Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Dasatinib and Its Structural Analogs as CYP3A4 Mechanism-Based Inactivators and the Proposed Bioactivation Pathways

Dasatinib was approved in 2006 for the treatment of imatinib-resistant chronic myelogenous leukemia and functions primarily through the inhibition of BCR-ABL and Src kinase. Dasatinib is extensively metabolized in humans by CYP3A4. In this study, we report that the bioactivation of dasatinib by CYP3A4 proceeds through a reactive intermediate that leads to CYP3A4 inactivation with KI = 6.3 μM and kinact = 0.034 min–1. The major mechanism of inactivation proceeds through hydroxylation at the para-position of the 2-chloro-6-methylphenyl ring followed by further oxidation, forming a reactive quinone-imine, similar to the reactive intermediates formed by acetaminophen and diclofenac. Formation of a reactive imine-methide was also detected but appears to be a minor pathway. When glutathione was added to human liver microsomal incubations, dasatinib-glutathione adducts were detected. Numerous dasatinib analogs were synthesized in an effort to understand what modifications would block the formation of reactive intermediates during dasatinib metabolism. It is interesting to note that blocking the site of hydroxylation with a methyl group was not effective because a reactive imine-methide was formed, nor was blocking the site with fluorine because the fluorine was removed through an oxidative defluorination mechanism and the reactive quinone-imine was still formed. Numerous analogs are presented that did effectively block the formation of glutathione adducts and prevent the inactivation of CYP3A4.
Intraoperative Plateletpheresis and Autologous Platelet Gel Do Not Reduce Chest Tube Drainage or Allogeneic Blood Transfusion After Reoperative Coronary Artery Bypass Graft

Platelet-rich plasma (PRP) is postulated to decrease postoperative mediastinal chest tube drainage (MCTD) and allogeneic blood transfusions (ABT) after surgery with cardiopulmonary bypass. However, recent metaanalysis of the literature reveals that few good quality (therapeutic yield) trials that show a benefit have been published. The potential hemodynamic instability caused by plateletpheresis has not been emphasized. We studied the effect of plateletpheresis on MCTD, ABT, and hemodynamic stability in reoperative coronary artery bypass graft patients, a group perceived to be at high risk for ABT. Ninety patients were randomly assigned to Pheresis or Control groups. &egr;-Aminocaproic acid was given to all patients. Hemodynamic instability was assessed by degree of volume and inotrope resuscitation required. Part of the sequestered platelet volume was used to make autologous platelet gel, which was applied as a wound sealant. Mean pheresis yield was 30% ± 7% of the circulating platelet mass or 6.4 ± 2.2 allogeneic platelet unit equivalents. Total MCTD did not differ between the groups. There were no differences in mean packed red blood cell, platelet, and plasma transfusion rates. Overall, 52% of the Pheresis group received ABT, versus 55% of the Control group. Fifty-three percent of the Pheresis group patients exhibited significant hemodynamic instability, versus 27% of the Control group (P < 0.05). This study was unable to show any reduction in MCTD or ABT, although the plateletpheresis technique may offset platelet dysfunction caused by aspirin or increased blood exposure to nonbiologic surfaces, or it may compensate for lack of antifibrinolytic use. The significantly increased incidence of hemodynamic instability in the Pheresis group means that the risk/benefit ratio must be determined for individual cardiac surgical units.
"Mrs. Landes Meet Mrs. Benedict": Culture Pattern and Individual Agency in the 1930s

This article presents Ruth Landes as a transitional figure in 20th-century anthropology between the culture and personality studies of the interwar years and the study of power and structural dynamics so important in the discipline by the end of the century. Expanding on Benedict's theory of culture pattern and employing the life history method, Landes highlights in her work relations of power in the structural dynamics of culture as she explores: the experience of social marginality; the making of the public symbolic order; the plurality of local knowledge systems; the role of the individual; what she called "the moot problem of women and men"; and the relationship of researcher and researched. [Keywords: Ruth Landes, Ruth Benedict, culture, gender, power]
Parametric yield management for 3D ICs: Models and strategies for improvement

Three-Dimensional (3D) Integrated Circuits (ICs) that integrate die with Through-Silicon Vias (TSVs) promise to continue system and functionality scaling beyond the traditional geometric 2D device scaling. 3D integration also improves the performance of ICs by reducing the communication time between different chip components through the use of short TSV-based vertical wires. This reduction is particularly attractive in processors where it is desirable to reduce the access time between the main logic die and the L2 cache or the main memory die. Process variations in 2D ICs lead to a drop in parametric yield (as measured by speed, leakage and sales profits), which forces manufacturers to speed bin their chips and to sell slow chips at reduced prices. In this paper we develop a model to quantify the impact of process variations on the parametric yield of 3D ICs, and then we propose a number of integration strategies that use a graph-theoretic framework to maximize the performance, parametric yield and profits of 3D ICs. Comparing our proposed strategies to current yield-oblivious methods, it is demonstrated that it is possible to increase the number of 3D ICs in the fastest speed bins by almost 2×, while simultaneously reducing the number of slow ICs by 29.4%. This leads to an improvement in performance by up to 6.45% and an increase of about 12.48% in total sales revenue using up-to-date market price models.
Detection of Delirium by Bedside Nurses Using the Confusion Assessment Method

A prospective, descriptive study was used to assess the diagnostic validity of the Confusion Assessment Method (CAM) administered at the bedside by nurses in daily practice. Two different scoring methods of the CAM (the specific (SPEC) and sensitive (SENS) methods) were compared with a criterion standard (CAM completed by trained research nurses). During a 5‐month period, all patients consecutively admitted to an acute geriatric ward of the University Hospitals of Leuven (Belgium) were enrolled in the study. The 258 elderly inpatients who were included underwent 641 paired but independent ratings of delirium by bedside and trained research nurses.
Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15–30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25–200 μg/mL) and up to three hours of exposure, whereas at higher concentrations (300–500 μg/mL) and prolonged (six hours) exposure viability reduced to 55%–65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H2DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration- and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death.
Relational schemas and the processing of social information.

It has long been one of the grand ideas in psychology that people internalize their relationships with significant others, which influences their experience of subsequent relationships and their sense of self. Recent work in social cognition has largely neglected the impact of internally represented interpersonal information, however, with researchers choosing instead to focus on the perception of self and other persons in isolation. After a review of relevant theoretical models, it is proposed that research could profitably examine people's relational schemas, defined as cognitive structures representing regularities in patterns of interpersonal relatedness
Predictor-based model reference adaptive control of an unmanned underwater vehicle

Unmanned Underwater Vehicles (UUVs) are being deployed in advanced applications that require precise manoeuvring close to complex underwater structures such as oilrigs and subsea installations or moving objects such as ships and submarines. The effect of vehicle's hydrodynamic parameter variations is significant in such scenarios and in extreme conditions the UUV may experience loss of control. In addition, external disturbances and actuator failures degrade the performance of the UUV. Adaptive control has been identified as a promising solution that can improve the performance in such situations. However, adaptive control is not widely used in UUVs mainly due to the trade-off between fast learning and smooth control signals. The latter can be guaranteed at low learning rates but require additional input to improve learning. The Predictor Model Reference Adaptive Control (PMRAC) is one such method that uses a prediction error to improve learning. In this paper, the performance of PMRAC in UUV applications is investigated and compared to standard Model Reference Adaptive Control (MRAC) at low learning rates under normal operational conditions, partial actuator failure, and under the influence of external disturbances. Simulation results show that PMRAC significantly reduces the tracking error compared to MRAC. In addition, PMRAC is less affected and recovers quickly from actuator failure and external disturbances, while generating smooth control signals with less oscillation compared to MRAC.
Educational and Career Confidence and Motivation Among Female and Male Undergraduates

Changes in six measures of achievement-related motivation and confidence were tested in a longitudinal study of 138 women and 96 men during their first year at a mid-sized, midwestern public university. An interaction was found between gender and level of course enrollment during the year (p < .05). Full-time college enrollment was advantageous for the men but disadvantageous for the women as measured by the motivation and confidence variables. This interaction could not be explained by initial differences in the confidence and motivation variables or by differences in 18 other noncampus variables tested. An interaction was also found between acceptance of campus advisement and gender (p < .03). Both findings suggest that the men’s achievement-related motivation and confidence increased with greater assimilation into the campus environment, but that the women showed more positive changes when they were less well assimilated. Implications for differences in the campus experiences of men and women are discussed.
Medial temporal structures relate to memory impairment in Alzheimer’s disease: an MRI volumetric study

OBJECTIVES Memory impairment is not only the earliest clinical symptom but a central and prominent feature throughout the course of Alzheimer’s disease. Alzheimer related pathological alterations in the medial temporal structures may account for the memory impairments in patients with Alzheimer’s disease. The aim of this study was to elucidate the role of the medial temporal structures in memory impairment caused by Alzheimer’s disease. METHODS Using high resolution MRI and a semiautomated image analysis technique, volumes of the medial temporal structures (amygdaloid complex, hippocampal formation, subiculum, and parahippocampal gyrus) were measured, and correlations between atrophy of each structure and memory dysfunction in patients with Alzheimer’s disease were examined. RESULTS Patients with Alzheimer’s disease showed poor performance on verbal and non-verbal memory tests, and MRI volumetry showed a significant volume reduction of the medial temporal lobe structures. Volumes of the amygdaloid complex and of the subiculum correlated with memory performance. Stepwise regression analyses disclosed that the volume of the right amygdaloid complex specifically predicted visual memory function and to some extent verbal memory function, and that the volume of the left subiculum specifically predicted verbal memory function. Atrophy of the hippocampus did not predict severity of memory impairment. CONCLUSIONS The presence of perihippocampal damage involving the amygdala proper, its surrounding cortex, and the subiculum further increased the severity of memory impairment attributable to hippocampal damage in Alzheimer’s disease.
Co‐worker trust as a social catalyst for constructive employee attitudes

Research into interpersonal trust within organisational contexts tends to concentrate on managers as a referent, largely ignoring the potential social benefits of trust amongst co‐workers. Hence, the aim of this study is to investigate the influence of co‐worker trust on selected organisational perceptions and attitudes. Results provided empirical support for the fundamental role of co‐worker trust. Co‐worker trust was found to be a significant predictor of perceived organisational support, lowered turnover intention, and greater affective commitment. In view of these results, it is suggested that there may be opportunities for organisations to improve individual and organisational effectiveness by engendering trust throughout peer levels.
A Game Engine in Pure Python for CS1: Design, Experience, and Limits

Games are being increasingly used to create compelling assignments for students learning programming, and Python is often used as an initial programming language. To that end, we present a game engine written in pure Python. Not only does the engine integrate seamlessly with what students already know about Python, but the game engine code itself is not a "black box" -- it is readable and approachable for beginning students. We report on two years' worth of experience using our game engine in CS1 for both regular assignments as well as "master classes," the engine's design, and its limits.
A “Neuropsychoanalytic” Treatment of a Patient with Cocaine Dependence

Although the use of neuroscience facts in psychoanalytic interpretations appears to be a widespread activity, it is not clear to some analysts how neuroscience is used in treatments. A specific case example of the common psychopathology of addiction is given with a retrospective review of verbatim notes from the first 60 hours of a 5-day-per-week treatment. It is acknowledged that it may be difficult to precisely categorize each interpretation, but the overall impact of neurobiology on the associations of the patient and the interpretations of the analyst is demonstrated. A counterexample from Kernberg (2007) is cited to show how knowing and using neuroscience leads to differing formulations and interpretations than when the analyst uses a purely idealist approach. The use of neuropsychoanalytic interpretations of motivations that must be unconscious by virtue of their origin in midbrain structures is contrasted with cognitive-behavioral treatment for cocaine dependence that uses a learning-teaching model. A neuropsychoanalytic treatment is not reductionistic by insisting that neurobiology is the only possible way of thinking about the exchanges between the patient and the analyst. However, by anchoring the model of psychopathology in material reality, it avoids an idealist drift away from science and allows the possibility that testable hypotheses will emerge from empathic observations. Use of neuroscience in psychoanalytic treatments takes advantage of the origin of Freud’s model to preserve its virtues and extend its range.
Speech Graphs Provide a Quantitative Measure of Thought Disorder in Psychosis

Background Psychosis has various causes, including mania and schizophrenia. Since the differential diagnosis of psychosis is exclusively based on subjective assessments of oral interviews with patients, an objective quantification of the speech disturbances that characterize mania and schizophrenia is in order. In principle, such quantification could be achieved by the analysis of speech graphs. A graph represents a network with nodes connected by edges; in speech graphs, nodes correspond to words and edges correspond to semantic and grammatical relationships. Methodology/Principal Findings To quantify speech differences related to psychosis, interviews with schizophrenics, manics and normal subjects were recorded and represented as graphs. Manics scored significantly higher than schizophrenics in ten graph measures. Psychopathological symptoms such as logorrhea, poor speech, and flight of thoughts were grasped by the analysis even when verbosity differences were discounted. Binary classifiers based on speech graph measures sorted schizophrenics from manics with up to 93.8% of sensitivity and 93.7% of specificity. In contrast, sorting based on the scores of two standard psychiatric scales (BPRS and PANSS) reached only 62.5% of sensitivity and specificity. Conclusions/Significance The results demonstrate that alterations of the thought process manifested in the speech of psychotic patients can be objectively measured using graph-theoretical tools, developed to capture specific features of the normal and dysfunctional flow of thought, such as divergence and recurrence. The quantitative analysis of speech graphs is not redundant with standard psychometric scales but rather complementary, as it yields a very accurate sorting of schizophrenics and manics. Overall, the results point to automated psychiatric diagnosis based not on what is said, but on how it is said.
The use of written transcripts in powerful and powerless language research

This study tested the salience of hesitations and hedges in a simulated student government situation. Subjects reported more hesitations in writing but noted more hedges on tape. Award amounts were significantly higher when powerless testimony was delivered orally rather than in writing. No similar effect was found for credibility ratings. Implications of these findings in light of the “hammer effect”; are discussed.
Japan ’ s First Operation of High-Temperature Superconducting Cable Systems in Live Grids ( High-Temperature Superconducting Cable Demonstration Project )

The reduction of CO2 emissions to combat global warming is one of the most pressing issues in the electric power business; however, the fact is that no measures are currently available that would effectively reduce electric power transmission and distribution losses, which currently hover around 5%. Likewise, the replacement of large-capacity pipe-type oil-filled cables (POF cables), which are becoming obsolete, is expected to go into full swing sometime around 2016. Replacing them with lowcapacity cross-linked polyethylene vinyl sheath cables (CV cables), however, requires additional circuits, which is rather impractical due to the difficulties inherent in constructing new cable tunnels in urban districts. Because they fit large-capacity, low-loss power transmission hardware into a compact package (1), high-temperature superconducting (HTS) cables are expected to offer innovative solutions to these technical bottlenecks. They have therefore been identified as a key technology for the development of next-generation power transmission grids, and a number of development and demonstration projects are currently underway around the world. Sumitomo Electric Industries, Ltd. has been pursuing the development of HTS wires from the time that HTS materials were first discovered in 1986, and by using HTS wires, it has been working to develop “3-in-One” HTS cables since 1991 (2), (3). Sumitomo Electric became the first in the world to succeed in electricity transmission on a live grid with these cables in the Albany Project in the United States in 2006 (4). Since that time, this long-term demonstration has progressed satisfactorily, unattended for a total of nearly nine months of electricity transmission (5). In the United States, several HTS cable demonstration projects have been conducted in actual power grids; however, no in-grid demonstration is conducted in Japan’s power grids. Because of this, in 2007, the New Energy and Industrial Technology Development Organization (NEDO) commenced the High-temperature Superconducting Cable Demonstration Project, the first operation of HTS cables in a live grid in Japan. Sumitomo Electric has been participating in this project to demonstrate the reliability of HTS cable systems in Japan’s power system. This paper describes the development status of HTS cables in this project and the results of verification conducted prior to the demonstration.
Optimal Diversification: Reconciling Theory and Evidence

In this paper we show that the main empirical findings about firm diversification and performance are consistent with the maximization of shareholder value. In our model, diversification allows a firm to explore better productive opportunities while taking advantage of synergies. By explicitly linking the diversification strategies of the firm to differences in size and productivity, our model provides a natural laboratory to investigate several aspects of the relationship between diversification and performance. Specifically, we show that our model can rationalize the evidence on the diversification discount ( Lang and Stulz (1994) ) and the documented relation between diversification and productivity ( Schoar (2002) ). Copyright 2004 by The American Finance Association.
Image Quality Metrics: PSNR vs. SSIM

In this paper, we analyse two well-known objective image quality metrics, the peak-signal-to-noise ratio (PSNR) as well as the structural similarity index measure (SSIM), and we derive a simple mathematical relationship between them which works for various kinds of image degradations such as Gaussian blur, additive Gaussian white noise, jpeg and jpeg2000 compression. A series of tests realized on images extracted from the Kodak database gives a better understanding of the similarity and difference between the SSIM and the PSNR.