple as well as mixed emotions as they go through the course, which we handle using the psychological dimensions of arousal and valence. This results in a set of emotional quadrants, whose co-occurrence analysis reveals a strong association with cognition and specific behavioral characteristics demonstrated by the learner. These results advance our understanding of the experience of MOOC learners to a more holistic level across the key dimensions of affect, behavior and cognition. They also have important implications for the design of the next generation MOOCs that can potentially leverage affect and behavior-aware interventions to drive greater personalization and eventually, improved learning outcomes.
Non-determinism Reduces Construction Time in Active Self-assembly Using an Insertion Primitive

We consider efficient construction of DNA-based polymers in a model introduced by Dabby and Chen (SODA 2013) called insertion systems, where monomers insert themselves into the middle of a growing linear polymer. Specifically, we describe a new family of non-deterministic insertion systems that construct length-n polymers in \(\varTheta (\log ^{3/2}(n))\) expected time, breaking the lower bound of \(\varOmega (\log ^{5/3}(n))\) for deterministic construction. We also prove that this time is optimal for systems constructing finite polymers, and that the \(\varTheta (\log (n))\) monomer types used in the construction is optimal for this time.
ON THE IRREDUCIBLE CHARACTERS OF A SIMPLE GROUP OF ORDER 241·313·56·72·11·13·17·19·23·31·47

Recently Fischer produced evidence for the existence of a simple group F 2 of order 2 41 . 3 13 . 5 6 .7 2 .11.13.17.19.23.31.47. The group F 2 would be generated by a class of involutions, any two of whose members have product of order at most four. If d is an involution in this class, CF 2 (d) ≅ Z 2 \ 2 E 6 (2)\ Z 2 . As of this date, the existence and uniqueness of F 2 remains unproven. The chapter presents the assumption that such a group does exist and presents several results on its complex irreducible characters.
Developing a Life Skills Evaluation Tool for Assessing Children Ages 9-12

Efforts that attend to the developmental needs of children, enhance their capacity to learn, and support their potential for becoming successful, have tremendous merit. Therefore, it is critical that steps are taken to evaluate the effectiveness of such endeavors. The purpose of this study was to create and validate a life skill outcomes instrument for use in extension youth programs. This instrument validation study utilized both quantitative and qualitative methodologies to establish the validity and reliability of a life skills instrument for nine to twelve year olds. The data collected from 111 participants suggests that the instrument is both valid and reliable for the intended age group. Study results, limitations, and ideas for future research are discussed.
Diffuse anterior retinoblastoma

Das Retinoblastom ist der haufigste intraokulare Tumor im Kindesalter. Das diffuse anteriore Retinoblastom ist eine sehr seltene Manifestationsform dieses Tumors und tritt normalerweise bei vergleichsweise alteren Kindern auf. Charakteristischerweise zeigt sich eine massive Infiltration des vorderen Augenabschnitts mit Tumorzellen, die sich klinisch als anteriore Uveitis mit Pseudohypopyon darstellen kann – der eigentliche retinale Fokus ist bisweilen so klein, dass er ubersehen werden kann. Dieser Fallbericht beschreibt die klinischen und histologischen Befunde eines diffusen anterioren Retinoblastoms.
Evaluation of Fungicides and Herbicides for Management of White Mold of Soybean

Materials and Methods Asgrow 3231 was planted on May 12, 2011. Fungicides were either applied at growth stage R1 (July 13) or R3 (July 26). Disease was assessed on August 23 when soybeans were at growth stage R6. Harvest was completed on October 14. Moisture was measured and yields were adjusted to 13 percent moisture. Very little to no white mold was observed in every treatment. The experiment was located in a field equipped with center pivot irrigation and received regular irrigation to keep the lower canopy moist and conducive to formation of white mold infection. However, unseasonably warm weather during July and early August provided poor conditions for white mold development.
Studies of oogenesis in the rotifer, Asplanchna. I. Fine structure of the female reproductive system.

Oocyte development in Asplanchna brightwelli was studied by observation through the transparent body wall of living females and by electron microscopy. During oogenesis, which requires four to six hours, the oocyte increases in volume approximately 1000-fold. Most of its cytoplasm appears to be derived from the vitellarium by direct flow through the cytoplasmic bridge. This flow is rapid enough to be easily observed in the living female at low magnifications. Ribosomes, mitochondria, cortical granules, and lipid droplets were observed in the bridge area in electron micrographs.
Heart Rate Fragmentation as a Novel Biomarker of Adverse Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis

Background: A major objective of precision medicine is the elucidation of non-invasive biomarkers of cardiovascular (CV) risk. Recently, we introduced a new dynamical marker of sino-atrial instability, termed heart rate fragmentation (HRF), which outperformed traditional and nonlinear heart rate variability metrics in separating ostensibly healthy subjects from patients with coronary artery disease. Accordingly, we hypothesized that HRF may be a dynamical biomarker of adverse cardiovascular events (CVEs). Methods: This study employed data from a cohort of participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of sub-clinical heart disease. Interbeat interval time series (n = 1963), derived from the electrocardiographic channel of the polysomnogram study, were analyzed using the newly introduced metrics of fragmentation, as well as traditional heart rate variability (HRV) indices and the short-term detrended fluctuation analysis exponent. Cox regression analysis was used to assess the association between HR dynamic indices and CV outcomes in unadjusted and adjusted models. Results: The mean (± SD) follow-up time was 2.97 ± 0.63 years. In adjusted models, higher fragmentation was significantly associated with incident CVEs (number of events; hazard ratio [95% confidence interval]: n = 72, 1.43 [1.16-1.76]) and CV death (n = 21; 1.65 [1.15-2.36]). The traditional HRV and the fractal indices were not associated with CVEs or CV death. The most discriminatory fragmentation indices added significant value to Framingham and MESA CV risk indices in all analyses. Conclusion: Our findings show that HRF has promise as a non-invasive, automatable biomarker of CV risk. The basic mechanisms underlying fragmentation remain to be delineated. Its association with incident outcomes raises the possibility of connections to degenerative changes in the multisystem network controlling SAN function.
Future research directions for prevention and treatment of obstetric venous thromboembolism

Pregnant patients are at high risk for venous thromboembolism, which accounts for 9% of maternal deaths in the United States. However, there are still a number of unanswered questions with regards to prevention, diagnosis, and treatment of this condition. This article highlights areas for future research with regards to three questions pertaining to venous thromboembolism in pregnancy: 1) how can risk stratification be improved; 2) what are the most effective means of prevention; 3) what is the role of novel oral anticoagulants in pregnancy and the postpartum period?
Associations between e-cigarette and combustible cigarette use among U.S. cancer survivors: implications for research and practice.

Prior studies established significant associations between e-cigarette use and combustible cigarette smoking in the general population; however, little is known about such associations among cancer survivors. Thus, the current study examined possible associations between e-cigarette use and combustible cigarette smoking among U.S. cancer survivors. Cross-sectional data were drawn from the 2016 Behavioral Risk Factor Surveillance System Survey. Binary logistic regression was used to analyze the associations between e-cigarette user status and combustible cigarette-smoking status in a sample of 4680 cancer survivors, controlling for alcohol use and sociodemographic factors. Analyses were weighted for unequal probability of sample selection to reflect national cancer survivor population estimates. Prevalence for current e-cigarette use and combustible cigarette smoking for cancer survivors was 2.57% and 16.16%, respectively. In the adjusted analyses, cancer survivors who reported current e-cigarette use, compared to never-users, had greater odds of being current combustible cigarette smokers (odds ratio [OR] = 11.81, 95% confidence interval [CI] = 5.38–25.93). Likewise, former e-cigarette users, compared to never-users, had greater odds of being current combustible cigarette smokers (OR = 15.90, 95% CI = 10.68–23.36). Among cancer survivors in the USA, e-cigarette use had a positive and highly significant association with combustible cigarette smoking. In order to prevent multiple and substitute use of nicotine-delivery products, prevention interventions and cessation programs designed for cancer survivors should specifically target both current combustible cigarette smokers and non-smokers who report former and current e-cigarette use.
Assessing the Learning Needs of Pediatric Emergency Medicine Fellows Related to Child Poverty and Social Determinants of Health: a Curricular Needs Assessment Study

Background: Twenty-one percent of U.S. children live in poverty. Population-based studies indicate an association between poverty and higher emergency department (ED) utilization rates. Given that EDs serve as continuous points of access within our nation’s health care system--for social as well as medical emergencies—providers must be well-equipped to understand and meet the specific needs of children living in poverty and to effectively address their social determinants of health (SDH) in the ED setting. The Accreditation Council on Graduate Medical Education (ACGME) does not specify requirements for training related to child poverty or SDH in PEM fellowships; currently, there is no “standard” curriculum focused on …
qDRIP: Quantitative differential RNA:DNA hybrid immunoprecipitation sequencing

Abstract R-loops are dynamic, co-transcriptional nucleic acid structures that facilitate physiological processes and cause DNA damage in certain contexts. Perturbations of transcription or R-loop resolution are expected to change their genomic distribution. Next-generation sequencing approaches to map RNA:DNA hybrids, a component of R-loops, have so far not allowed quantitative comparisons between such conditions. Here we describe quantitative differential RNA:DNA immunoprecipitation (qDRIP), a method combining synthetic RNA:DNA-hybrid internal standards with high-resolution, strand-specific sequencing. We show that qDRIP avoids biases inherent to read-count normalization by accurately profiling signal in regions unaffected by transcription inhibition in human cells, and by facilitating accurate differential peak calling between conditions. Finally, we use these quantitative comparisons to make the first estimates of the absolute count of RNA:DNA hybrids per cell and their half-lives genome-wide. Overall, qDRIP allows for accurate normalization in conditions where R-loops are perturbed and for quantitative measurements that provide previously unattainable biological insights.
A Novel Probe for Spliceosomal Proteins that Induces Autophagy and Death of Melanoma Cells Reveals New Targets for Melanoma Drug Discovery.

Background/aims Despite recent advances in melanoma drug discovery, the average overall survival of patients with late stage metastatic melanoma is approximately 3 years, suggesting a need for approaches that identify new melanoma targets. We have previously reported a discovery of novel anti-melanoma compound 2155-14 (Onwuha-Ekpete et al., J Med Chem. 2014 Feb 27; 57(4):1599-608). In the report presented herein we aim to identify its target(s) and mechanism of action. Methods We utilized biotinylated analog of 2155-14 to pull down its targets from melanoma cells. Proteomics in combination with western blot were used to identify the targets. Mechanism of action of 2155-14 was determined using flow cytometry, RT-PCR, microscopy, western blot, and enzymatic activity assays. Where applicable, one-way analysis of variance (ANOVA) was used followed by Dunnett post hoc test. Results In the present study, we identified ATP-dependent RNA helicase DDX1 and heterogeneous nuclear ribonucleoproteins (hnRNPs) H1, H2 and A2/B1 as targets of anti-melanoma compound 215514. To the best of our knowledge, this is a first report suggesting that these proteins could be targeted for melanoma therapy. Mechanistic investigations showed that 2155-14 induces ER stress leading to potentiation of basal autophagy resulting in melanoma cell death in BRAF and NRAS mutated melanoma cells. Conclusion Identification of mode of action of 2155-14 may provide insight into novel therapies against a broad range of melanoma subtypes. These studies were enabled by the novel probe derived from a mixture-based library, an important class of chemical biology tools for discovering novel targets.
U-Pick Farms: Harvesting More than Pumpkins

Recreational experiences offer many benefits to individuals and society, including improved mental and physical health. Yet, limited evidence is available on the potential benefits of recreation as a path to stimulate desired behavioral outcomes. The purpose of this work is to discuss preliminary findings of whether participating in agritourism influences intended local foods purchasing behavior. To achieve this purpose, we surveyed 173 recreationists before and after visiting a farm offering recreational activities (agritourism) in 2018. Results of repeated measures multivariate analysis of variance indicate that agritourism influenced participants’ attitudes and intended behavior toward local foods although subjective norms and perceived behavioral control remained unchanged. However, the regression analysis indicated that changes in subjective norms and perceived behavioral control predicted changes in intended behavior. We conclude that agritourism can encourage consumers’ purchasing intentions of local foods, supporting an underexplored additional benefit of recreational experiences as a path to promote desirable behaviors. Further, agritourism experiences may be most effective at encouraging local foods purchasing when they show that buying local foods is socially supported and relatively easy. Subscribe to JPRA
Islet O-GlcNAcylation Is Required for Lipid Potentiation of Insulin Secretion through SERCA2.

Summary During early obesity, pancreatic β cells compensate for increased metabolic demand through a transient phase of insulin hypersecretion that stabilizes blood glucose and forestalls diabetic progression. We find evidence that β cell O-GlcNAcylation, a nutrient-responsive post-translational protein modification regulated by O-GlcNAc transferase (OGT), is critical for coupling hyperlipidemia to β cell functional adaptation during this compensatory prediabetic phase. In mice, islet O-GlcNAcylation rises and falls in tandem with the timeline of secretory potentiation during high-fat feeding while genetic models of β-cell-specific OGT loss abolish hyperinsulinemic responses to lipids, in vivo and in vitro. We identify the endoplasmic reticulum (ER) Ca2+ ATPase SERCA2 as a β cell O-GlcNAcylated protein in mice and humans that is able to rescue palmitate-stimulated insulin secretion through pharmacological activation. This study reveals an important physiological role for β cell O-GlcNAcylation in sensing and responding to obesity, with therapeutic implications for managing the relationship between type 2 diabetes and its most common risk factor.
Larval movement and survival of Helicoverpa zea (Boddie) in seed blends of non-Bt and Bt maize containing Agrisure Viptera® trait: Implications for resistance management

Abstract A seed blend refuge has been used to host susceptible insects for Bt maize insect resistance management (IRM) in the U.S. Maize Belt. One major concern in the use of seed blends is that larval movement among non-Bt and Bt plants could cause additional mortalities of susceptible insects. To address this concern, three caged-field trials were conducted to evaluate larval movement and survival of the corn earworm, Helicoverpa zea (Boddie), in eight seed blends of Cry1Ab/Vip3A maize with 0–30% non-Bt refuges. Each plot consisted of five rows and 21 plants in each row. Each plot was infested on the ear silks of the central plant at R1 stage with 35 F1 neonates produced from field-collected H. zea. After 9–13 d, no live larvae or kernel damages were observed on all Bt plants across all planting patterns and trials. In pure non-Bt plantings, 64.8% of the total larvae recovered moved away from the infested ears and survived on other plants, but most of the recovered larvae (86.8%) were located within a distance of three plants from the originally infested plants, and all live larvae were found on the originally infested or its adjacent rows. Larval survival and distribution were similar among seed blends with non-Bt plants in the centers of the plots, in which larvae predominantly located on the central plants (85.7% of the total recovered) with 100% being found on the central rows. Overall, larval recovery from central non-Bt plants in seed blends was 27.5% less than that from the pure non-Bt plantings. Kernel damage levels followed similar patterns as the number of larvae recovered in the plants, and larvae recovered developed similarly across treatments. Results of the study should have value in understanding the larval movement behavior of H. zea, assessing resistance evolution risk, and refining Bt maize IRM modeling for managing this pest. Additional studies are needed to determine the extent to which the reduction of refuge populations in seed blends influences resistance development of the pest to the Bt maize.
Cardiac Neuroanatomy for the Cardiac Electrophysiologist

The cardiac neuraxis is integral to cardiac physiology, and its dysregulation is implicated in cardiovascular disease. Neuromodulatory therapies are being developed that target the cardiac autonomic nervous system (ANS) to treat cardiac pathophysiology. An appreciation of the cardiac neuroanatomy is a prerequisite for development of such targeted therapies. Here, we provide a review of the current understanding of the cardiac ANS. The parasympathetic and sympathetic nervous system are composed of higher order cortical centers, brainstem, spinal cord, intrathoracic extracardiac ganglia and intrinsic cardiac ganglia. A series of interacting feedback loops mediates reflex pathways to exert control over the cardiac conduction system and contractile tissue. Further exploration of this complex regulatory system promises to yield neuroscience-based therapeutics for cardiac disease.
Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source.

Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer (“shuttle”) of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs.
MEC Standards on Edge Services

In the previous chapter, we have described the MEC platform, and the procedures related to the communication with MEC applications. It was also explained (as anticipated already in Chap. 1) that a MEC application can both consume services available in the MEC system and also produce services, which are made available by the MEC platform to other applications.
Food insecurity, morbidity, and susto: Factors associated with depression severity in Guatemala measured with the Personal Health Questionnaire 9.

Background:Depression is the largest contributor to non-fatal health loss globally and the majority of this burden occurs in low- and middle-income countries. Yet, estimates of prevalence rates and...
The Folding Pathway of Apomyoglobin

The detailed molecular mechanism of protein folding is currently a subject of intense interest. It is generally accepted that folding proceeds via the formation of intermediate species rather than through a random conformational search (1) However, the highly cooperative nature of the folding transition for most small proteins precludes structural characterization of intermediate species under equilibrium conditions. Spectroscopic studies of peptide fragments of proteins at equilibrium have been used to help identify regions of a protein with a high propensity to form structure in solution, and thus possible folding initiation sites (2). Kinetic studies of folding reactions have demonstrated the appearance of transient intermediates, but the lifetimes of these species are usually not compatible with detailed structural studies. Nonetheless, stopped-flow studies have provided valuable insights into the formation of folding intermediates. The development of pulsed amide proton exchange experiments in combination with two-dimensional (2D) NMR methods has facilitated the acquisition of detailed structural information on transiently populated folding intermediates (3–10) and has provided considerable impetus to the elucidation of protein folding pathways and the generalized mechanism of protein folding.
CMS calorimeter trigger circuits

The CMS level 1 trigger decision is based in part upon local information from the level 1 calorimeter trigger about the presence of objects such as photons, electrons and jets, as well as global sums of E/sub t/ and missing E/sub t/ (to find neutrinos). The electron/photon trigger is based on the recognition of a large and isolated energy deposit in the electromagnetic calorimeter by asking for a small hadronic energy deposited in the HCAL in the cluster region. We present a description of the calorimeter regional trigger crates, the receiver card, the electron isolation card and the jet summary card.
Business Process Representations Used in Redesign Projects Should Focus on Communication Flows

This paper reports on a quasi-experimental field study in which business process redesign groups in four different US organizations used two different types of business process representation. One of the representation types emphasized an activity flow (or workflow) view of business processes, which appears to currently be the most prevalent in actual operational-level business process redesign projects; the other emphasized a communication flow view. The study suggests that, contrary to assumptions likely underlying most of the current business process redesign practice, communication flow-oriented representations of business processes are perceived by those involved in their redesign as significantly more useful in the identification of opportunities for process improvement, more useful in the application of process redesign guidelines, more useful in the visualization of process changes, and more useful in the development of generic information technology solutions to implement new business processes, than activity flow-oriented representations. Important implications for managers and researchers stemming from these results are discussed.
Negotiating Puerto Rican Identity in Central Florida and Online

Resumen en: This article considers my work as a Central Florida folklorist and digital media scholar with Lilly Carrasquillo, a Central Florida artist from Puerto Ri...
The Effects of Bromocriptine Treatment During Early Pregnancy on Postpartum Maternal Behaviors in Rats

Prolactin, a hormone of the anterior pituitary, is involved in initiating maternal behavior, alleviating postpartum anxiety, and stimulating lactogenesis. Bromocriptine, a dopamine D2 receptor agonist, inhibits prolactin secretion. Bromocriptine administration represses postpartum maternal behaviors (pup retrieval) in mice, and causes elevated anxiety in the elevated plus maze [Larsen & Grattan (2010). Endocrinology 151(8): 3805–3814]. Whether similar effects exist in other species is unknown. The present study examined the possible involvement of prolactin during early gestation on maternal behavior and anxiety in rats. Bromocriptine given on days 2–4 of pregnancy resulted in impaired postpartum maternal behaviors in a novel environment during early lactation. However, compared to controls, bromocriptine-treated subjects did not exhibit increased postpartum anxiety in the elevated plus maze. These findings support work in mice that bromocriptine treatment during early gestation impedes postpartum maternal care, and indicate that early gestational hormonal status affects postpartum behavior more broadly in other mammals. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 56: 1431–1437, 2014.
Equations of motion of constrained mechanical systems: given force depends on constraint force

Abstract In the Lagrangean mechanics framework, forces are divided into given and constraint forces. Certain given forces may arise, however, only due to the constraint forces. In other words, they are coupled. The most well known example is that friction forces are due to normal forces. The standard procedure of using the Lagrange’s form of d’Alembert’s principle does not identify these forces directly. By using second order constraints, we propose two methods to determine these forces.
Keratinocyte-Derived Monocyte Chemoattractant Protein 1 (MCP-1): Analysis in a Transgenic Model Demonstrates MCP-1 Can Recruit Dendritic and Langerhans Cells to Skin

Chemokines are thought to play a central role in the recruitment and activation of leukocytes during inflammatory responses. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine of the C-C or β family that is chemotactic in vitro for monocytes, T cells, and basophils. Its excessive production by keratinocytes has been implicated in psoriasis and other skin diseases. To test the in vivo role of MCP-1 in inflammatory skin disease, we undertook the generation of transgenic mice that express murine MCP-1 in the basal layer of epidermis. Despite production of high levels of functional MCP-1 by basal keratinocytes, documented in vivo and in vitro , these mice did not exhibit spontaneous cutaneous inflammation or any other discernible skin pathology. In contrast, elicited inflammation in the skin of these mice differed qualitatively and quantitatively from that observed in non-transgenic controls. Contact hypersensitivity challenge responses in transgenic animals were characterized by an exaggerated lichenoid infiltration of monocytes and T cells. Additional phenotypic characterization of the normal appearing skin in these mice showed that the only spontaneous change was a dramatic increase and redistribution of CD45 + , I-A + cells that assumed a dendritic morphology in situ , including a subset that expressed markers characteristic of Langerhans cells. Taken together, these data indicate that tissue-specific expression of MCP-1 alone is not sufficient to induce an inflammatory response, though its presence can modify inflammatory and immune events initiated by exogenous stimuli. The recruitment of dendritic and Langerhans cells in the absence of inflammation is a previously unknown consequence of cutaneous MCP-1 production in vivo .
DISTINCT ROLES FOR THE ACTIN AND MICROTUBULE CYTOSKELETONS IN THE MORPHOGENESIS OF EPIDERMAL HAIRS DURING WING DEVELOPMENT IN DROSOPHILA

We have found that the actin and microtubule cytoskeletons have overlapping, but distinct roles in the morphogenesis of epidermal hairs during Drosophila wing development. The function of both the actin and microtubule cytoskeletons appears to be required for the growth of wing hairs, as treatment of cultured pupal wings with either cytochalasin D or vinblastine was able to slow prehair extension. At higher doses a complete blockage of hair development was seen. The microtubule cytoskeleton is also required for localizing prehair initiation to the distalmost part of the cell. Disruption of the microtubule cytoskeleton resulted in the development of multiple prehairs along the apical cell periphery. The multiple hair cells were a phenocopy of mutations in the inturned group of tissue polarity genes, which are downstream targets of the frizzled signaling/signal transduction pathway. The actin cytoskeleton also plays a role in maintaining prehair integrity during prehair development as treatment of pupal wings with cytochalasin D, which inhibits actin polymerization, led to branched prehairs. This is a phenocopy of mutations in crinkled, and suggests mutations that cause branched hairs will be in genes that encode products that interact with the actin cytoskeleton.
Origin of idling noise in circular saws and its suppression

This paper concerns the mechanism of noise generation and methods of noise reduction for idling circular saws. Experiments were conducted to examine the sources of saw noise. Saw resonant vibration is proven to be excited aerodynamically rather than by mechanical imbalance. The source of noise generated from a resonating saw and that generated from a nonresonating saw are shown to be identical. A mathematical model is proposed to formulate the dependence of the noise source upon saw kinematic and geometric parameters. Based upon this model and the associated experiments, several potential techniques for noise reduction through design of saw tooth geometry are recommended and discussed.