cssi/SciSciGPT-SciSciNet huggingface dataset:
Dissecting the Mechanism of Endogenous GATA-2 Transcription: GATA Factor Interplay at Multiple Upstream Regulatory Regions Establishes Long-Range Transcriptional Control.

Given the simplicity of the DNA sequence that mediates binding of GATA transcription factors, GATA motifs reside throughout chromosomal DNA. However, analyses of GATA-1 occupancy by chromatin immunoprecipitation (ChIP) revealed that GATA-1 discriminates exquisitely among these sites. GATA-2 selectively occupies the −2.8 kb region of the GATA-2 locus in the active state, despite there being numerous GATA motifs throughout the locus. The GATA-1-mediated displacement of GATA-2 is tightly coupled to repression of GATA-2 transcription. We have used high-resolution ChIP to show that GATA-1 and GATA-2 occupy two additional regions, −3.9 kb and −1.8 kb of the GATA-2 locus. GATA-1 and GATA-2 had distinct preferences for occupancy at these regions, with GATA-1 and GATA-2 occupancy highest at the −3.9 kb and −1.8 kb regions, respectively. Activation of an estrogen receptor fusion to GATA-1 (ER-GATA-1) induced similar kinetics of ER-GATA-1 occupancy and loss of GATA-2 occupancy at the sites. As the distinct preferences for GATA factor occupancy were not evident from electrophoretic mobility shift assay analysis in vitro , establishment of the preferences requires the native nucleoprotein structure of the GATA-2 locus. In the transcriptionally active state, the −3.9 kb and −1.8 kb regions formed strong DNaseI hypersensitive sites (HSs), and the −2.8 kb region formed a weak HS. Whereas ER-GATA-1-instigated repression abolished the −1.8 kb HS, the −3.9 kb HS persisted in the inactive state. Transient transfection analysis provided evidence that the −3.9 kb region functions distinctly from the −2.8 kb and −1.8 kb regions. Molecular studies, including capturing chromosome conformation (3C) analysis, are underway to dissect the structure/function of the upstream regulatory regions. Based on the high sequence conservation and occupancy by GATA factors in vivo , targeted deletions of the −2.8 kb and −1.8 kb regions were generated. Mutant mice are being developed, and functional analysis is being conducted via in vitro differentiation of homozygous mutant ES cells. Our results support a model in which dynamic changes in GATA factor occupancy and chromatin structure at the −3.9 kb, −2.8 kb, and −1.8 kb regions are intimately controlled by Friend of GATA-1 and additional coregulators. This GATA factor interplay is essential for GATA-2 transcriptional regulation and therefore the control of hematopoiesis.
O-GlcNAcylation of α-Synuclein at Serine 87 Reduces Aggregation without Affecting Membrane Binding

The aggregation of neurodegenerative-disease associated proteins can be affected by many factors, including a variety of post-translational modifications. One such modification, O-GlcNAcylation, has been found on some of these aggregation prone proteins, including α-synuclein, the major protein that plays a causative role in synucleinopathies like Parkinson’s disease. We previously used synthetic protein chemistry to prepare α-synuclein bearing a homogeneous O-GlcNAc modification at threonine 72 and showed that this modification inhibits protein aggregation. However, the effects of the other eight O-GlcNAcylation sites that have been identified were unknown. Here, we use a similar synthetic strategy to investigate the consequences of this modification at one of these sites, serine 87. We show that O-GlcNAcylation at this site also inhibits α-synuclein aggregation but to a lesser extent than that for the same modification at threonine 72. However, we also find that this modification does not affect the mem...
E-Book Usage: Role of Environmental Consciousness, Personality and past Usage

E-books are a relatively new phenomenon and correspondingly, there is limited research on the factors associated with e-book usage especially in relation to printed books. In this research it is, therefore, of interest to examine antecedents of e-book usage intentions in one conceptual framework. The study was conducted using a course e-book. Findings reveal that environmental consciousness lowers the preference for printed books, and augments the design evaluation of the e-book. Personality factors impact the preference for printed books and perceived design evaluation of the e-book in different ways. A preference for printed books reduces, whereas perceived positive navigational design enhances, the attitude toward e-book usage. The findings have theoretical and practical implications. This study is one of the first to systematically study the e-book usage antecedents in a holistic manner, and also the first to examine the role of environmental consciousness in impacting e-book usage intentions in general.
Can probability theory explain why closure is both intuitive and prone to counterexamples

Epistemic closure under known implication is the principle that knowledge of $$\varphi$$ and knowledge of $$\varphi \rightarrow \psi$$ , together, imply knowledge of $$\psi$$ . This principle is intuitive, yet several putative counterexamples have been formulated against it. This paper addresses the question, why is epistemic closure both intuitive and prone to counterexamples? In particular, the paper examines whether probability theory can offer an answer to this question based on four strategies. The first probability-based strategy rests on the accumulation of risks. The problem with this strategy is that risk accumulation cannot accommodate certain counterexamples to epistemic closure. The second strategy is based on the idea of evidential support, that is, a piece of evidence supports a proposition whenever it increases the probability of the proposition. This strategy makes progress and can accommodate certain putative counterexamples to closure. However, this strategy also gives rise to a number of counterintuitive results. Finally, there are two broadly probabilistic strategies, one based on the idea of resilient probability and the other on the idea of assumptions that are taken for granted. These strategies are promising but are prone to some of the shortcomings of the second strategy. All in all, I conclude that each strategy fails. Probability theory, then, is unlikely to offer the account we need.
The role of the leukemia inhibitory factor receptor in neuroprotective signaling.

Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190 kDa subunit couples with the 130 kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison. This review examines the role of this receptor in the CNS and immune system, and its application in the treatment in stroke and other brain pathologies.
Meta‐Analysis of Time in Therapeutic Range in Continuous‐Flow Left Ventricular Assist Device Patients Receiving Warfarin

Continuous-flow left ventricular assist devices (CF-LVADs) prolong survival in advanced heart failure patients. Anticoagulation control is critical in CF-LVAD patients due to increased thromboembolic and bleeding risk. We assessed the quality of INR control in CF-LVAD patients measured by time in therapeutic range (TTR). We performed a systematic literature search of MEDLINE and SCOPUS through July 2017 to identify studies evaluating TTR in anticoagulated adult CF-LVAD patients. Data on key characteristics and the TTR end point were then extracted from each study by two investigators using a standardized tool. Using a Hartung-Knapp random effects model, a weighted mean TTR estimate with accompanying 95% confidence interval (CI) was calculated. Statistical heterogeneity was estimated using the I2 statistic. Five published studies were included. All studies were single-center, retrospective investigations that calculated TTR using the Rosendaal method. Sample sizes ranged from 11 to 115 patients (total of 270 patients) with durations of follow-up ranging from 9 to 76 person-years. On meta-analysis, CF-LVAD patients had a weighted mean TTR of 46.6% (95% CI: 36.0-57.3%, I2 = 94%). This suggests that warfarin is difficult to manage in CF-LVAD patients, which may contribute to high rates of bleeding and thromboembolic complications.
How changes in the house advantages of reel slots affect game performance.

In two-game pairings of otherwise identical reel slot machines, the games with greater pars outperformed those with lesser pars. This finding held across five pairings, three casinos, three gaming ...
Contemporary Challenges to Theism: Evil and Suffering

There has been perhaps no greater challenge to theism than the perceived existence of evil and suffering in the world. The challenge is an ancient one and has persevered through many centuries of analysis and response because the problem of reconciling the existence of evil in this world with the existence of an all-powerful, all-knowing, and all-loving God seems to be so utterly basic and intractable. In Judaism and Christianity, the problem can be traced back at least as far as the book of Job, where the ancient writer tries to address the profound human bewilderment at the sometimes overwhelming effect of the existence of evil and suffering in this world when God has seemingly “hidden his face” from human beings. The response provided by the book of Job is one that takes refuge in the total mysteriousness and transcendency of God and God’s nature. In the dialogue between Job and God when God finally responds to Job’s questioning, we find one of the classic representations of mysticism, which emphasizes the finite limitations and worthlessness of human beings and their inability to understand God, God’s nature, or God’s ways. The biblical passages from this exchange between Job and God have become cornerstones of a certain kind of response even by contemporary theists. In apparently angry and defiant words, God overwhelms Job as a whirlwind: “Where were you when I laid the foundation of the earth? Tell me if you have understanding. Who determined its measurements — surely you know. Or who stretched the line upon it? On what were its bases sunk, or who laid its cornerstone, when the morning stars sang together, and all the sons of God shouted for joy?” (Job 38:4–7). God concludes the response to Job by asking (rhetorically and angrily), “Shall a faultfinder contend with the Almighty? He who argues with God, let him answer it” (Job 40:1–2). Leaving the problem of the existence of evil and human and animal suffering simply as an unresolved matter that human reason cannot fathom because of the incomprehensible nature of the deity does not address the problem adequately. The inadequacy of such a response is evidenced by the fact that, in the history of the philosophy of religion, more attention has been devoted to what is now called “the problem of evil” than to any ther single aspect of modern theism, and the same certainly continued throughout the twentieth century.
Analogical replay for efficient conditional planning

Recently, several planners have been designed that can create conditionally branching plans to solve problems which involve uncertainty. These planners represent an important step in broadening the applicability of AI planning techniques, but they typically must search a larger space than non-branching planners, since they must produce valid plans for each branch considered. In the worst case this can produce an exponential increase in the complexity of planning. If conditional planners are to become usable in real-world domains, this complexity must be controlled by sharing planning effort among branches. Analogical plan reuse should playa fundamental role in this process. We have implemented a conditional probabilistic planner that uses analogical plan replay to derive the maximum benefit from previously solved branches of the plan. This approach provides valuable guidance for when and how to merge different branches of the plan and exploits the high similarity between the different branches in a conditional plan, which have the same goal and typically a very similar state. We present experimental data in which analogical plan replay significantly reduces the complexity of conditional planning. Analogical replay can be applied to a variety of conditional planners, complementing the plan sharing that they may perform naturally.
The Prophets as Social Reformers

In the earliest Israelite literature, Yahweh is a national god concerned primarily with the military security and material prosperity of his people. Threats of punishment and doom directed at this people arise only for the worship of foreign gods whose exemplars are the Baalim. All this changes in the eighth-seventh centuries B.C.E. with the classical prophets.
Removing a barrier to computer-based outbreak and disease surveillance--the RODS Open Source Project.

Introduction: Computer-based outbreak and disease surveillance requires high-quality software that is well-supported and affordable. Developing software in an open-source framework, which entails free distribution and use of software and con tinuous, community-based software development, can produce software with such characteristics, and can do so rapidly. Objectives: The objective of the Real-Time Outbreak and Disease Surveillance (RODS) Open Source Project is to accelerate the deployment ofcomputer-based outbreak and disease surveillance systems by writing software and catalyzing the formation of a community of users, developers, consultants, and scientists who support its use. Methods: The University of Pittsburgh seeded the Open Source Project by releasing the RODS software under the GNU General Public License. An infrastructure was created, consisting of a website, mailing lists for developers and users, desig nated software developers, and shared code-development tools. These resources are intended to encourage growth of the Open Source Project community. Progress is measured by assessing website usage, number of software downloads, number of inquiries, number of system deployments, and number of new features or modules added to the code base. Results: During September-November 2003, users generated 5,370page views of the project website, 59 software downloads, 20 inquiries, one new deployment, and addition of four features. Conclusions: Thus far, health departments and companies have been more interested in using the software as is than in custom izing or developing new features. The RODS laboratory anticipates that after initial installation has been completed, health departments and companies will begin to customize the software and contribute their enhancemeyits to the public code base.
Schrödinger Theory from a “Newtonian” Perspective

Time-independent quantal density functional theory (Q-DFT) [1] is a description of the mapping from a system of electrons in an external field in their ground or excited state as described by Schrodinger theory, to a model system of noninteracting fermions – the S system – whereby the equivalent density ρ(r), the energy E, and the ionization potential I are obtained. The reason for the mapping to the model S system is that for a system of N electrons, it is easier to solve the corresponding N model-fermion single-particle differential equations than it is to solve the single N-electron Schrodinger equation. The model system is described by Q-DFT via a “Newtonian” perspective. This perspective is in terms of fields that are “classical” in nature and which pervade all space, but whose sources are quantal in that they are quantum-mechanical expectations of Hermitian operators or of the complex sum of Hermitian operators. As the model system is in effect a representation of the interacting system, it is best to first describe Schrodinger theory [2] from the same “Newtonian” perspective of “classical” fields and quantal sources [3, 4]. This perspective of Schrodinger theory is new. To quote from Einstein and Infeld [5]: “A new concept appeared in physics, the most important invention since Newton’s time: the field. It needed great scientific imagination to realize that it is not the charges nor the particles but the field in the space between the charges and particles that is essential for the description of the physical phenomenon.” These remarks were made with reference to the classical physics of Faraday and Maxwell. Einstein and Infeld may not have imagined then that nonrelativistic QuantumMechanics/Schrodinger theory too could be similarly described in terms of fields that are “classical” in nature but which arise from sources that are quantal.
Effects of nicotine and stress exposure across generations in C57BL/6 mice

Chronic administration of nicotine or exposure to stress can produce long-lasting behavioral and physiological changes in humans and animals alike. Further, the impact of nicotine and stress exposure can be inherited by offspring to produce persistent changes in physiology and behavior. To determine if nicotine and stress interact across generations to influence offspring behavior we exposed F0 male mice to nicotine and F1 male and female mice to chronic unpredictable stress during adolescence. We then measured locomotor sensitization to repeated nicotine injections in the subsequent F2 and F3 generations. Stress exposure alone (F1) did not influence locomotor sensitization in any lineage. However, in the F1 male lineage, F0 nicotine exposure abrogated locomotor sensitization in F2 male and transiently enhanced locomotor sensitization in F2 female offspring. These effects were not passed down to the F3 generations or observed in the F1 female lineage. F1 stress exposure modulated the effects of prior F0 nicotine exposure in a sex-dependent manner. Specifically, stress blunted the nicotine-induced enhancement in locomotor sensitization observed in F2 female offspring of F1 males. The effect of F0 nicotine and F1 stress exposure in females appears to have skipped a generation and enhanced nicotine sensitization only in the F3 generation, and only in females. This novel multigenerational exposure paradigm examining the inheritance of two different environmental exposures demonstrates that nicotine responses can be modified by nicotine and stress exposure from previous generations, and these effects are strongly influenced by sex.
IVAS: Facilitating Safe and Comfortable Driving with Intelligent Vehicle Audio Systems

Vehicle audio systems affect safety and comfortability of daily driving, as a driver’s mental or physical state can be significantly influenced by his or her audio perception during the maneuver. In this paper, we propose an intelligent vehicle audio systems (IVAS) by leveraging recent advances in automated driving, recommender system, and audio synthesis in an end-to-end fashion. Our contributions are multifold: (i) we design a deep deterministic policy gradients (DDPG) for adaptive control of an automated vehicle equipped with multi-sensors; (ii) we incorporate an unidirectional long short-term memory (LSTM) units of a recurrent neural network (RNN) with a recurrent output layer for audio synthesis; and (iii) we integrate above techniques into an end-to-end framework and pioneer the next generation vehicle audio system—IVAS. A psychological study is also performed to demonstrate the effectiveness of the proposed framework.
AHFME Member 1995 Total Annual Earnings Survey

ABSTRACT This study was conducted to determine the 1995 annual earnings of hospitality financial management educators. Nearly fifty percent of AHFME's members responded. Annual base salaries ranged from $28,000 to $105,000. The lowest-paid member is an instructor while the highest-paid member is a full professor. Most respondents supplement their base salaries by teaching during summer school and conducting consulting. The total annual earnings of members ranged from $30,000 to $158,250. Hospitality financial management educators appear to be more highly compensated than hospitality industry financial executives.
Cancer survivors’ challenges with ostomy appliances and self-management.

e23091Background: Ostomies adversely affect health-related quality of life among cancer survivors. Survivors and their families must engage in ostomy self-management, make substantial behavior chan...
Comparison of Self-controlled Designs for Evaluating Outcomes of Drug-Drug Interactions: Simulation Study.

BACKGROUND Self-controlled designs, both case-crossover and self-controlled case series, are well suited for evaluating outcomes of drug-drug interactions in electronic healthcare data. Their comparative performance in this context, however, is unknown. METHODS We simulated cohorts of patients exposed to two drugs: a chronic drug (object) and a short-term drug (precipitant) with an associated interaction of 2.0 on the odds ratio scale. We analyzed cohorts using case-crossover and self-controlled case series designs evaluating exposure to the precipitant drug within person-time exposed to the object drug. Scenarios evaluated violations of key design assumptions: (1) time-varying, within-person confounding; (2) time trend in precipitant drug exposure prevalence; (3) nontransient precipitant exposure; and (4) event-dependent object drug discontinuation. RESULTS Case-crossover analysis produced biased estimates when 30% of patients persisted on the precipitant drug (estimated OR 2.85) and when the use of the precipitant drug was increasing in simulated cohorts (estimated OR 2.56). Self-controlled case series produced biased estimates when patients discontinued the object drug following the occurrence of an outcome (estimated incidence ratio [IR] of 2.09 [50% of patients stopping therapy] and 2.22 [90%]). Both designs yielded similarly biased estimates in the presence of time-varying, within-person confounding. CONCLUSION In settings with independent or rare outcomes and no substantial event-dependent censoring (<50%), self-controlled case series may be preferable to case-crossover design for evaluating outcomes of drug-drug interactions. With frequent event-dependent drug discontinuation, a case-crossover design may be preferable provided there are no time-related trends in drug exposure.
Characterization of new chloroplast markers to determine biogeographical origin and crop type of Cannabis sativa

Marijuana (Cannabis sativa) is the most commonly used illicit drug in the USA. Despite its schedule I classification by the federal government, 33 states and the District of Columbia have legalized its use for medicinal or recreational purposes. This state-specific legalization has created a new problem for law enforcement: preventing and tracking the diversion of legally obtained Cannabis to states where it remains illegal. In addition, trafficking of the drug at the border with Mexico remains an issue for law enforcement agencies. C. sativa crops can be classified as marijuana (a drug containing the psychoactive chemical delta-9-tetrahydrocannabinol) or hemp (the non-drug form of the plant). Differentiation between crop types is important for forensic purposes. In addition, investigation of trafficking routes into and within the USA requires genetic association of samples from different seizures, and determining where the crop originated could provide important leads. This project seeks to exploit sequence variations in C. sativa chloroplast DNA (cpDNA) to allow genetic determination of biogeographic origin, discrimination between marijuana and hemp, and association between cases for C. sativa samples. Due to the limited discriminatory ability of common barcoding markers, the authors sought to discover more informative polymorphic regions. By comparing published whole genome cpDNA sequences, 58 polymorphisms and seven hotspot regions were identified. Hemp samples from the USA and Canada, marijuana samples from Mexico and Chile, and medical marijuana samples from Chile were evaluated using two cpDNA hotspot regions, rpl32-trnL and trnS-trnG. Principal component analysis supported some differences between the groups based on their crop type and biogeographic origin.
Spin-Orbit Torque Driven One-Bit Magnetic Racetrack Devices - Memory and Neuromorphic Applications

Recent breakthroughs on spin-orbit torque have opened door to more versatile magnetic racetrack memory. Especially, spin-orbit torque driven one-bit three terminal racetrack memory is promising to develop field-free memory and neuromorphic devices that have many figure of merits. However, there are quite a few challenges to overcome to have working racetrack devices such as decent tunneling magnetoresistance, low threshold current density, and homogeneous films. We present here successfully fabricated one-bit three terminal magnetic racetrack devices in which the position of domain wall is readout by magnetic tunnel junctions.
Unbridled Stallions and Mad Bulls: Masculinity, Race, and Sexuality in Hemispheric Perspective

This article juxtaposes two very different authors from very different locations: George Winston, a largely forgotten Southern college president during the Jim Crow era in the United States, and Gi...
Improved Synthetic Training for Reading Comprehension.

Automatically generated synthetic training examples have been shown to improve performance in machine reading comprehension (MRC). Compared to human annotated gold standard data, synthetic training data has unique properties, such as high availability at the possible expense of quality. In view of such differences, in this paper, we explore novel applications of synthetic examples to MRC. Our proposed pre-training and knowledge distillation strategies show significant improvements over existing methods. In a particularly surprising discovery, we observe that synthetic distillation often yields students that can outperform the teacher model.
Alcohol, Amino Acids, and Encephalopathy

Encephalopathy is a severe and common complication of cirrhosis, including alcoholic cirrhosis, but its pathogenesis is not fully understood. Several new theories have been proposed, and many have emphasized the importance of plasma amino acids. Recent studies have called into question the hypothesis that the ratio of aromatic to branched-chain amino acids in plasma is the key abonormality in this disorder.
The Hepatorenal Syndrome (HRS)

Progressive oliguric renal failure commonly complicates the course of patients with advanced hepatic disease (1,2). While this condition has been designated by many names including “functional renal failure”, and “the renal failure of cirrhosis”, the more appealing albeit less specific term “hepatorenal syndrome” has been utilized commonly to describe this syndrome. For the purposes of this discussion, the hepatorenal syndrome may be defined as unexplained progressive renal failure occurring in patients with liver disease in the absence of clinical, laboratory, or anatomic evidence of other known causes of renal failure.
Intra-renal localization of b2-microglobulin (b2-m) in renal transplant material. An immunohistochemical study.

Summary The distribution of b 2 -m immunoreactivity in biopsy material (paraffin sections) of 34 patients with renal transplantation was examined. b 2 -m was present along the glomerular capillary walls and in cytoplasm of the epithelial cells of convoluted tubules and mainly towards their basement membranes in 15 out of 17 with acute rejection, in 5 out of 8 with chronic rejection and only one case of normal donor. The more frequent detection and the more intense staining of b 2 -m in acute kidney rejection are discussed.
Angiographic characteristics of definite stent thrombosis: role of thrombus grade, collaterals, epicardial coronary flow, and myocardial perfusion.

Objectives To characterize the prevalence of thrombus burden, collateral vessels to the infarct-related artery, epicardial coronary artery flow, and myocardial perfusion in patients with angiographically confirmed definite stent thrombosis (ST), and to define their relationship with associated treatments and outcomes. Background Angiographic characteristics of ST are not well defined. Methods All cases of angiographically determined ST at five academic hospitals from 2005 to 2012 were reviewed. Demographic, procedural, and angiographic characteristics were recorded. In-hospital and 1-year follow-up data were obtained. Results Among 205 cases of angiographic definite ST (60 ± 8 years; 87% male), the majority presented with late/very late ST (69%) and STEMI (66%). High-risk angiographic findings at presentation included thrombus grade 4–5 (87%), absence of collateral vessels (76%), and reduced initial TIMI 3 flow (90%). Final TIMI 3 flow was achieved in 90% of patients and was associated with greater use of aspiration thrombectomy (60% vs. 25%; P = 0.003), glycoprotein IIb/IIIa inhibitors (80% vs. 30%, P < 0.001), and repeat stenting (67% vs. 10%, P < 0.001). A final myocardial perfusion grade of 2–3 was achieved in 79% of patients and was associated with greater use of aspiration thrombectomy (61% vs. 36%, P = 0.003). After multivariable logistic regression, aspiration thrombectomy (AOR 2.6, 95% CI 1.3–5.2) and implantation of a new stent (AOR 2.1, 95% CI 1.1–4.3) were associated with optimal combined epicardial flow and myocardial perfusion. At 1-year follow-up, significantly lower risk of repeat ST (HR 0.1; 95% CI 0.1,0.2; P < 0.001) among patients with initial TIMI 3 flow at index ST was observed. Conclusions The majority of ST patients present with late/very late ST with high thrombus burden and STEMI. Presence of collateral vessels and low thrombus burden is cardioprotective, while reduced initial TIMI flow is associated with larger infarct size and recurrent ST. Aspiration thrombectomy and repeat stenting are associated with improved epicardial coronary artery flow and myocardial perfusion among patients treated for ST. © 2014 Wiley Periodicals, Inc.
Safety and efficacy of bivalirudin for percutaneous coronary intervention with rotational atherectomy.

Background: Although bivalirudin use in percutaneous coronary intervention (PCI) results in less bleeding compared to unfractionated heparin (UFH) use, its safety in patients undergoing rotational atherectomy (RA) is unknown. Methods: A cohort of 503 patients who underwent PCI with RA from 2000 to 2009 was studied. Patients receiving bivalirudin (n = 322) were compared to those (n = 181) treated with UFH ± glycoprotein IIb/IIIa inhibitor (GPI) as PCI anticoagulation. Safety was assessed by the frequency of major bleeding (hematocrit drop ≥15%, intracerebral or gastro-intestinal bleeding) and need for transfusion. Efficacy was assessed by a composite end-point of in-hospital death, Q wave myocardial infarction (MI) or urgent coronary artery bypass graft (CABG). Results: Those in the bivalirudin group were older, more hypertensive, and had greater body mass index. The UFH group was more likely to have prior MI, prior CABG, and an acute coronary syndrome at baseline. GPI was used in 93 patients (52%) of the UFH group. No difference was found between groups for the composite of death/Q wave MI/urgent CABG (1.9% vs. 1.7%, respectively, in bivalirudin vs. UFH group; P = 0.2). The frequency of major bleeding (2.2% vs. 1.7%; P = 0.8) or transfusion (5.6% vs. 8.7%; P = 0.9) was also similar between groups. After adjustment, bivalirudin use was not associated with a reduction in death/Q wave MI/urgent CABG, major bleeding, or transfusion compared to UFH. Conclusion: Bivalirudin use seems to be as safe and effective as UFH in patients undergoing RA. (J Interven Cardiol 2010;23:223–229)
The paraoxonase‐1 pathway is not a major bioactivation pathway of clopidogrel in vitro

BACKGROUND AND PURPOSE Clopidogrel is a prodrug bioactivated by cytochrome P450s (CYPs). More recently, paraoxonase-1 (PON1) has been proposed as a major contributor to clopidogrel metabolism. The purpose of this study was to assess the relative contribution of CYPs and PON1 to clopidogrel metabolism in vitro. EXPERIMENTAL APPROACH Clopidogrel metabolism was studied in human serum, recombinant PON1 enzyme (rePON1), pooled human liver microsomes (HLMs), HLMs with the CYP2C19*1/*1 genotype and HLMs with the CYP2C19*2/*2 genotype. Inhibition studies were also performed using specific CYP inhibitors and antibodies. Clopidogrel and its metabolites were measured using LC/MS/MS method. KEY RESULTS PON1 activity was highest in the human serum and there was no difference in PON1 activity between any of the HLM groups. The production of clopidogrel's active metabolite (clopidogrel-AM) from 2-oxo-clopidogrel in pooled HLMs was approximately 500 times that in serum. When 2-oxo-clopidogrel was incubated with rePON1, clopidogrel-AM was not detected. Clopidogrel-AM production from 2-oxo-clopidogrel was lower in CYP2C19*2/*2 HLMs compared with CYP2C19*1/*1 HLMs, while PON1 activity in HLMs with both genotypes was similar. Moreover, incubation with inhibitors of CYP3A, CYP2B6 and CYP2C19 significantly reduced clopidogrel bioactivation while a PON1 inhibitor, EDTA, had only a weak inhibitory effect. CONCLUSION AND IMPLICATIONS This in vitro study shows that the contribution of PON1 to clopidogrel metabolism is limited at clinically relevant concentrations. Moreover, CYP2C19, CYP2B6 and CYP3A play important roles in the bioactivation of clopidogrel.
A Comparison of Genetic Algorithm Methods In Aerial Spray Deposition Management

In this paper, we describe several genetic algorithm methods to deal with the spray parameter optimization problem, and compare them with the original heuristic method SAGA.
Natural Environments or Naturalistic Learning Opportunities: What Is the Evidence in Early Intervention?

The term natural environments first appeared in 1989 in the regulations for the “Education of the Handicapped Act” amendments of 1986 and reappeared in the 1991 and 2004 amendments to the public la...
Thermoelectric Energy Harvesting Snow Pants: Turning Body Heat Into Usable Energy

Using thermoelectric coolers (TECs), energy generated from a temperature gradient can solve the problem of energy inaccessibility and provide energy readily. The purpose of this study was to create snow pants that could harness and convert body heat into energy. It was hypothesized that if there was more surface area in the insulation layers of the snow pants, then more heat will be collected. It was determined that the most effective and efficient way to harvest energy from body heat was by using TECs that were sewn into a pair of snow pants. Snow pants were chosen because the interior and exterior have drastically different temperatures that create a temperature gradient, which could ultimately increase the voltage output. Three prototypes were built and all produced enough voltage, which can be and will eventually be amplified. Once the voltage is amplified, an electronic device will have direct access to power within the pants’ pocket via a USB port. Thermoelectric energy presents an innovative and viable option as an energy solution. Using TECs, heat-harvesting backpacks, coolers, sleeping bags and more can be produced, making the world a more connected and greener place. Des refroidisseurs thermoelectriques (RTE) qui englobent « l’effet de Peltier » peuvent produire de l’energie provenant d’un gradient de temperature et se posent comme solution au probleme de l’inaccessibilite a l’energie en fournissant de l’energie partout et a tout moment. Le but de cette etude etait de creer des pantalons de neige qui pourraient exploiter et convertir la chaleur corporelle a l’energie. L’hypothese etant que l’existence de plus de superficie dans les couches d’isolation des pantalons de neige aurait pour effet plus de chaleur rassemblee. Il a ete determine que la facon la plus efficace de collecter de l’energie de par la chaleur corporelle etait en incorporant les RTEs par couture dans une paire de pantalons de neige. Les pantalons de neige ont ete le vetement de choix car la temperature mesure a leur interieur et a leur exterieur est dramatiquement differente ce qui genere ainsi un gradient de temperature qui pourrait ultimement augmenter la tension produite. Trois prototypes ont ete fabrique et tous ont produit de la tension, assez qui peut etre et sera finalement amplifie. Une fois que la tension est amplifiee, un dispositif electronique aura acces direct au fonctionnement de l’interieure de la poche de pantalons via un port USB. L’energie thermoelectrique se positionne comme une solution d’energie tres novatrice et viable. En utilisant les RTE, la chaleur peut etre recolte des sacs a dos, des refroidisseurs d’aliments, les sacs de couchage, tous possible a etre produit faisant de ce monde un lieu plus interconnecte et plus sain pour l’environnement.
Multilevel methodology for simulation of spatio-temporal systems with heterogeneous activity: application to spread of valley fever fungus

Spatio-temporal systems with heterogeneity in their structure and behavior have two major problems. The first one is that such systems extend over very large spatial and temporal domains and consume a lot of resources to simulate that they are infeasible to study with current platforms. The second one is that the data available for understanding such systems is limited. This also makes it difficult to get the data for validation of their constituent processes while simultaneously considering their global behavior. For example, the valley fever fungus considered in this dissertation is spread over a large spatial grid in the arid Southwest and typically needs to be simulated over several decades of time to obtain useful information. It is also hard to get the temperature and moisture data at every grid point of the spatial domain over the region of study. In order to address the first problem, we develop a method based on the discrete event system specification which exploits the heterogeneity in the activity of the spatio-temporal system and which has been shown to be effective in solving relatively simple partial differential equation systems. The benefit of addressing the first problem is that it now makes it feasible to address the second problem. We address the second problem by making use of a multilevel methodology based on modeling and simulation and systems theory. This methodology helps us in the construction of models with different resolutions (base and lumped models). This allows us to refine an initially constructed lumped model with detailed physics-based process models and assess whether they improve on the original lumped models. For that assessment, we use the concept of experimental frame to delimit where the improvement is needed. This allows us to work with the available data, improve the component models in their own experimental frame and then move them to the overall frame. In this dissertation, we develop a multilevel methodology and apply it to a valley fever model. Moreover, we study the model's behavior in a particular experimental frame of interest, namely the formation of new sporing sites.
ANGIOGRAPHY OF THE CAPRINE DIGIT

Digital angiography of the caprine hindlimb was done via catheterization of dorsal metatarsal artery III. Good arteriograms were consistently produced. The vascular anatomy to the digit was similar to that reported in previous bovine studies. The caprine may be of use as a model for selected ruminant foot disease.
Transitioning to the Embedded Librarian Model and Improving the Senior Capstone Business Strategy Course

Abstract In collaboration with a strategy professor, a research librarian at a four-year SACS and AACSB-accredited Southern college transitioned from the one-time library instruction model to the role of an embedded librarian within a senior-level capstone course over a multi-year transition period. Through the use of multiple quantitative and qualitative assessment instruments, as well as anecdotal comments, and finally pre- and post-test student satisfaction and learning surveys, the library instruction and course requirements were revised. This course's implementation formed the basis of a campus-wide effort to embed librarians within on-campus and online/hybrid courses. Conclusions, discussion and areas for future research are included.
Multiple chirality transfers in the enantioselective synthesis of 11-O-debenzoyltashironin. Chiroptical analysis of the key cascade.

Abstract The mechanism of the cascade oxidative dearomatization–transannular Diels–Alder was investigated in the context of an asymmetric route to (−)-11-O-debenzoyltashironin. Although the oxidative dearomatization provides two acetal intermediates, the transannular Diels–Alder proceeds spontaneously from only one of the acetal isomers. Access to enantioenriched tetracyclic adduct was gained through the use of optically active allene.
The roles of stimulus repetition and hemispheric activation in visual half-field asymmetries

Abstract Hardyck, Tzeng, and Wang (1978, Brain and Language, 5, 56–71) hypothesized that ample repetition of a small number of stimuli is required in order to obtain VHF differences in tachistoscopic tasks. Four experiments, with varied levels of repetition, were conducted to test this hypothesis. Three experiments utilized the general task of object-picture naming and one utilized a word-naming task. Naming latencies constituted the dependent measure. The results demonstrate that for the object-naming paradigm repetition is required for RVF superiority to emerge. Repetition was found to be unnecessary for RVF superiority in the word-naming paradigm, with repetition actually reducing RVF superiority. Experiment I suggested the possibility that RVF superiority developed for the second half of the trials as a function of practice or hemispheric activation, regardless of repetition level. Subsequent experiments, better designed to assess this possibility, clearly refuted it. It was concluded that the effect of repetition depends on the processing requirements of the task. We propose that, for tasks which can be processed efficiently by one hemisphere, the effect of repetition will be to reduce VHF asymmetries; but tasks requiring substantial processing by both hemispheres will show shifts to RVF superiority as a function of repetition.
Carbonate in Hydroxylapatite.

Unit cell dimensions of hydroxylapatite synthesized hydrothermally are a 0 = 9.42 6 A and c 0 = 6.88 5 A, whereas carbonate apatite (2.29 CO 2 ) gave a 0 = 9.43 6 A and c 0 = 6.88 5 A. A deficiency of both calcium and phosphorus in the carbonate apatite suggests a coupled substitution of hydronium and carbonate ions in the structure.
Gauge dependence of the effective action

The gauge dependence of the effective action of quantum non-Abelian gauge theories is studied. An alternative effective action is proposed and its equivalence with the usual effective action is discussed, as well as the equivalence with't Hooft's effective action.
Roles of methionine suldfoxide reductases in antioxidant defense, protein regulation and survival

One of the most oxidation-sensitive amino acids is methionine. Oxidation of methionine to methionine sulfoxide (MetO) could, on the one hand, be an important component of signal transduction pathways and on the other hand, may lower the cellular antioxidant capacity, alter protein function, interfere with signal transduction, and damage proteins. The latter changes could lead to the accumulation and malfunction of various proteins. As a result, enhanced development of certain diseases and signs of aging may occur. So far, two major enzymes that could reduce MetO in proteins have been described, denoted as MsrA and MsrB (Methionine sulfoxide reductases). In general, Msrs have been shown to be important in protecting cells from oxidative stress throughout many species from bacteria to mammals. In addition, the activities of certain enzymes could be restored or controlled following reduction of their MetO residues, through the Msr system. Of all Msrs, MsrA seems to be important in controlling MetO reduction in general and MsrB, thioredoxin reductase (Trr), and the adhesion capabilities of certain bacterial cells in particular. The recently discovered MsrB can reduce specifically the R-MetO enantiomer while MsrA can reduce specifically the S-MetO enantiomer. Another significant difference between MsrA and MsrB is that the latter's major form in mammalian cells is a selenoprotein. The current review will discuss the major characteristics of methionine sulfoxide reductases as physiological antioxidants, repair systems, and cellular regulating enzymes.
A new model for granular porous media: Part II. Numerical solution of steady state incompressible Newtonian flow through periodically constricted tubes

A numerical method for the solution of the problem of steady state, incompressible Newtonian flow through periodically constricted tubes is developed. All terms of the Navier-Stokes equation are retained, including the nonlinear inertia terms. Sample calculations for a uniform periodically constricted tube, the geometry of which is connected with the modeling of a packed bed of sand are given, including streamlines, axial and radial velocity profiles, pressure profiles, and the dimensionless pressure drop versus Reynolds number relation. The effect of some geometric characteristics of periodically constricted tubes on their friction factor is investigated numerically, and comparison of some existing experimental data with calculated ones is made.
Infrared Sky Surveys

A retrospective is given on infrared sky surveys from Thomas Edison’s proposal in the late 1870s to IRAS, the first sensitive mid- to far-infrared all-sky survey, and the mid-1990s experiments that filled in the IRAS deficiencies. The emerging technology for space-based surveys is highlighted, as is the prominent role the US Defense Department, particularly the Air Force, played in developing and applying detector and cryogenic sensor advances to early mid-infrared probe-rocket and satellite-based surveys. This technology was transitioned to the infrared astronomical community in relatively short order and was essential to the success of IRAS, COBE and ISO. Mention is made of several of the little known early observational programs that were superseded by more successful efforts.
A 4-oxo-2(E)-nonenal-derived glutathione adduct from 15-lipoxygenase-1-mediated oxidation of cytosolic and esterified arachidonic acid.

Abstract 15(S)-Hydroperoxy-[5Z,8Z,11Z,13E]-eicosatetraenoic acid (15(S)-HpETE) undergoes homolytic decomposition to bifunctional electrophiles such as 4-oxo-2(E)-nonenal. 4-Oxo-2(E)-nonenal reacts with glutathione to form a thiadiazabicyclo-4-oxo-2(E)-nonenal–glutathione adduct (TOG). Therefore, this endogenous glutathione adduct can serve as a specific biomarker of lipid hydroperoxide-mediated 4-oxo-2(E)-nonenal formation. A monocyte/macrophage cell line was generated to constitutively express human 15-lipoxygenase-1. In these cells, TOG was formed from 15(S)-HpETE-derived 4-oxo-2(E)-nonenal in a nonlinear dose-dependent manner upon arachidonic acid treatment. The lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate abolished arachidonic acid-mediated TOG formation. The calcium ionophore A23187 was also used to induce the formation of 15(S)-HpETE from esterified arachidonic acid present in the membrane lipids. In the 15-lipoxygenase-1-expressing cells, the calcium ionophore A23187 significantly increased TOG levels compared with mock-transfected cells. This was due to the 15-lipoxygenase-mediated formation of 15(S)-HpETE in the forms of free fatty acid and esterified lipids, which was subsequently converted to 4-oxo-2(E)-nonenal. The increase in TOG formation was again abrogated by pretreatment with cinnamyl-3,4-dihydroxy-α-cyanocinnamate. Only 8.7% 15(S)-HETE (both the free fatty acid and its esterified form in the cell membrane) was formed after ionophore A23187 stimulation compared with that formed after the addition of arachidonic acid. In contrast, the TOG levels after treatment with ionophore A23187 or arachidonic acid were comparable. Thus, it is likely that esterified 15(S)-HpETE underwent homolytic decomposition to 4-oxo-2(E)-nonenal more efficiently than the free 15(S)-HpETE that was formed in the cytosol.