cssi/SciSciGPT-SciSciNet huggingface dataset:
The genomic landscapes of individual melanocytes from human skin

Abstract Every cell in the human body has a unique set of somatic mutations, yet it remains difficult to comprehensively genotype an individual cell. Here, we developed solutions to overcome this obstacle in the context of normal human skin, thus offering the first glimpse into the genomic landscapes of individual melanocytes from human skin. We comprehensively genotyped 133 melanocytes from 19 sites across 6 donors. As expected, sun-shielded melanocytes had fewer mutations than sun-exposed melanocytes. However, within sun-exposed sites, melanocytes on chronically sun-exposed skin (e.g. the face) displayed a lower mutation burden than melanocytes on intermittently sun-exposed skin (e.g. the back). Melanocytes located adjacent to a skin cancer had higher mutation burdens than melanocytes from donors without skin cancer, implying that the mutation burden of normal skin can be harnessed to measure cumulative sun damage and skin cancer risk. Moreover, melanocytes from healthy skin commonly harbor pathogenic mutations, likely explaining the origins of the melanomas that arise in the absence of a pre-existing nevus. Phylogenetic analyses identified groups of related melanocytes, suggesting that melanocytes spread throughout skin as fields of clonally related cells, invisible to the naked eye. Overall, our study offers an unprecedented view into the genomic landscapes of individual melanocytes, revealing key insights into the causes and origins of melanoma.
Inherent Bias in Artificial Intelligence-Based Decision Support Systems for Healthcare.

The objective of this article is to discuss the inherent bias involved with artificial intelligence-based decision support systems for healthcare. In this article, the authors describe some relevant work published in this area. A proposed overview of solutions is also presented. The authors believe that the information presented in this article will enhance the readers’ understanding of this inherent bias and add to the discussion on this topic. Finally, the authors discuss an overview of the need to implement transdisciplinary solutions that can be used to mitigate this bias.
Forensic genetics and ethical, legal and social implications beyond the clinic

Data on human genetic variation help scientists to understand human origins, susceptibility to illness and genetic causes of disease. Destructive episodes in the history of genetic research make it crucial to consider the ethical and social implications of research in genomics, especially human genetic variation. The analysis of ethical, legal and social implications should be integrated into genetic research, with the participation of scientists who can anticipate and monitor the full range of possible applications of the research from the earliest stages. The design and implementation of research directs the ways in which its results can be used, and data and technology, rather than ethical considerations or social needs, drive the use of science in unintended ways. Here we examine forensic genetics and argue that all geneticists should anticipate the ethical and social issues associated with nonmedical applications of genetic variation research.
The dynamics of a planar beating micro-swimmer constructed using functional fluid:

The dynamics of a flexible micro-swimmer that contains superparamagnetic beads of different diameter in an oscillating field is studied experimentally. Two types of artificial swimmers are fabricat...
MPN-087: Patient Characteristics and Treatment Patterns of Ruxolitinib (Rux) Among 37 Patients with Essential Thrombocythemia (ET) in Real-World Clinical Practice: A Chart Review

Context: ET is a Philadelphia-chromosome negative myeloproliferative neoplasm (MPN). Cytoreductive therapy (e.g., hydroxyurea [HU]) is recommended for management of high-risk patients. Rux (JAK1/2 inhibitor) is indicated for other MPNs (i.e., myelofibrosis and polycythemia vera). Objective: To describe characteristics and treatment patterns in patients receiving rux for ET in real-world practice. Design: Retrospective chart review of patients diagnosed with ET between 06/2011–09/2016 who received cytoreductive therapy at 50 community practices. Results: Thirty-seven patients received rux for ET (at diagnosis: median age, 67 [range, 42–82] years; high-risk, 76%; JAK2+, 91% [19/21], MPL+, 27% [4/15], CALR+, 7% [1/14]; WBC ≥11 × 109/L, 57%; platelets ≥600 × 109/L, 95%). Ten patients received rux as 1st-line; 25 as 2nd-line; 1 each as 3rd- and 4th-line. All 25 patients initiating 2nd-line rux received 1st-line HU. Sixteen patients discontinued HU, then commenced rux (median time from HU discontinuation to rux initiation, 23.5 [range, 0–212] days); 8 added rux after a median 16.5 (2–49) months of HU therapy; 1 discontinued HU ∼1 month after rux initiation. Reasons for HU discontinuation (n=16) included primary resistance (56%) and intolerance (44%). For the 37 patients, median duration from diagnosis to rux initiation was 10 (range, 0–294) months (most common starting doses, 10 mg BID [38%]; 20 mg BID [32%]). Common clinical reasons for prescribing rux included high platelets (43%), constitutional symptoms (41%), splenomegaly, and spleen-related symptoms (38% each). Thirty-four patients (92%) remained on rux at last visit. Median duration of rux treatment was 6.5 (range, 0–32) months. All documented ET symptoms improved markedly from rux initiation to last visit (73% vs 43% had any symptom; most common symptom, fatigue [49% vs 30%]), as did platelets ≥600 × 109/L (95% vs 3%) and WBC ≥11 × 109/L (57% vs 19%). Per physician assessment, all 34 assessed patients responded to rux (17 complete; 17 partial; median time from rux initiation to best response, 3 [range, 1–10] months). Conclusion: In patients with ET receiving rux spontaneously in real-world practice, most initiated rux after HU resistance/intolerance and most continued rux for ≥6 months. All patients assessed achieved responses and experienced clinical benefit from rux per physician assessment.
The role of eye contact in young children's judgments of others' visibility: A comparison of preschoolers with and without autism spectrum disorder.

Abstract Typically-developing (TD) children under age 5 often deny that they can see a person whose eyes are covered (e.g., Moll & Khalulyan, 2017 ). This has been interpreted as a manifestation of their preference for reciprocal interactions. We investigated how 3- to 4-year-old children with autism spectrum disorder (ASD, n = 12) respond in this situation. Because a lack of interpersonal connectedness and reciprocal communication are core features of this disorder, we predicted that young children with ASD will not make mutual regard a condition for seeing another person and therefore acknowledge being able to see her. Against this prediction, children with ASD gave the same negative answers as a group of TD (n = 36) age-mates. Various interpretations are discussed, including the possibility that some children with ASD are capable of relating to others as second persons.
Knowledge, Awareness and Probabilistic Beliefs

Bayesian game theory investigates strategic interaction of players with full awareness but incomplete information about their environment. We extend the analysis to players with incomplete awareness, who might not be able to reason about all contingencies in the first place. We develop three logical systems for knowledge, probabilistic beliefs and awareness, and characterize their axiom systems. Bayesian equilibrium is extended to games with incomplete awareness and we show that it is consistent with common prior and speculative trade, when common knowledge of rationality is violated.
Predicting Middle School Profiles of Algebra Performance Using Fraction Knowledge

Fraction knowledge and algebraic skill are closely linked. Algebra is a gatekeeper for advanced courses (Booth & Newton, 2012; Brown & Quinn, 2007). This study uses the person-centered approach of latent profile analysis to examine individual differences in middle schoolers' (N = 350) algebra performance at the end of the year (EOY). The relative importance of a range of fraction skills is considered in predicting the likelihood of displaying a particular profile of EOY algebra knowledge, measured by feature knowledge, equation encoding, equation solving, and word-problem skills. Notably, fraction number line estimation did not predict algebra performance on any of the four measures. Fraction arithmetic at the beginning of the year is most predictive of displaying the highest performing EOY algebra profile.
Association of body composition parameters measured on CT with risk of hospitalization in patients with Covid-19.

PURPOSE: To assess prognostic value of body composition parameters measured at CT to predict risk of hospitalization in patients with COVID-19 infection. METHODS: 177 patients with SARS-CoV-2 infection and with abdominopelvic CT were included in this retrospective IRB approved two-institution study. Patients were stratified based on disease severity as outpatients (no hospital admission) and patients who were hospitalized (inpatients). Two readers blinded to the clinical outcome segmented axial CT images at the L3 vertebral body level for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), muscle adipose tissue (MAT), muscle mass (MM). VAT to total adipose tissue ratio (VAT/TAT), MAT/MM ratio, and muscle index (MI) at L3 were computed. These measures, along with detailed clinical risk factors, were compared in patients stratified by severity. Various logistic regression clinical and clinical + imaging models were compared to discriminate inpatients from outpatients. RESULTS: There were 76 outpatients (43%) and 101 inpatients. Male gender (p = 0.013), age (p = 0.0003), hypertension (p = 0.0003), diabetes (p = 0.0001), history of cardiac disease (p = 0.007), VAT/TAT (p < 0.0001), and MAT/MM (p < 0.0001), but not BMI, were associated with hospitalization. A clinical model (age, gender, BMI) had AUC of 0.70. Addition of VAT/TAT to the clinical model improved the AUC to 0.73. Optimal model that included gender, BMI, race (Black), MI, VAT/TAT, as well as interaction between gender and VAT/TAT and gender and MAT/MM demonstrated the highest AUC of 0.83. CONCLUSION: MAT/MM and VAT/TAT provides important prognostic information in predicting patients with COVID-19 who are likely to require hospitalization.
Ribosomal RNAs and Protein Synthesis

Protein synthesis is a cellular process essential for life. Ribosomes are responsible for protein synthesis in all cells. Ribosomes are composed of three RNA molecules (23S, 16S, and 5S ribosomal RNAs) and about 50 proteins. The ribosomal RNAs play a central role in protein synthesis by forming the active site for peptide bond formation and by interacting with messenger RNA, transfer RNA, and translational factors. Here we describe the functional role of the ribosomal RNAs in protein synthesis.
Activation of thyroid membrane adenylate cyclase by purine nucleotides.

Abstract The effect of purine and pyrimidine nucleotides on the activation of adenylate cyclase by thyrotropin and prostaglandin E1 in beef thyroid plasma membranes was investigated. At 1 mm ATP concentration, GTP increases basal and thyrotropin-stimulated activity 2- to 4-fold at concentrations of 1 to 30 µm. Significant stimulation occurs at 0.1 µm. Greater maximal stimulation occurs with ITP (5- to 7-fold) over the concentration range of 20 to 50 µm. In order of decreasing maximal effect the nucleoside triphosphates are ITP g dGTP g GTP g XTP. At low concentrations GTP g ITP. Pyrimidine nucleotides had low activity. The enhancement occurs also with IDP and GDP and at 1 mm with 5'-IMP and 5'-GMP. The ITP and IDP effects have a 1 to 2 min lag period before they become manifest. F--activated cyclase is not stimulated and is partially inhibited at high nucleotide concentrations; thus, thyrotropin-stimulated cyclase may exceed F--stimulated activity in some conditions. Prostaglandin E1-stimulated activity is also enhanced by these nucleotides but, in contrast to thyrotropin activity, maximal stimulation by GTP = dGTP = ITP g XTP. Potassium ion increases thyrotropin-stimulated adenylate cyclase in the presence of 20 µm ITP, whereas there is no K+ effect on stimulation evoked by prostaglandin E1 even in the presence of ITP. Furthermore, the prostaglandin and thyrotropin stimulations are additive in the absence and in the presence of ITP and GTP. It is concluded that the nucleotides interact with the cyclase system not at the catalytic site, that the nucleotides can interact at more than one site, and that the thyrotropin and prostaglandin receptors are probably separate.
A virtual reality laboratory for undergraduates

Virtual reality (VR) is an emerging field with many exciting applications. Despite its growing popularity, VR is often neglected in most undergraduate computer science programs. This paper presents several resources to support low-cost virtual reality and describes the VR laboratory at the author's institution. Topics discussed in this paper include stereo projection systems, tracking, and haptics, with an emphasis on low-cost implementations that are possible at most institutions.
An integrative framework for the identification of double minute chromosomes using next generation sequencing data.

Double minute chromosomes are circular fragments of DNA whose presence is associated with the onset of certain cancers. Double minutes are lethal, as they are highly amplified and typically contain oncogenes. Locating double minutes can supplement the process of cancer diagnosis, and it can help to identify therapeutic targets. However, there is currently a dearth of computational methods available to identify double minutes. We propose a computational framework for the idenfication of double minute chromosomes using next-generation sequencing data. Our framework integrates predictions from algorithms that detect DNA copy number variants, and it also integrates predictions from algorithms that locate genomic structural variants. This information is used by a graph-based algorithm to predict the presence of double minute chromosomes. Using a previously published copy number variant algorithm and two structural variation prediction algorithms, we implemented our framework and tested it on a dataset consisting of simulated double minute chromosomes. Our approach uncovered double minutes with high accuracy, demonstrating its plausibility. Although we only tested the framework with three programs (RDXplorer, BreakDancer, Delly), it can be extended to incorporate results from programs that 1) detect amplified copy number and from programs that 2) detect genomic structural variants like deletions, translocations, inversions, and tandem repeats. The software that implements the framework can be accessed here: https://github.com/mhayes20/DMFinder
Moving Least-Squares: A Numerical Differentiation Method for Irregularly Spaced Calculation Points

Numerical methods may require derivatives of functions whose values are known only on irregularly spaced calculation points. This document presents and quantifies the performance of Moving Least-Squares (MLS), a method of derivative evaluation on irregularly spaced points that has a number of inherent advantages. The user selects both the spatial dimension of the problem and order of the highest conserved moment. The accuracy of calculations is maintained on highly irregularly spaced points. Not required are creation of additional calculation points or interpolation of the calculation points onto a regular grid. Implementation of the method requires the use of only a relatively small number of calculation points. The method is fast, robust and provides smooth results even as the order of the derivative increases.
Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully 13C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the labeling patterns of acetyl-CoA proxies, i.e. total acetyl-CoA, the acetyl moiety of citrate, C-1 + 2 of β-hydroxybutyrate, malonyl-CoA, and acetylcarnitine. Additional information was obtained from the labeling patterns of citric acid cycle intermediates and related compounds. The data characterize the partial oxidation of DODA and azelate in peroxisomes, with terminal oxidation in mitochondria. We did not find evidence of peroxisomal oxidation of glutarate. Unexpectedly, DODA contributes a substantial fraction to anaplerosis of the citric acid cycle. This opens the possibility to use water-soluble DODA in nutritional or pharmacological anaplerotic therapy when other anaplerotic substrates are impractical or contraindicated, e.g. in propionic acidemia and methylmalonic acidemia.
Resonant Rayleigh scattering by a quantum well: time-domain theory

Summary form only given. We investigate the roles of two length scales in the dynamics of the resonantly scattered light from a quantum well (QW); namely the scale associated with the size of the typical interface defect-or island-and that associated with spatial correlations between islands. Explicit time- and wave vector-dependent expressions for the scattered light amplitude and intensity are obtained. We find that a substantial portion of the light is scattered into nonradiative surface polariton modes, whose electromagnetic character is evanescent in the direction away from the QW.
Adaptively Secure Multi-Party Computation with Dishonest Majority

Adaptively secure multiparty computation is an essential and fundamental notion in cryptography. In this work we focus on the basic question of constructing a multiparty computation protocol secure against a malicious, adaptive adversary in the stand-alone setting without assuming an honest majority, in the plain model. It has been believed that this question can be resolved by composing known protocols from the literature. We show that in fact, this belief is fundamentally mistaken. In particular, we show:Round inefficiency is unavoidable when using black-box simulation: There does not exist any $$o\frac{n}{\log {n}}$$ round protocol that adaptively securely realizes a natural n-party functionality with a black-box simulator. Note that most previously known protocols in the adaptive security setting relied on black-box simulators.A constant round protocol using non-black-box simulation: We construct a constant round adaptively secure multiparty computation protocol in a setting without honest majority that makes crucial use of non-black box techniques. Taken together, these results give the first resolution to the question of adaptively secure multiparty computation protocols with a malicious dishonest majority in the plain model, open since the first formal treatment of adaptive security for multiparty computation in 1996.
Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury.

Object Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors' objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value. Methods A prospective study of patients with severe TBI was conducted with an inclusion criterion of a Glasgow Coma Scale score ≤ 8 within 48 hours of injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO2, jugular venous O2 saturation, and cerebral microdialysis. Patients received standard care including mass evacuation when indicated and treatment of elevated intracranial pressure values. Demographic data, CT findings, and outcome at 6 months of follow-up were recorded. Results One hundred sixty-five patients were included in the ...
Absorption, metabolism, and transport of carotenoids.

Carotenoids are currently under intense scrutiny regarding their potential to modulate chronic disease risk and prevent vitamin A deficiency, and renewed emphasis has been placed on achieving a better understanding of the metabolic fate of these compounds in humans. The development of new animal models, and use of human metabolic studies and stable tracer methods have greatly improved our knowledge of how carotenoids are absorbed, metabolized, and transported to tissues; however, many important issues remain unresolved. For example, intestinal uptake of carotenoids occurs by passive diffusion, but the lumenal or intracellular factors limiting this process are obscure. The intestinal mucosa plays a key role in the metabolism of provitamin A carotenoids such as beta-carotene, thus greatly influencing their bioavailability. Most recent evidence supports a central oxidation mechanism of cleavage of beta-carotene to retinal in the intestinal mucosa, but the extent and site(s) of postabsorptive metabolism in th...
Proliferation and enrichment of CD133+ glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds

Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anti-cancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GBM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs. CA scaffold-grown cells were found more tumorigenic in nude mouse xenografts than cells grown from monolayers. Growing in CA scaffolds rapidly promoted expression of genes involved in the epithelial-to-mesenchymal transition that has been implicated in the genesis of CSCs. Our results indicate that CA scaffolds have utility as a simple and inexpensive means to cultivate CSCs in vitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.
Anabolic steroids and aggressive behavior in cynomolgus monkeys

An animal model was employed to examine the effect of testosterone on aggressive behavior patterns. Ten cynomolgus monkeys were assigned to either an experimental or a control group and given biweekly injections; the experimental group received testosterone propionate, and the controls a sham solution. Prior to and upon the completion of an 8-week treatment period, behavioral observations were conducted. Although the administration of testosterone resulted in a significant increase in aggression, more important was the finding that changes in behavior were mediated by social status; that is, the incidence of both contact and noncontact aggression in dominant monkeys was far greater than the frequency of these behaviors in subordinate monkeys. These data are discussed in terms of the potential role of anabolic steroids as a risk factor in cardiovascular disease.
The impact of consecutive operations on survival after liver transplantation.

The impact of surgeon fatigue on patient outcomes has not been previously studied. In order to assess the relationship of surgeon workload to patient outcome, we analyzed the impact of the interval between liver transplants and the cumulative number of liver transplants in a week on patient outcome. The outcomes of 390 liver transplants performed between 2003 and 2006 at the University of Washington Medical Center were analyzed. Overall 1-year patient/graft survival was significantly higher if the primary surgeon had >2 days between transplants ( 2 days between transplants, 92.5%/91.2%, P or =4 (90.4% versus 80.9%, P < 0.026). No other analyzed complication reached significance. Surgeon fatigue from successive transplants may potentially affect liver transplant survival. Call schedules should recognize the potential impact of workload on liver transplant outcome. Liver Transpl 15:907-914, 2009. (c) 2009 AASLD.
Cooperative interactions of histamine and competitive antagonism by cimetidine at neuronal histamine receptors in the marine mollusc, Aplysia californica.

Abstract Dose-response curves and Hill plots were used to analyze the interaction between histamine (HA), two HA agonists and an HA antagonist, and the HA receptors mediating membrane hyperpolarizations in Aplysia neurons. Dose-response curves for both HA and the HA agonists (2-methylhistamine and 4-methylhistamine) were sigmoidal and the corresponding Hill plots had slopes greater than one (mean = 2). This result is interpreted as evidence for a cooperative type of interaction between HA and HA agonists and the neuronal HA receptors. Cimetidine (10 −6 to 4 × 10 −6 M), an HA antagonist, produced reversible, dose-dependent, parallel shifts in the HA dose-response curves. Modified Schild plots constructed from this data were linear. These results demonstrate that cimetidine is a competitive antagonist at the neuronal HA receptors. The slope of the modified Schild plots, which gives an estimate of the minimum number of antagonist molecules that interact with each receptor, was greater than one (mean = 1.7). This result is interpreted as evidence for a cooperative type of interaction between cimetidine and the neuronal HA receptors.
A biomechanical analysis of gap formation and failure mechanics of a xenograft-reinforced rotator cuff repair in a cadaveric model

Hypothesis Failure rates of rotator cuff repairs are reported to be as high as 90%, in part because of gap formation at the repair site that occurs before healing. The purpose of this study was to evaluate whether the application of an extracellular matrix (ECM) graft (Conexa; Tornier, Edina, MN, USA) to a rotator cuff repair will decrease the gap formation at the tendon-bone interface and increase the ultimate load to failure over control specimens by mechanically sharing load with the repair in a cadaveric model. Methods Six pairs of human cadaveric shoulders were used to test ECM-reinforced and unreinforced rotator cuff repairs for repair-site gapping, ultimate load, failure mode, and load-sharing capabilities of the ECM patch under both cyclic and monotonic loading. Results The gap formation under cyclic loading was reduced by 40% for the reinforced specimens compared with the control group (1.3 ± 0.6 mm vs 2.1 ± 0.5 mm, P P P Conclusions Application of an ECM graft to a rotator cuff repair decreased tendon gapping and increased load to failure by load sharing in a human rotator cuff repair model.
What we talk about when we talk about content externalism

Some content externalists claim that if C is a theoretical concept and “C” expresses C, then the content of C in a community at a time is determined by how some members of the community at the time—call them “experts”—understand C or use “C”. Thus, when non-expert Chauncey utters “C”, the content of the concept he expresses does not depend entirely on his intrinsic physical properties, contra the claims of content internalism. This paper proposes that “concept” expresses a theoretical concept, such that the externalist’s insights should apply to how we understand claims expressing the view itself and to how we evaluate the arguments alleged to motivate it. With respect to the first, I argue that the content externalist (a) should regard it as unclear at present which proposition her theory expresses, and (b) should take it that content externalism teaches us about our linguistic community rather than about the metaphysical nature of concepts. With respect to the second, I argue that by externalism’s own lights, the famous externalist thought experiments shouldn’t establish content externalism. In conclusion, I suggest that making sense of content externalism requires presupposing internalism.
Clinical laboratory evaluation of deep mycotic diseases in dogs

A retrospective study of 27 dogs with deep mycoses was conducted to evaluate the usefulness of initial laboratory results in determining a diagnosis. Fifteen cases of disseminated blastomycosis, five cases of disseminated histoplasmosis and seven cases of gastrointestinal phycomycosis were studied. Haematologic results consistent with a chronic inflammatory disease (mild to moderate anaemia and moderate to marked monocytosis) were common findings in blastomycosis and phycomycosis. Cases of histoplasmosis were characterized by a more severe anaemia with a neutrophilia and left shift. The severe anaemia present in three out of five (3/5) dogs with histoplasmosis was apparently due to myelophthisis and intravascular erythrocyte fragmentation. Coagulation function tests and/or the haemograms suggested the presence of microangiopathic haemolysis in four dogs with histoplasmosis. Clinical chemistry results in blastomycosis and phycomycosis were usually unremarkable. Hepatic lesions in histoplasmosis were suggested by increases in serum alkaline phosphatase and decreases in serum albumin. Cytology was frequently diagnostic for blastomycosis (11/13 cases) and histoplasmosis (3/4 cases) but was inconsistent in phycomycosis (1/3 cases).
Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells.

The transcription factor Foxo1 controls the expression of genes involved in fundamental cellular processes. In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208–652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. Insulin inhibition of Foxo1-(208–652)-stimulated transactivation is mediated by PI 3-kinase but in contrast to full-length Foxo1, does not require either of the two PKB/Akt phosphorylation sites (Ser253 and Ser316) present in the protein fragment. Using mutational and deletion studies, we identify two potential phosphorylation sites, Ser319 and Ser499, as well as a 15-amino acid region located between residues 350 and 364 that are critical for insulin inhibition of transactivation by Foxo1-(208–652). We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. These different regulatory mechanisms allow the precise control of transcription of Foxo1 target genes by insulin.
Streptozotocin-diabetes alters action potentials in rat diaphragm.

This study tested the hypothesis that diabetes alters diaphragm action potentials and electrophysiological responses to K+ channel blockade. Intracellular recordings were performed in vitro in diaphragm fibers from streptozotocin-induced diabetic and normal Wistar rats (glucose 670±31 vs. 252±14 mg/dl). Comparing diabetic to normal muscle properties, resting membrane potential was significantly depolarized (−72.2±0.8 vs. −77.4±1.1 mV), action potential 50% repolarization time was significantly accelerated (0.33±0.01 vs. 0.39 ±0.01 msec), and action potential area was significantly decreased (59.4±2.3 vs. 70.7±2.2 mV msec). The K+ channel blocker 3,4-diaminopyridine (DAP) depolarized resting membrane potential of normal but not diabetic muscle. DAP significantly prolonged action potential repolarization and significantly increased action potential area, but significantly more in normal than diabetic muscle. These data indicate that diabetes shortens diaphragm action potentials, which appears to be due to altered K+ channels.
Epinephrine-Induced Excitation and Sensitization of Rat C-Fiber Nociceptors

Abstract Although epinephrine (EPI) has been suggested to contribute to the pain and hyperalgesia associated with inflammation and nerve injury, there have been very few in vivo electrophysiologic studies of the effects of EPI on nociceptors. We found with the single-unit recording technique that the intradermal administration of EPI resulted in excitation of a group of C fibers and a decrease in the mechanical activation threshold in a non-overlapping group. Unexpectedly, the fibers that were neither excited nor demonstrated a decrease in threshold demonstrated as a group a significant increase in response to sustained suprathreshold mechanical stimuli, an effect not observed in the other 2 groups of C fibers. This identifies a novel response of C-fiber nociceptors to an inflammatory mediator and suggests it is present in a class of C fibers previously considered unresponsive to hyperalgesic inflammatory mediators. Perspective Our study provides support for the suggestion that EPI, a neuroendocrine stress hormone as well as an inflammatory mediator, might contribute to pain syndromes, especially in the setting of chronic stress.
Scyphistoma Regeneration From Isolated Tentacles in Aurelia Aurita

All animals do not display the same capacities for repairing injuries, i.e. they possess what may be termed different ‘regeneration potentials’. One parameter influencing the regeneration potential manifested by an organism is its developmental history, or ontogeny. Early in an animal's ontogeny many of its cells are still undergoing both structural and biochemical modifications. As the animal matures, its cells become increasingly differentiated, ultimately attaining a high degree of specialization (Hay, 1966; Balinsky, 1970).Numerous studies support the contention that the younger an animal ontogenically, the greater is its regeneration potential. Investigations using amphibians have presented several cogent examples of this generalization (Balinsky, 1970). Analogous situations are also evident in the Cnidaria. In the hydrozoan, Hydra, the tentacles contain what are among the ontogenically ‘oldest’ cells in the organism (Tripp, 1928; Brien & Reniers-Decoen, 1949; Burnett, 1966; Campbell, 1967b). Unlike the remainder of the organism, these structures also reportedly possess no regeneration potential (Peebles, 1897; Kanaev, 1952).Three explanations have been proposed to account for the absence of regeneration potential in isolated tentacles. Nussbaum (cited in Kanaev, 1952) suggested that the absence of interstitial cells in the tentacles precluded regeneration. However, other regions of the animal, when experimentally deprived of this cell type, retained their regenerative capacities (Brien, 1953; Diehl & Burnett, 1964).A second explanation invoked the size of an isolated tentacle as a factor limiting regeneration. In disputing this suggestion, Peebles (1897) measured tentacle volume. Isolated Hydra grisea (Pallas) tentacles ranged from 0.01 to to 0.03 mm3, while the volume of the smallest body fragment capable of total regeneration was considerably smaller, 0.006 to 0.01 mm3. From these measurements she concluded that the size of isolated tentacles could not account for the inability to regenerate.
Frequency response analysis of nonlinear tapping-contact mode atomic force microscopy

The nonlinear vibrations of the tapping-mode atomic force microscopy probe are investigated due to both nonlinearity in tip–sample contact force and curvature of the microcantilever probe. The nonlinear equations of motion for vibrations of the probe are obtained using Hamilton’s principle. In this work, the contact force is considered to be more dominant while previous works only consider Van der Waals force. The nonlinear contact force is expanded using a Taylor series to provide a polynomial with coefficients that are functions of the tip–sample distance. The outcome of this work allows the proper distance to be chosen before scanning to avoid instability in the response. Instability regions must be avoided for accurate imaging. The results show that initial tip–sample distance has a major effect on the stability of the frequency response and force response curves. For analytical investigation, the mode shapes of the atomic force microscopy probe are derived based on the presence of the nonlinear conta...
Inferring flow types from dye patterns in macroporous soils

In this study, we exploit dye patterns to identify flow types in macroporous soils as a step forward from using dye patterns simply as qualitative pictures that illustrate preferential flow. Dye tracer experiments at different irrigation rates and initial soil moisture conditions were carried out on three hillslope sites. Several vertical and horizontal soil sections were prepared after each experiment to analyze the patterns of the dye tracer Brilliant Blue FCF. Photographs of the soil sections were processed by image analysis to discriminate between stained and unstained areas and to classify stained areas into three classes of dye concentration. The images of the vertical sections were first analyzed according to conventional approaches (e.g., dye coverage). Then, a new approach was developed using the extent and distribution of the stained objects to classify flow into five types, two of these flow types occur only in the soil matrix, and three of them are related to the degrees of water flow between macropores and soil matrix (interaction). From horizontal sections, the macropore distribution was classified and, in combination with the dye pattern, the interaction quantified based on statistical description of the spatial relationship between macropores and stained areas. Categorized flow type profiles showed a logical sequence in each of our experiments, and we think the concepts will have broad application in soil science and infiltration research to compare the infiltration regimes of soils.
Portfolio assessment of intercultural competence

Abstract Portfolio assessment has been gaining prominence among U.S. educators as a valuable tool for authentic assessment. Whereas more traditional forms of assessment attempt to somehow quantify students’ learning, portfolio assessment recognizes that learning is not always easily quantifiable, and calls on students to demonstrate their learning by selecting and presenting examples of their best work. This paper describes our procedures for introducing, developing, evaluating intercultural communication skills portfolios with our Intensive English Program students at The University of Iowa. We have found portfolio assessment to be well-suited for promoting our students’ awareness of and reflection on their intercultural learning. Based on our initial experience using portfolios for this purpose, we recognize three distinct types of intercultural learning among our students, and offer suggestions for using portfolio assessment in intercultural education settings.
Preventing Crime with Prenatal and Infancy Support of Parents: The Nurse-Family Partnership

Abstract Pregnancy and the early years of a child's life offer an opportune time to prevent a host of adverse outcomes that are important in their own right, but that also have significant implications for the development of criminal behavior. This paper summarizes a 27-year program of research that has attempted to improve early maternal and child health and future life prospects with prenatal and infancy home visiting by nurses. The program, known today as the Nurse-Family Partnership (NFP), is designed for low-income mothers who have had no previous live births. The home visiting nurses have three major goals: to improve the outcomes of pregnancy by helping women improve their prenatal health; to improve the child's health and development by helping parents provide more sensitive and competent care of the child; and to improve the parental life course by helping parents plan future pregnancies, complete their educations, and find work. Given consistent effects on prenatal health behaviors, parental car...
Beneficial effects of potassium cardioplegia during intermittent aortic cross-clamping and reperfusion.

Abstract Aortic cross-clamping is an essential adjunct to a variety of cardiac surgical procedures requiring a quiet flaccid heart and avoidance of systemic air embolism. The consequences of excluding the heart from perfusion, oxygen, and substrate are time dependent and lead ultimately to irreversible damage of the myocardium. The goal of complete preservation of myocardial function and metabolism during ischemia has not been realized even with the best clinically applicable techniques. The present study was designed to evaluate the effects of sequential aortic cross-clamping interrupted by reperfusion similar to that used in clinical practice. The advantages of induced cardiac arrest with potassium chloride solution at the onset of aortic cross-clamping were assessed in a second group of animals. A total of 27 mongrel dogs supported by normothermic cardiopulmonary bypass was subjected to four aortic cross-clamp periods interrupted by 5-min reper-fusion periods. The study included an evaluation of left ventricular performance using an isovolumic balloon technique and an assessment of myocardial metabolism using “stop-freeze” biopsies and biochemical assay for ATP, ADP, AMP, and creatine phosphate. The data demonstrate that repeated induction of ischemic arrest results in profound depletion of adenine nucleo-tides and severe depression of contractility. Using potassium-induced cardiac arrest, normal contractile function is preserved along with conservation of adenine nucleo-tides, suggesting that even at normothermia, preservation of the heart during ischemia can be achieved.
Re-donation intentions among experienced blood donors: Does gender make a difference?

Path analysis was used to examine sex differences in motivation for repeat donation among experienced blood donors. Results confirm the importance of constructs from the Theory of Planned Behavior (e.g., donation attitude, subjective norm, personal moral norm, and donation self-efficacy) and of prior donation experience (e.g., vasovagal symptoms, overall satisfaction) as significant predictors of donation intention. Importantly, the findings also indicate that a consideration of sex differences in donor motivations results in a better prediction model and suggests a framework of possible avenues where interventions could be expected to improve donor return rates.
Visualizing Sustainability In Urban Conditions

Cities present many challenges for the environmentally conscious designer. Sustainability is a complex issue comprised of many overlapping and sometimes contradictory concerns. Overlaid on the inherent complexity of the urban environment, questions of sustainability become even more opaque – lost in a multifaceted network well described by Hough. In such conditions it becomes very difficult for even well informed and well intentioned designers to understand the ramifications of their actions. One of the primary difficulties of sustainable practice in urban conditions is that many of the aspects of urban sustainability are invisible – take for example walkability which may have visible components such as quality of sidewalk or intensity of vehicular traffic but also has many factors that are invisible or not readily seeable such as climate, topography that extends beyond the immediate site, and distribution of amenities. This paper presents research intended to inform designers in the earliest stages of design by making several of these factors visible. Using geographic information visualization (GIV) software multiple aspects of urban sustainability are mapped and visualized. This mapping of previously invisible or partially visible issues in the form of geospatial information provides architects and urban designers with the ability to process and understand information about a particular neighborhood’s sustainability through the means with which they are most accustomed – visual information. As way of example, this research focuses on a particular inner ring neighborhood in Knoxville, Tennessee, USA.
Solvent extraction of cottonseeds with hexane and water as co‐solvents

By stirring violently for four hours at 4,100 r.p.m. a mixture of dehulled and flaked cottonseed meal, hexane, and water, with respective hexane/meal and water/meal weight ratios of 6:1 and 1:5, all the pigment glands of the seed are broken, the oil content of the meal is reduced to about 1%, and a miscella phase only, free of water, is produced as all the water added remains with the meal. Extracted meal thus obtained is easily filtered from the miscella and air-dries to an easily handled, non-sticky cake. If the water is increased in the mixture to a water/meal ratio of 2:5, other results remain about the same, but the meal is excessively sticky and is difficult to filter from the miscella. Pre-soaking the meal in solvent before extraction has little or no effect, under our conditions of extraction, on the amount of oil left in the meal.
A pragmatic model to estimate journal quality in accounting

Abstract This article presents a model to estimate the relative quality of publication outlets based on objective journal characteristics. Our model improves upon the one proposed by Bean and Bernardi [Bean, D. F., & Bernardi, R. A. (2005). Estimating the ratings of journals omitted in prior quality ratings. Advances in Accounting Education, 7, 109–127.] in three important ways. First, we develop a dependent variable that is a composite score based on five prior journal perception studies. Second, our model considers different independent variables; audience, journal availability, inclusion in the Social Sciences Citation Index (an independent measure of quality), and the journal’s submission fee. This combination of variables increases the model’s explanatory power by 21% compared to Bean and Bernardi’s average R2. Finally, the results of our model are more consistent with those of prior perception studies. We also apply the model to recent accounting faculty publications, which provides a comparative rating of more than 200 journals. We expect our model for estimating journal quality to help faculty, promotion and tenure committees, and university administrators evaluate the quality of journals where accounting faculty publish, an important aspect of assessing research productivity.
Impacts on balance when walking in occupational footwear

Hazards and challenges present in the workplace pose a number of potential balance risks for injuries and illness.Purpose: The purpose of the study was to examine the differences in balance while walking for extended durations with different types of occupational footwear.Methods: Participants were tested for balance prior to walking session (Pre) and then again every 30 minutes until the 240th minute in three types of occupational footwear; work boots, tactical boots and low top shoes. Sway velocity and root-mean-square sway in the anterior-posterior and medial-lateral directions were evaluated using a 3 × 9 repeated measures analysis of variance to identify any existing differences within exposure time and footwear types.Results: Significant differences in postural sway were found over time in medial-lateral sway and between footwear in anterior-posterior and medial-lateral sway. Significant differences were found between the work boots, tactical boots and low top shoes, with the low top shoes exhibitin...