cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract P052: Parkin Deficiency Results in Disarray of the Mitochondrial Network and Increased Susceptibility to Myocardial Infarction

Parkin is an E3 ubiquitin ligase that was recently discovered to be involved in mitochondrial turnover via autophagy. Although Parkin has been characterized in the setting of neurodegenerative diseases, it is expressed in many other tissues including the heart. In this study, we have investigated the functional role of Parkin in the myocardium using global Parkin knockout (PKO) mice. We found that PKO mice have no overt cardiac phenotypes under normal conditions. Echocardiography showed normal left ventricular fractional shortening (38.82 3.55% for PKO vs. 39.89 1.19% for WT) and ejection fraction (68.53 4.21% for PKO vs. 71.27 1.60% for WT) at 12 weeks of age. Cardiac mitochondria isolated from PKO mice had normal respiratory rates and displayed normal coupling. Additionally, Parkin deficient mitochondria were as susceptible to mitochondrial permeability transition pore (mPTP) opening as WT mitochondria. However, mitochondria from PKO mice had higher baseline absorbance values than WT mitochondria (0.66 0.02 for PKO vs. 0.59 0.02 for WT), suggesting a smaller morphology. Ultrastructural analysis by transmission electron microscopy (TEM) confirmed a disorganized mitochondrial network with the presence of clusters of small mitochondria at 12 weeks of age in PKO hearts. At 6 months, PKO mice displayed a decline in cardiac function, and TEM revealed the presence of degenerating mitochondria. Although PKO mice have normal cardiac function at 12-weeks, they were very susceptible to stress. The PKO mice developed more severe dilated cardiomyopathies with reduced survival rates compared to WT in response to myocardial infarction. These data demonstrate that Parkin is involved in the maintenance of the mitochondrial network in the myocardium, and that Parkin deficiency exacerbates stress-induced heart failure. Given the role of Parkin in mitochondrial turnover, Parkin deficiency may result in a gradual decline of mitochondrial quality, the effects of which may surface under conditions of acute stress.
Hyperglycemia-induced hyponatremia: Reevaluation of the Na + correction factor.

This study addresses the clinically important relationship between the decreases in plasma Na+ and the increases in plasma glucose concentrations seen in diabetes and other hyperglycemic syndromes. This plasma 'Na+ correction factor', is generally accepted as 1.6mM Na+ per 100mg% glucose (0.29mM/mM in SI units) assuming osmotic equilibrium, although much larger numbers have been measured in experiments on normal humans. To resolve this controversy, a mathematical model of whole-body fluid-electrolyte balance was used to perform the experiment wherein plasma glucose concentration was increased to diabetic levels and the plasma Na+ concentration changes assessed, without the complications seen in human experiments. The findings, based on osmotic grounds, were that the factor 1) was significantly <1.6, approaching 1 in some cases, 2) depended upon the anthropometry of the subject; it was inversely proportional to the ratio of extracellular to total body water, which increases with higher fat content and 3) was approximately linear up to glucose concentrations of about 800mg%, but decreased up to 10% for higher glucose concentrations. To explain the experimental data, a hypothesis of Na+ sequestration in cells was incorporated in the model, resulting in close prediction of measured transient Na+ changes.
Targeting Wall Teichoic Acid in Situ with Branched Polyethylenimine Potentiates β-Lactam Efficacy against MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a medical concern. Here, we show that branched polyethylenimine (BPEI), a nontoxic, cationic polymer, restores MRSA’s susceptibility to β-lactam antibiotics. Checkerboard assays with MRSA demonstrated synergy between BPEI and β-lactam antibiotics. A time-killing curve showed BPEI to be bactericidal in combination with oxacillin. BPEI did not potentiate efficacy with vancomycin, chloramphenicol, or linezolid. When exposed to BPEI, MRSA increased in size and had difficulty forming septa. BPEI electrostatically binds to wall teichoic acid (WTA), a cell wall anionic polymer of Gram-positive bacteria that is important for localization of certain cell wall proteins. Lack of potentiation in a WTA knockout mutant supports the WTA-based mechanism. These data suggest that BPEI may prevent proper localization of cell wall machinery by binding to WTA; leading to cell death when administered in combination with β-lactam antibiotics. Negligible in vitro toxicity sug...
Evaluating oral flavorant effects on nicotine self-administration behavior and phasic dopamine signaling.

Understanding how tobacco product flavor additives, such as flavorants in electronic cigarettes, influence smoking behavior and addiction is critical for informing public health policy decisions regarding tobacco product regulation. Here, we developed a combined intraoral (i.o.) and intravenous (i.v.) self-administration paradigm in rats to determine how flavorants influence self-administration behavior. By combining i.o. flavorant delivery with fast scan cyclic voltammetry (FSCV) or i.v. nicotine self-administration in adult, male rats, we examined whether flavors alter phasic dopamine (DA) signaling and nicotine self-administration. Oral administration of 10% sucrose or 0.32% saccharin, but not 0.005% menthol, increased phasic DA release in the nucleus accumbens (NAc). Oral sucrose or saccharin, when combined with i.v. nicotine delivery, also led to increased self-administration behavior. Specifically, combined i.o. sucrose and i.v. nicotine decreased responding compared to sucrose alone, and increased responding compared to nicotine alone. In contrast, i.o. flavorants did not alter motivational breakpoint in a progressive ratio task. Oral menthol, which did not alter i.v. nicotine administration, reversed oral nicotine aversion (50 and 100 mg/L) in a two-bottle choice test. Here, we demonstrate that i.o. appetitive flavorants that increase phasic DA signaling also increase self-administration behavior when combined with i.v. nicotine delivery. Additionally, oral menthol effects were specific to oral nicotine, and were not observed with i.v. nicotine-mediated reinforcement. Together, these preclinical findings have important implications regarding menthol and sweet flavorant additive effects on tobacco product use and can be used to inform policy decisions on tobacco product flavorant regulation.
Abstract 14200: Iron Accumulation in the Mitochondria, but not Other Cellular Compartments, Mediates Cardiotoxic Effects of Doxorubicin

Background: Doxorubicin (DOX) is an effective anticancer drug with a side-effect of severe but mechanistically uncharacterized cardiotoxicity. Here, we report that toxic effects of DOX result from iron accumulation specifically inside the mitochondria, and that reduction in mitochondrial iron through facilitation of export or pharmacologic chelation protects the heart against DOX damage. Results: DOX treatment of neonatal rat cardiomyocytes (NRCM) and wild-type (WT) mice significantly increased mitochondrial iron levels, while nuclear and cytosolic iron content remained unchanged. Moreover, mitochondrial, but not cytosolic, iron levels were significantly elevated in the hearts of human patients with DOX cardiomyopathy compared to non-myopathic hearts or hearts with other causes of cardiomyopathy. To test if mitochondrial iron accumulation is the cause for DOX cardiotoxicity, we took genetic and pharmacologic approaches. Reduction in mitochondrial iron levels through genetic overexpression of ATP-binding cassette B8 (ABCB8), a protein that facilitates mitochondrial iron export, was protective against DOX toxicity in vitro and in vivo. Importantly, non-transgenic (NTG) mice displayed significant decrease in cardiac systolic function, disruption of mitochondrial morphology, increased tissue lipid peroxidation (a marker of oxidative stress), and higher mortality rates after DOX treatment, while these parameters were preserved in DOX-treated ABCB8 TG littermates. For the pharmacologic approach, we showed that deferoxamine (DFO), a strong iron chelator, reduced nuclear and cytosolic, but not mitochondrial iron levels, while dexrazoxane (DXZ), the only FDA approved drug for DOX-mediated cardiotoxicity that has mild iron chelator properties, preferentially reduced mitochondrial iron with little to no effect on iron in other cellular compartments. Consistently, we showed that DFO conferred no protection against DOX toxicity in WT mice, while DXZ significantly attenuated DOX-induced damage to the heart. Conclusions: We establish that cardiotoxic effects of DOX are mediated by preferential iron accumulation in the mitochondria, and that targeted reduction in mitochondrial iron protects against DOX-induced cardiomyopathy.
Back to the Basics of Grammar and Style

Part 1 of the grammar and style series: nouns, specifically pluralization, possessives, noun chains, and nominalization.
Avascularity of the Cornea

The absence of blood and lymphatic vessels in the cornea is required for optical clarity and optimal ocular performance. Avascularity is also critical for corneal immune privilege. In this article, the molecular mechanisms supporting corneal avascularity, some of the common ocular disorders associated with the loss of avascularity as well as its clinical implications are discussed. The current understanding and the need for improved comprehension of the relative contribution of hem- and lymph-angiogenesis to corneal immune privilege are also presented. Finally, the role of the cornea as an angiogenesis study platform due to its avascular disposition is highlighted.
Physics-Based-Adaptive Plasma Model for High-Fidelity Numerical Simulations

A physics-based-adaptive plasma model and an appropriate computational algorithm are developed to numerically simulate plasma phenomena in high fidelity. %The physics-based-adaptive plasma model is dynamically refined based on the local conditions to provide uniform model fidelity throughout the domain at all times of the simulation. The physics-based-adaptive plasma model can be dynamically refined based on the local plasma conditions to increase model fidelity uniformity throughout the domain at all times of the simulation. %The adaptive plasma model uses continuum representations of the plasma, which include a kinetic Boltzmann model for the highest fidelity, multi-fluid plasma models (13N-moment and 5$N$-moment), and single-fluid MHD models for the lowest fidelity. The adaptive plasma model uses continuum representations of the plasma, which include a kinetic Vlasov model for the highest fidelity, multi-fluid 5$N$-moment plasma model, and single-fluid MHD model for the lowest fidelity. The models include evolution equations for the electromagnetic fields, electron species, ion species, and neutral species. A nodal discontinuous Galerkin finite element method is implemented and is coupled with various implicit and explicit Runge-Kutta methods. Various model coupling techniques are investigated for a 5$N$-moment multi-fluid models with a Vlasov-Maxwell model, and a 5$N$-moment two-fluid model with an MHD model. Continuum plasma models using consistent normalizations and identical spatial representations provide straightforward and accurate coupling between the models. %The solution approach offers the potential for high-order accuracy and computational efficiency. The solution approach offers high-order accuracy and computational efficiency. Target compute platforms are heterogeneous computer architectures using a compute model that minimizes data movement.
Ranking critical activities in process architectures

Abstract Identification of important activities in a process architecture is a complex task. This paper takes a network perspective approach: Process architectures are represented as activity networks and are modelled as a Discrete-Time Markov Chain (DTMC). Here we propose a DTMC-based component ranking method (Markov chain) to rank important activities in a variety of process architectures of complex system development projects. Analysis of the results show that the proposed model possesses the capability to highly rank critical activities in a process architecture that are capable of either leading to task volatility i.e. increase the probability of rework, have the tendency to cause large iteration cycles, posing a high risk to the process in terms of delay and failure, or leading to unplanned rework. The results are also compared with other widely used network metrics, namely, closeness, betweenness and eigenvector centrality. In our pilot study on four different process architectures, Markov chain outperformed other ranking strategies in highly ranking the significant activities of the process architecture.
Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies

Mouse models of the human porphyrias have proven useful for investigations of disease pathogenesis and to facilitate the development of new therapeutic approaches. To date, mouse models have been generated for all major porphyrias, with the exception of X-linked protoporphyria (XLP) and the ultra rare 5-aminolevulinic acid dehydratase deficient porphyria (ADP). Mouse models have been generated for the three autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). The AIP mice, in particular, provide a useful investigative model as they have been shown to have acute biochemical attacks when induced with the prototypic porphyrinogenic drug, phenobarbital. In addition to providing important insights into the disease pathogenesis of the neurological impairment in AIP, these mice have been valuable for preclinical evaluation of liver-targeted gene therapy and RNAi-mediated approaches. Mice with severe HMBS deficiency, which clinically and biochemically mimic the early-onset homozygous dominant AIP (HD-AIP) patients, have been generated and were used to elucidate the striking phenotypic differences between AIP and HD-AIP. Mice modeling the hepatocutaneous porphyria, porphyria cutanea tarda (PCT), made possible the identification of the iron-dependent inhibitory mechanism of uroporphyrinogen decarboxylase (UROD) that leads to symptomatic PCT. Mouse models for the two autosomal recessive erythropoietic porphyrias, congenital erythropoietic porphyria (CEP) and erythropoeitic protoporphyria (EPP), recapitulate many of the clinical and biochemical features of the severe human diseases and have been particularly useful for evaluation of bone marrow transplantation and hematopoietic stem cell (HSC)-based gene therapy approaches. The EPP mice have also provided valuable insights into the underlying pathogenesis of EPP-induced liver damage and anemia.
Covalent Heterobivalent Inhibitor Design for Inhibition of IgE-Dependent Penicillin Allergy in a Murine Model

Drug allergies occur when hapten-like drug metabolites conjugated to serum proteins, through their interactions with specific IgE, trigger allergic reactions that can be life threatening. A molecule termed covalent heterobivalent inhibitor (cHBI) was designed to specifically target drug hapten-specific IgE to prevent it from binding drug-haptenated serum proteins. cHBI binds the two independent sites on a drug hapten-specific Ab and covalently conjugates only to the specific IgE, permanently inhibiting it. The cHBI design was evaluated via ELISA to measure cHBI-IgE binding, degranulation assays of rat basophil leukemia cells for in vitro efficacy, and mouse models of ear swelling and systemic anaphylaxis responses for in vivo efficacy. The cHBI design was evaluated using two separate models: one specific to inhibit penicillin G-reactive IgE and another to inhibit IgE specific to a model compound, dansyl. We show that cHBI conjugated specifically to its target Ab and inhibited degranulation in cellular degranulation assays using rat basophil leukemia cells. Furthermore, cHBIs demonstrated in vivo inhibition of allergic responses in both murine models. We establish the cHBI design to be a versatile platform for inhibiting hapten/IgE interactions, which can potentially be applied to inhibit IgE-mediated allergic reactions to any drug/small-molecule allergy.
Long-Term Behavior of Neural Networks

Two important interdisciplinary goals to which statistical physics can potentially make vital contributions are (a) the formulation of dynamical models which capture the primary features of information processing and adaptive behavior in living nervous systems and (b) the design of computational algorithms or devices which solve cognitive problems according to the principles of natural intelligence. Currently, both goals are being actively pursued in terms of neural networks.l–10 A neural network consists of a collection of neuron-like units, with synapse-like couplings which may be adjusted according to some learning rule, so as to achieve the desired performance of the network. The equation of motion determining the state of the network at each time is nonlinear and dissipative. Generally, the long-term behavior of such networks is considered to determine their usefulness in both the natural and artificial contexts: it is generally identified with the response of the organism to a given initial stimulus, or else as the solution provided by the algorithm or device. The essential idea is exemplified by an idealized form of content-addressable memory (CAM) discussed by Hopfield, based on fully and symmetrically connected nets of binary neurons governed by an asynchronous threshold dynamics.11 Started from any initial state, the system evolves necessarily to some stable fixed-point configuration. The end point of the evolution is identified with the stored memory with which the stimulus represented by the initial state is associated. Such a memory is distributed, in the sense that information about it is widely distributed over many synapses (couplings) in the system; it is error correcting in that a few errors in the input will not disturb accurate recall of the relevant stored memory.
A multi-object spectrograph using single-mode fibers with a coronagraph: progress towards laboratory results on the high-contrast testbed for segmented telescopes

Using single-mode fibers (SMFs) in the image plane of coronagraphs allows access to a new wavefront control regime. By using deformable mirrors to create a mismatch between the incoming starlight and the fiber mode, SMFs can serve as integral parts of the light suppression ability of the coronagraph. Previous promising simulation results show increased spectral bandwidth and throughput when using SMFs in a multi-object role, and previous laboratory results have shown increased light suppression using a single SMF. We present an update on efforts to combine a multi-core SMF with a high-resolution spectrograph on the High Contrast Testbed for Segmented Telescopes (HCST) at Caltech. We present our planned experimental design, as well as simulations of expected performance when controlling multiple fiber cores on HCST. We will test the potential increase in spectral bandpass and throughput resulting from the switch to SMFs, as well as the stability of the wavefront control solution.
Transgressive Mexicana sexualities and the promise of progress

Latin American and Latina women's sexualities have often been represented, and theorized, along the terms of sexual morality, restraint and emancipation. In this article, I explore how sexual norms...
Modeling, optimization, and control of ship energy systems using exergy methods

Abstract Changing emissions regulations, fuel price fluctuations and development of new energy-intensive mission systems are driving both component technological innovation and require more sophisticated controls on-board modern ships. Historically, numerous components and systems aboard ships perform energy conversions from one form to another. Conversion from chemical to thermal to kinetic to electrical and back to thermal energy are common. Today, subsystems are designed separately without opportunity for optimizing overall system-of-systems performance. By modeling multiple system domains simultaneously and applying the Second Law of Thermodynamics, this progresses towards overall ship system optimization. Exergy, the available energy for performing useful work, and exergy destruction was calculated in each energy conversion process. Knowledge of the exergy flows leads to a system-of-systems optimization to minimize overall exergy destruction translating into lower emissions and fuel costs. This can eventually result in more efficient, smaller and lighter shipboard systems. A model of notional shipboard power and cooling system is presented that features a pulsed load (an electromagnetic railgun) and have implemented both traditional and exergy-based control schemes. This paper will briefly review the modeling, which has been previously published, and present results using exergy destruction for optimization of the ship system controls.
Hippo Signaling: Autophagy Waits in the Wings.

Crosstalk between signaling networks can help coordinate diverse cellular functions. In this issue of Developmental Cell, Tyra et al. identify connections between the cell-growth-promoting transcription factor YAP/Yorkie and the autophagy-regulating kinase Ulk1/Atg1.
A Reading of the Third “Vespers” by Louise Glück

This paper presents a reading of the third “Vespers,” a poem by Louise Gluck collected in The Wild Iris , a book of poem sequence spoken by four different voices, dealing with the fact of human existence in the world, especially in terms of human existential suffering. To this date, this award-winning book has been considered by many to be among the poet’s greatest achievements. This being the case, there have been so few detailed readings of the 54 poems constituting the book, however. Most of the existing scholarships on the poems are topic-centered rather than poem-centered. This article attempts to make its contribution to this by presenting a close reading of one of the poems, which is especially central to this polyphonic book both thematically and structurally. Assuming the critical premises and the analytical procedure of Helen Vendler, whose focus is on a poem’s intrinsic elements and its relations to its thematic features, the paper discusses the third “Vespers”’s theme as expressed by both its obvious and minute features. By analyzing the poem’s title, body, internal structure, diction, tense, mechanic, rhythm, syntax, and imagery, the paper concludes that the poem expresses and dramatizes, through the obvious and minute details, the perennial theme of human’s pining for explanation about his/her discontent, which in the cosmos of the poem is directed to God, and its attendant feelings of doubt and conviction as a result of having to come up with his/her own answer as the one who holds the definite answer stays silent.
Chapter 2 – Linear Algebra

Publisher Summary The chapter provides an overview of linear algebra, also called matrix theory. An important tool in many areas of scientific computing is linear algebra. An important type of matrix is nonsingular. The symmetric matrices also play a central role in scientific computing. In general, it is difficult to check whether a given matrix is nonsingular. However, one exception is triangular matrices. A triangular matrix is nonsingular if and only if all its main diagonal elements are nonzero. Another important class of nonsingular matrices are those that are orthogonal.
Electromagnetic Spectrum of Am 241

The electromagnetic spectrum of ${\mathrm{Am}}^{241}$ has been studied with a ten-inch bent-crystal spectrometer and a sodium iodide scintillation counter. Twelve gamma rays, sixteen Np $L$ x-rays, and eight Am $L$ x-rays have been measured. The gamma rays in Np have energies of 26.363, 33.199, 43.463, 59.568, 103, 113, 130, 159, 210, 270, 328, and 370 kev. The x-ray energies establish the validity of the Mosley extrapolations in this region of the periodic table. Details of the spectrometer operation and calibration are given.
A Note on the Use of Divergence Boundary Conditions in CEM

In this brief note we wish to point out that using a divergence boundary condition in the manner suggested in the previous paper [1] may lead to the appearance of spurious solutions (although of another kind from that referred to in the titles of [1]–[2]). This is because second order wave equations with interior divergence constraints and second order wave equations with divergence boundary conditions are not always equivalent. Discretizations (including least squares) which do not take this into account can converge to incorrect solutions. These facts are proved in our forthcoming paper [3] where a detailed account of the connection between the problems is given. Here we will simply give an example from our paper which shows that the formulations are not equivalent; we will also state a positive result about the equivalence of the formulations.
Therapist-Observer Concordance in Ratings of EBP Strategy Delivery: Challenges and Targeted Directions in Pursuing Pragmatic Measurement in Children’s Mental Health Services

Pragmatic measures of therapist delivery of evidence-based practice (EBP) are critical to assessing the impact of large-scale, multiple EBP implementation efforts. As an initial step in the development of pragmatic measurement, the current study examined the concordance between therapist and observer ratings of items assessing delivery of EBP strategies considered essential for common child EBP targets. Possible EBP-, session-, and therapist-levels factors associated with concordance were also explored. Therapists and independent observers rated the extensiveness of therapist (n = 103) EBP strategy delivery in 680 community psychotherapy sessions in which six EBPs were used. Concordance between therapist- and observer-report of the extensiveness of therapist EBP strategy use was at least fair (ICC ≥ .40) for approximately half of the items. Greater therapist-observer concordance was observed in sessions where a structured EBP was delivered and in sessions where therapists reported being able to carry out planned activities. Findings highlighted conditions that may improve or hinder therapists' ability to report on their own EBP strategy delivery in a way that is consistent with independent observers. These results can help inform the development of pragmatic therapist-report measures of EBP strategy delivery and implementation efforts more broadly.
Multi-User Virtual Environments (MUVEs) as Alternative Lifeworlds: Transformative Learning in Cyberspace:

Direct instruction (PowerPoint presentations, lectures) often imposes hierarchical classroom structures where the teachers are considered experts, imparting knowledge to passive learners. However, ...
Must Penal Law Be Insulated from Public Influence

Punishment and democracy appear to exacerbate each other’s worst features. The institutions and moral intuitions used to punish those that break the law can hollow out civic participation, distort the electorate, and undermine core democratic values. Likewise, many have argued the decentralized character of democracy is a key, albeit indirect, cause of increasingly punitive public policies that are divorced from any reasonable penological purpose. Given the effects of electoral politics, many have called for the separation, or general insulation, of state punishment from public influence. However, recent empirical work on punitive attitudes and institutional design has begun to chip away at this common sense. This article contextualizes and qualifies the various mechanisms of policy feedback and public opinion formation thought by political theorists to undermine democratic participation in penal institutions and makes a normative case that insulating the public from penal law actively sustains injustice.
Blastocyst score, a blastocyst quality ranking tool, is a predictor of blastocyst ploidy and implantation potential.

Objective To convert blastocyst (BL) morphological grade and BL day into a numeric blastocyst score (BS). Design Retrospective cohort study. Setting Academic center. Patient(s) A total of 5,653 BL of known implantation (fetal heart, FH) and 11,348 biopsied BL. Intervention(s) Based on their FH rates and/or significance, a score (1–4) was assigned to each BL grade component. The BL morphological score (BMS) is the sum (BS = BMS on day 5; BS = BMS + 2 on day 6). Main Outcome Measure(s) Statistics characterized the FH and euploidy odds with BS. Result(s) All three morphology grade components and BL day were associated with implantation and euploidy probability. The FH rate and euploidy odds decrease with larger BS. The BS was the most important factor (odds ratio [OR] per unit change = 0.807, 95% confidence interval [CI] 0.784, 0.831) for untested and euploid BL implantation, and the sole one for euploid BL (OR/unit change = 0.845, 95% CI 0.803, 0.889). The BS is the second most significant factor after maternal age for euploidy probability (OR/unit change = 0.808, 95% CI 0.795, 0.822). In training and validation sets (75:25), the BS can predict implantation with similar area under the curve [AUC] (training = 0.628, 95% CI 0.613, 0.643; validation = 0.606, 95% CI 0.581, 0.631). The BS has better euploidy prediction ability (training AUC = 0.683, 95% CI 0.673, 0.693; validation AUC = 0.698, 95% CI 0.681, 0.715). The BS can stratify BL into good (3–5), fair (6–9), and poor (10–14) groups, reflecting their FH, live birth rates, and ploidy status. Advanced maternal age was associated with lower untested BL implantation and lower euploidy odds across all groups. Conclusion(s) The BS is a predictor of BL ploidy and FH implantation.
The importance of acquisition learning on nicotine and varenicline drug substitution in a drug-discriminated goal-tracking task.

Abstract Nicotine and varenicline (Chantix®; the leading non-nicotine cessation pharmacotherapy) can come to control appetitive behaviors such as goal-tracking. We tested rats (N = 48) in a drug-discriminated goal-tracking (DGT) task where each rat received daily subcutaneous injections of either nicotine (0.4 mg/kg) or saline (0.9% [w/v]) interspersed across the acquisition phase (Phase 1). On saline days, sucrose was intermittently available. On nicotine days, sucrose was withheld. All rats acquired the discrimination with increased goal-tracking rates on saline days relative to nicotine days. Following acquisition, rats were separated into four groups to assess drug-substitution and discrimination reversal in Phase 2. The first group maintained the stimulus-reinforcer relation from acquisition (NIC-). The reversal group was now given access to sucrose on nicotine days (NIC+). The substitution group replaced nicotine with varenicline (1 mg/kg) while maintaining the acquisition stimulus-reinforcer relation (VAR-). The substitution and reversal group had nicotine replaced by varenicline and the stimulus-reinforcer relation reversed (VAR+). Rats in all groups learned or maintained their Phase 1 discriminations. For Phase 2, the reversal groups (+ conditions) acquired their discriminations within 10 sessions. The VAR- group displayed a pattern of disrupted discrimination at the outset of Phase 2 but was reestablished after continued training. In substitution testing, VAR groups received nicotine and NIC groups received varenicline. The NIC- and VAR- groups displayed full substitution of the test stimulus whereas the NIC+ and VAR+ groups displayed partial substitution of the test stimulus. Rats underwent nicotine extinction in Phase 3. Initial responding for each group mimicked Phase 2 training (i.e., higher responding by the reversal groups). All rats maintained similarly low levels of responding after six sessions. In conclusion, initial learning history with nicotine (i.e., + or −) influenced drug-stimulus substitution and the rate at which new learning (e.g., reversal) occurs with the varenicline and nicotine interoceptive stimuli.
Differential and Integral Cross Sections for the Electron-Impact Excitation of the a Δ g 1 and b Σ g + 1 States of O 2

Electron-impact energy-loss spectra of ${\mathrm{O}}_{2}$ have been analyzed for incident electron energies from 4 to 45 eV, scattering angles from 10\ifmmode^\circ\else\textdegree\fi{} to 90\ifmmode^\circ\else\textdegree\fi{}, and energy losses from 0 to 5 eV. The inelastic processes observed were the excitation of the $a^{1}\ensuremath{\Delta}_{g}$ and $b^{1}\ensuremath{\Sigma}_{g}^{+}$ electronic states and vibrational excitation in some cases to ${v}^{\ensuremath{'}\ensuremath{'}}=13$. The excitation cross sections at each energy were made absolute by normalizing the sum of the integral cross sections (all inelastic, ionization, and elastic) to measured electron-${\mathrm{O}}_{2}$ total cross sections. The differential cross sections for the $a^{1}\ensuremath{\Delta}_{g}$ and $b^{1}\ensuremath{\Sigma}_{g}^{+}$ states show nearly isotropic behavior, as expected for optically spin-for-bidden transitions. The elastic differential cross sections are strongly forward peaked at higher energies, but become only slightly forward peaked at the lower energies. The integral cross sections for the excitation of the $a^{1}\ensuremath{\Delta}_{g}$ and $b^{1}\ensuremath{\Sigma}_{g}^{+}$ states reach their maxima near 7 eV and are more than an order of magnitude larger than previous estimates. The integral elastic cross section reaches its maximum at around 10 eV.
Posverdad como repertorio de acción: Disputa discursiva de la ultraderecha chilena en Facebook

This article shows how the communities of the national extreme right produce and organize post-truth through political speeches on Facebook. It is proposed to analyze the ways in which the Chilean extreme right uses post-truth as part of its repertoire of political action for discursive production. For this, these productions are identified, the internal components of post-truth present there are systematized and it is characterized how the ultra-right communities articulate the components to produce political discourses through post-truth. In the first place, the concept is theoretically reviewed based on its historical development and incidence in communication and current politics, to later incorporate the traditional and contextualized, globally and regionally, far-right views. Thus, through a qualitative approach channeled into a virtual ethnography, the Discourse-Cognition-Society triangulation of critical discourse analysis is articulated, showing how these communities take advantage of the little control that exists on the Internet through subliminal and appellative communication strategies, influencing digital public opinion and establishing an intentional act that takes advantage of the organizational potential that Facebook offers.
A New Wave of Research on Civilizational Politics

A new wave of scholarship has made major advances in how we understand the politics of civilizational identity by drawing powerfully from conceptual tools developed over the years to study other forms of identity. What unites this wave is treating civilizations not as distinctive “things” that might “clash” but as meaningful social imaginings. This growing body of work is far from monolithic, generating alternative theories that should structure scholarly debate going forward. Central issues include whether civilizational identity is primarily elite led or mass driven, whether it inherently involves conflictual human impulses, what the role of religion and values are in driving it, what its relationship is to nationalism, and how similarly we can expect the countries and people who share civilizational identity to behave. We also find emerging debates on what this newly conceptualized civilizational identity explains in contemporary world politics. Social scientists are now only beginning to apply important tools of social science to this question, with even public opinion research in its infancy. Early findings suggest civilizational identity may be shaping not only elite foreign policy making but also patterns of domestic politics, including the recent rise of populism and levels of democracy and authoritarianism more generally.
5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium

5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of Escherichia coli, which could be ameliorated by treatment with 5-ASA. However, 5-ASA was no longer able to reduce inflammation, restore epithelial hypoxia, or blunt an expansion of E. coli in DSS-treated mice that lacked Pparg expression specifically in the intestinal epithelium. These data suggest that the anti-inflammatory activity of 5-ASA requires activation of epithelial PPAR-γ signaling, thus pointing to the intestinal epithelium as a potential target for therapeutic intervention in ulcerative colitis.IMPORTANCE An expansion of Enterobacterales in the fecal microbiota is a microbial signature of dysbiosis that is linked to many noncommunicable diseases, including ulcerative colitis. Here, we used Escherichia coli, a representative of the Enterobacterales, to show that its dysbiotic expansion during colitis can be remediated by modulating host epithelial metabolism. Dextran sulfate sodium (DSS)-induced colitis reduced mitochondrial activity in the colonic epithelium, thereby increasing the amount of oxygen available to fuel an E. coli expansion through aerobic respiration. Activation of epithelial peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling with 5-aminosalicylic acid (5-ASA) was sufficient to restore mitochondrial activity and blunt a dysbiotic E. coli expansion. These data identify the host's epithelial metabolism as a potential treatment target to remediate microbial signatures of dysbiosis, such as a dysbiotic E. coli expansion in the fecal microbiota.
Time-Series Analyses of Water-Quality Data

The basic concepts of Fourier and power spectrum analyses are presented in terms of their application to dissolved oxygen and temperature data of the Delaware Estuary. The results of Fourier analyses computations performed on hourly data from water-quality monitoring stations are presented. For temperature, more than 92% of the total variance is accounted for by the 365-day periodicity. For dissolved oxygen, more than 90% of the total variance is accounted for by the annual periodicity and the next four higher harmonics (semi-annual; tri-annual, etc.). The dissolved oxygen variability remaining after removal of the principal Fourier components was found to be approximately normally distributed with an average standard deviation of 0.85 mg per 1. Power spectrum analyses of the 24-hr averaged DO residual seconds indicated a peak in the region of 30 days to 60 days and for temperature a peak is dominant at 30 days. The analyses all indicate a predominance of low frequency (periods of from 7 days to 1 yr and longer) types of phenomena. The implications of the results from a sampling and control point of view are evaluated.
Bimanual skill development in pediatric below-elbow amputation: A multicenter, cross-sectional study

The purpose of this study was to investigate the following in children with unilateral below-elbow amputation: (1) development of bimanual functional skills, (2) development patterns relative to able-bodied children, and (3) the relationship between duration of prosthetic wear and bimanual functional performance. Sixty-nine children with unilateral below-elbow amputation, all less than ten years old, were assessed on 14 prosthesis-assisted bimanual ADL, including play, feeding, dressing, and hygiene activities, which have been studied previously in able-bodied children. Bimanual ADL skill development was not delayed in five of the 14 comparisons to previously published standards, but most development patterns had multimodal, nonmonotonic performance profiles. Duration of prosthetic wear and other factors previously believed to contribute to good prosthetic function were not well correlated to ADL skills (r less than .52). Although these children had no CNS dysfunction, it is apparent that below-elbow amputation impedes pediatric ADL skill development. The cause of these delays appears to be complex and is not expressed uniformly among all children; thus, the delays observed are not simply due to mechanical deficiencies of the prosthetic restoration.
Singularity analysis of fully-constrained cable-driven parallel robots with seven cables

Singularity analysis of parallel robots is an important issue. A parallel robot could be out of control or crash in a singular configuration. The unidirectional constraint of cables makes the singularity analysis of cable-driven parallel robots different from that of rigid-link parallel robots even if they have similar kinematical architectures. This paper discusses various categories of singularities of fully-constrained cable-driven parallel robots. Based on their natures, singularities of cable-driven parallel robots are classified into two categories: the Jacobian singularity and the force-closure singularity. A Jacobian singularity occurs when the Jacobian matrix of a cable-driven parallel robot loses its full rank. When the Jacobian matrix of a cable-driven parallel robot has a full rank, the cables' inability to generate tension will lead to force-closure singularities, which can always happen to fully-constrained cable-driven parallel robots. An algorithm of identifying force-closure singularities of fully-constrained cable-driven parallel robots with seven cables is proposed. Understanding of the natures of singularities is important for the design and control of cable-driven parallel robots.
Terror Management Theory

Terror management theory (TMT) is a social psychological theory of attitudinal and behavioral responses to humans' awareness of their mortality (Greenberg, Pyszczynski, & Solomon, 1986; Solomon, Greenberg, & Pyszczynski, 1991). The theory posits that possessing an awareness of one's own inescapable death creates a uniquely human psychological problem, consequently impacting myriad attitudes and behaviors. Although there are many potential causes of anxiety in the world, the theory suggests that this existential concern differs from other anxiety-provoking events or thoughts in that it is absolutely certain to occur and ultimately entails the end to all other human motives. This makes the management of death-related psychological terror an especially important task for maintaining psychological equanimity. Keywords: cultural worldview; mortality salience; self-esteem; terror management theory
Sensitivity of internal tide generation in Hawaii

Energy from the barotropic tide is transferred into the baroclinic tide over topographic gradients, which provides a mechanism for the ocean boundaries to communicate with the deep ocean, to close energy budgets, and as a source of flux affecting nutrient supply and larval transport. Understanding the temporal variability of the conversion from barotropic to baroclinic tides is critical to our understanding of these processes. Using a numerical model and its adjoint, we examine the sensitivity of tidal conversion at Kaena Ridge in Hawaii. We find a sensitivity to changes in the upper ocean due to a phase difference between the pressure anomaly and tidal velocity caused by internal waves generated on the opposite slope of the ridge; however, we also find that conversion is equally as sensitive to local, deep stratification changes.
Providers’ Experiences with a Melanoma Web-Based Course: a Discussion on Barriers and Intentions

Primary care visits provide an opportunity for skin examinations with the potential to reduce melanoma mortality. The INFORMED (INternet curriculum FOR Melanoma Early Detection) Group developed a Web-based curriculum to improve primary care providers' (PCPs') skin cancer detection skills. This study details feedback obtained from participant focus groups, including the feasibility of implementing in other PCP practices. Practicing PCPs at Henry Ford Health System and Kaiser Permanente Northern California completed the curriculum. Feedback sessions were conducted with standardized questions focusing on four domains: (1) overall impressions of the curriculum, (2) recommendations for improvement, (3) current skin examination practices, and (4) suggestions for increasing skin screening by PCPs. Discussions at each site were audio recorded, transcribed verbatim, and de-identified. Providers (N = 54) had a positive impression of the Web-based curriculum, with suggestions to provide offline teaching aids and request assistance. Despite having improved confidence in diagnosing malignant lesions, many providers felt a lack of confidence in performing the screening and time constraints affected their current practices, as did institutional constraints. Providers intended to increase discussion with patients about skin cancer. The accessibility, effectiveness, and popularity of the curriculum indicate potential for implementation in the primary care setting. Participating providers noted that institutional barriers remain which must be addressed for successful dissemination and implementation.
A fuzzy approach to pose determination in object recognition

Object recognition is the process of identifying and locating known objects in complex images. It includes extracting relevant features, grouping these features together, selecting an appropriate object model, and determining the pose (position and orientation) of the object in the scene. In earlier work, the author has shown that fuzzy methods are appropriate for representing geometric relationships that are used for both perceptual grouping of geometric features and for associating geometric image features with models. The paper explores fuzzy methods for the final step in object recognition, that of global pose determination. She develops a method based on fuzzy c means (FCM) clustering, and demonstrates its effectiveness over traditional crisp pose clustering.
Partial placenta accreta in pregnancies following chemotherapy for gestational trophoblastic neoplasms.

Abstract Women given chemotherapy for gestational trophoblastic neoplasms had an increased incidence of partial placenta accreta in subsequent pregnancies. Conservative methods of management of the retained placenta, preserving reproductive capacity in these women, were not associated with maternal morbidity or deaths.