cssi/SciSciGPT-SciSciNet huggingface dataset:
QX-314 inhibits acid-induced activation of esophageal nociceptive C fiber neurons.

Introduction Acid reflux in the esophagus can induce painful sensations such as heartburn and non-cardiac chest pain. These nociceptive symptoms are initiated by activation of TRPV1-positive afferent C fibers in the esophagus. The present study aimed to explore a novel C fiber inhibition approach. We hypothesized that activation of TRPV1 by acid enabled QX-314, a membrane impermeable sodium channel blocker, to inhibit acid-induced activation of esophageal nociceptive C fiber neurons. Method We determined the inhibitory effect of QX-314 in the presence of acid in guinea pig esophageal nociceptive vagal jugular C fiber neurons by both patch clamp recording in neuron soma and by extra-cellular recording at nerve terminals. Key results Our data demonstrated QX-314 alone did not inhibit sodium currents. However, when applied along with capsaicin to activate TRPV1, QX-314 was able to block sodium currents in esophageal-specific jugular C fiber neurons. We then showed that in the presence of acid, QX-314 significantly blocked acid-evoked activation of jugular C fiber neurons. This effect was attenuated by TRPV1 antagonist AMG9810, suggesting acid-mediated inhibitory effect of QX-314 was TRPV1-dependent. Finally, we provided evidence at nerve endings that acid-evoked action potential discharges in esophageal jugular C fibers were inhibited by QX-314 when applied in the presence of acid. Conclusion and inferences Our data demonstrated that activation of TRPV1 by acid enabled membrane impermeable sodium channel blocker QX-314 to inhibit acid-induced activation in esophageal nociceptive C fibers. This supports a localized application of QX-314 in the esophagus to block esophageal nociception in acid reflux disorders.
Information Technology Doctoral Students: Challenges During the Dissertation Journey

The problem that is addressed in this paper is that information technologies (IT) doctoral students are not receiving the proper guidance and feedback they need to complete their dissertations. The purpose of this qualitative observational case study was to investigate the types of challenges IT doctoral students encounter as they complete their dissertation. A qualitative observational research design was used to collect data for the study. The data was collected between the years 2014 to 2018. Ten participants were used for the study, which were five professors and five IT doctoral students. The researchers of the current study observed how professors supervised students in IT doctoral projects. The researchers observed students from three universities in the southern part of the United States. Purposeful sampling was used to recruit participants. Thematic data analysis was used to analyze the data. The findings suggest that the doctoral team is not well trained, do not communicate to doctoral students effectively, do not provide clear feedbacks, and do not use the dissertation checklist that is required by their school. The researchers provided some implications for practice and some conclusions.
Site-Selective Antibody Functionalization via Orthogonally Reactive Arginine and Lysine Residues

Homogeneous antibody-drug conjugates (ADCs) that use a highly reactive buried lysine (Lys) residue embedded in a dual variable domain (DVD)-IgG1 format can be assembled with high precision and efficiency under mild conditions. Here we show that replacing the Lys with an arginine (Arg) residue affords an orthogonal ADC assembly that is site-selective and stable. X-ray crystallography confirmed the location of the reactive Arg residue at the bottom of a deep pocket. As the Lys-to-Arg mutation is confined to a single residue in the heavy chain of the DVD-IgG1, heterodimeric assemblies that combine a buried Lys in one arm, a buried Arg in the other arm, and identical light chains, are readily assembled. Furthermore, the orthogonal conjugation chemistry enables the loading of heterodimeric DVD-IgG1s with two different cargos in a one-pot reaction and thus affords a convenient platform for dual-warhead ADCs and other multifaceted antibody conjugates.
How to say "no" most effectively: Evaluating resistance strategies for prescription stimulant diversion to inform preventive interventions.

We evaluated the perceived effectiveness of resistance strategies students could employ if approached to give away, trade, or sell their prescription stimulant medication, a growing concern on coll...
Expression of Ptn increases the areas of invasive scirrhous carcinoma in MMTV-PyMT transgenic mouse model of breast cancer

1774 Pleiotrophin (PTN, Ptn is the gene) is an 18 KDa heparin-binding cytokine. The Ptn gene is regulated both temporally and in cell type specificity during development but, in adults, Ptn gene expression is constitutive and limited to few cell types, except in inflammatory and endothelial cells in injured tissue and early tissue repair. The Ptn gene is an oncogene; Ptn expression is found in glioblastoma, breast cancer, melanoma and many other tumors. In these studies, we wished to identify the role of PTN in breast cancer. We generated transgenic mice in which the Ptn gene was driven by the mouse mammary tumor virus promoter (MMTV) and bred these mice with MMTV-Polyoma middle T (PyMT) gain of function breast cancer predisposition mice. The MMTV-Ptn gain of function mice breed and lactate normally and histological abnormalities in breast tissue have not been found. There is no significant difference in the onset of palpable tumors between MMTV-PyMT single transgenic mice and MMTV-PyMT/Ptn double transgenic mice; although the average tumor size in MMTV-PyMT/Ptn double transgenic mice was larger, the difference was not statistically significant. However, the morphological pattern of the MMTV-PyMT/Ptn double transgenic mice differed; we observed a significant increase of epithelial islands characteristic of invasive scirrhous carcinoma in areas within the tumor. The levels of expression of the Ptn gene were higher in these areas with a scirrhous carcinoma pattern. Furthermore, these areas were surrounded by collagen and elastin and increased numbers of new blood vessels were found in the microenvironment surrounding the tumors. Increased levels of activated ERK1/2 were found and the expression of ER1-46, the 46 KD isoform of Estrogen Receptor 1 that has lost the N-terminal estrogen-independent transactivation domain was also increased. These data support the conclusion that expression of Ptn initiates a significant switch to aggressive growth in MMTV-PyMT breast cancer in mice.
Minority Commercial Radio Ownership in 2009: FCC Licensing and Consolidation Policies, Entry Windows, and the Nexus between Ownership, Diversity and Service in the Public Interest

This study examines more than 11,000 records from the Federal Communications Commission’s (FCC) Consolidated Database System (CDBS) and Internet sources on radio ownership and program formats in mid-2009 to analyze the effect of FCC licensing and multiple ownership policies on minority ownership of commercial radio stations, program diversification, and service to the American public. This analysis is timely and important as the FCC prepares for its quadrennial review of broadcasting rules in 2010, mandated by the Telecommunications Act of 1996 (§202(h)). Analyzing media ownership is critical because "[i]t is upon ownership that public policy places primarily reliance with respect to diversification of content, and that has proven to be significantly influential with respect to editorial comment and the presentation of news." TV9 Inc. v. FCC, 495 F.2d 929 (D.C. Cir. 1974), cert. denied, 419 U.S. 986 (1974). This study’s finds that in 2009, 74.7% of minority commercial radio broadcasters air minority-oriented programming, demonstrating a robust nexus between ownership and program diversity. While the Internet is growing, 90% of all Americans still rely on radio each week for news and entertainment programming that facilitates our democratic dialogue.This study finds that 324 minority owners control 815 commercial radio stations in 2009. It examines factors affecting entry into broadcasting including the FCC’s licensing and consolidation policies. It finds that fifty-three percent of minority commercial radio broadcasters in 2009 were awarded their first license among the radio station licenses they still control, prior to the Telecommunications Act of 1996, legislation which permitted a dramatic increase in radio ownership consolidation locally and nationally. This study recommends that the FCC consider these findings in its 2010 examination of broadcast rules, and simultaneously examine its auction rules used to assign broadcast construction permits. This study emphasizes the imperative of the FCC improving its database to identify and facilitate analysis of broadcast ownership trends including the increasing number of stations going dark for financial reasons, bankruptcies, liquidations, and lender workouts in light of the recession and shift to Internet advertising.
Optimizing Neuromodulation Testing—Who, When, and How?

We review the current literature pertaining to recommendations for selecting appropriate patients and performing a test phase for sacral neuromodulation. Current literature reveals that this therapy can be successfully offered to patients with mild and severe forms of refractory overactive bladder, wet or dry. It can also be offered to elderly patients and patients with concurrent fecal incontinence, even in the setting of a known history of obstetric anal sphincter injury. Patients with non-obstructive urinary retention should be carefully selected with other etiologies ruled out, and an emphasis on those patients with suspected Fowler’s syndrome. We also summarize the recommendations for ideal lead placement and the advantages/disadvantages of a percutaneous nerve evaluation in the office compared to a staged procedure. The use of sacral neuromodulation for bladder dysfunction has evolved over the years. Patient selection and testing technique is an important component in optimizing the success of this therapy.
Hidden musicality in Chinese Xiangsheng: a response to the call for interdisciplinary research in studying speech and song

Recent scholarship in the field of music cognition suggests the need for increased interdisciplinarity in moving beyond the boundaries of Western European music, and the study of the relationship between language and music is an especially fruitful area that can benefit from interdisciplinary collaboration. This paper heeds the call for collaborative research in cultures outside of Western Europe by focusing on Xiangsheng, a form of Chinese musical comedy that features an intriguing relationship between speech and song in performance. The present paper argues that analytical tools and perspectives from conversational analysis, communicative musicality, empirical research on music-language relationships, and performative mutuality in ethnomusicology all speak to the idea of musicality—the underlying capacity that undergirds our ability to communicate both verbally and musically—as a common foundational behavior in both speech and song. Musicality is particularly apparent in the way Chinese Xiangcheng actors relate to each other and their audiences in both spoken and musical modalities, and this paper suggests how judiciously employing a variety of methodological approaches in the study of musicality can yield important insights for researchers from all disciplines.
Publishing Characteristics of Foot and Ankle Research Over a 15-Year Time Interval: A Review of The Journal of Bone & Joint Surgery from 2004 to 2018.

Background As the foot and ankle subspecialty continues to grow in orthopaedics, trends in published literature provide valuable insights to help understand and strengthen the field. The current study evaluates the changes in the characteristics of foot and ankle articles in The Journal of Bone & Joint Surgery (American Volume) (JBJS-A) from 2004 to 2018. Methods Foot and ankle-related articles in JBJS-A from 2004 to 2018 were identified and categorized by type of study, level of evidence, number of authors, academic degree(s) of the first and last authors, male and female authorship, number of citations, number of references, region of publication, and use of patient-reported outcomes (PROs). Results A total of 336 foot and ankle articles from 2004 to 2018 were reviewed. The type of study published has changed over time, with more clinical therapeutic evidence and less case reports. The level of evidence grades, as rated by JBJS-A and objective evaluators, have increased over the past 15 years. The total number of authors per article has increased, and female authorship has increased significantly. The number of references per article has increased, and the number of citations per year has decreased. The field of foot and ankle surgery has seen an increase in global publications. Conclusions The results of this study suggest that the foot and ankle literature that has been published in JBJS-A has continued to increase in quality and diversity over the past 15 years.
Message-passing neural networks for high-throughput polymer screening

Machine learning methods have shown promise in predicting molecular properties, and given sufficient training data, machine learning approaches can enable rapid high-throughput virtual screening of large libraries of compounds. Graph-based neural network architectures have emerged in recent years as the most successful approach for predictions based on molecular structure and have consistently achieved the best performance on benchmark quantum chemical datasets. However, these models have typically required optimized 3D structural information for the molecule to achieve the highest accuracy. These 3D geometries are costly to compute for high levels of theory, limiting the applicability and practicality of machine learning methods in high-throughput screening applications. In this study, we present a new database of candidate molecules for organic photovoltaic applications, comprising approximately 91 000 unique chemical structures. Compared to existing datasets, this dataset contains substantially larger molecules (up to 200 atoms) as well as extrapolated properties for long polymer chains. We show that message-passing neural networks trained with and without 3D structural information for these molecules achieve similar accuracy, comparable to state-of-the-art methods on existing benchmark datasets. These results therefore emphasize that for larger molecules with practical applications, near-optimal prediction results can be obtained without using optimized 3D geometry as an input. We further show that learned molecular representations can be leveraged to reduce the training data required to transfer predictions to a new density functional theory functional.
Opening the Black Box of Solitary Confinement Through Researcher–Practitioner Collaboration: A Longitudinal Analysis of Prisoner and Solitary Populations in Washington state, 2002–2017

This article presents a rare longitudinal analysis of solitary confinement use in one state prison system: spanning 2002–2017 in the Washington Department of Corrections (DOC). An ongoing partnersh...
Through the eyes of a child: Sibling perspectives on having a sibling diagnosed with autism.

Abstract Background: Sibling perspectives on the experiences of families caring for an autistic child are often overlooked in autism research. While qualitative research on these lived experiences has grown, it continues to primarily focus on parent reports. Aims: This study explored how having a sibling with autism impacts the non-autistic siblings within a family systems framework. The goal of the current study was to expand the literature by exploring the impacts of autism on the sibling subsystem as reported by the parents and the non-autistic siblings themselves. Methods and Procedures: The researchers interviewed 15 non-autistic siblings (aged 7−17) and 15 parents of children with autism to understand the experience of growing up with a sibling with autism. Content analysis was used to develop the interview protocol and analyze responses. Parent and non-autistic sibling reports of both siblings' effects on each other's development are triangulated with existing research. Results: Findings indicate novel emotional skill-building occurs in non-autistic siblings, as well as some unique risk factors for internalizing and externalizing problems if non-autistic siblings' needs become deprioritized. Family stress, external relationships, intrapersonal and social skill development, and other implications of this unique relationship are discussed.
A qualitative investigation of the impact of coronavirus disease 2019 (COVID-19) on emergency physicians' emotional experiences and coping strategies.

Study objective: Throughout the coronavirus disease 2019 (COVID-19) pandemic, emergency physicians in the United States have faced unprecedented challenges, risks, and uncertainty while caring for patients in an already vulnerable healthcare system. As such, the pandemic has exacerbated high levels of negative emotions and burnout among emergency physicians, but little systematic qualitative work has documented these phenomena. The purpose of this qualitative investigation was to study emergency physicians' emotional experiences in response to COVID-19 and the coping strategies that they employed to navigate the pandemic. Methods: From September 2020 to February 2021, we conducted semistructured interviews with 26 emergency physicians recruited from 2 early COVID-19 epicenters: New York City and the Metro Boston region. Interviews, coding, and analyses were conducted using a grounded theory approach. Results: Emergency physicians reported heightened anxiety, empathy, sadness, frustration, and anger during the pandemic. Physicians frequently attributed feelings of anxiety to medical uncertainty around the COVID-19 virus, personal risk of contracting the virus and transmitting it to family members, the emergency environment, and resource availability. Emergency physicians also discussed the emotional effects of policies prohibiting patients' family members from entering the emergency department (ED), both on themselves and patients. Sources of physician anger and frustration included changing policies and rules, hospital leadership and administration, and pay cuts. Some physicians described an evolving, ongoing coping process in response to the pandemic, and most identified collective discussion and processing within the emergency medicine community as an effective coping strategy. Conclusions: Our findings underscore the need to investigate the effects of physicians' pandemic-related emotional stress and burnout on patient care. Evidence-based interventions to support emergency physicians in coping with pandemic-related trauma are needed.
From Metaphor to Theology

Theological change suffers under the obligation to seem—and the danger of seeming—both consistent with what has come before and genuinely new. Where does the idea of the suffering servant in Isaiah 53 come from? Leaving aside those acts of warfare and violence against the innocent, which seem more matters of brute aggression than symbolic atonement, we can find well-acknowledged roots for the doctrine of a suffering servant in the practice of symbolic animal sacrifice and in the figure of the prophet who suffers with, and perhaps for, the people. But there is a third root as well that goes back to the language of the divine attributes and to the ambiguous Hebrew idiom of noseh avon, bearing sin or forgiving sin. If the servant of God bears iniquity, he can be imagined not just to remove sin from the head or shoulders of many but also to carry what he removes; he himself can “bear” it. And when all the people in the Gospel of Matthew call down the blood of Jesus on their heads, they “own” (own up to, but also claim for their own) the rich history of ambiguous responsibility and atonement.
The Value of Cooperative Education

(1991). The Value of Cooperative Education. Hospitality & Tourism Educator: Vol. 4, No. 1, pp. 31-64.
Nigrostriatal lesions alter oral dyskinesia and c-Fos expression induced by the serotonin agonist 1-(m-chlorophenyl)piperazine in adult rats.

The loss of dopaminergic innervation of the basal ganglia, a group of subcortical regions involved in motor control, is the hallmark of Parkinson's disease. The resulting molecular and cellular alterations mediate behavioral deficits and may modify neuronal responses to other neurotransmitters. In the present study, we sought to determine the effects of chronic dopamine (DA) depletion on responses mediated by stimulation of serotonergic 2C (5-HT2C) receptors, a serotonergic receptor subtype present in discrete regions of the basal ganglia. Specifically, the effects of unilateral lesions of nigrostriatal DA neurons on oral dyskinesia and Fos protein expression induced by the non-selective 5-HT2C agonist 1-( m -chlorophenyl)piperazine ( m- CPP) were examined. Confirming previous findings, both peripheral and local injections of m -CPP into the subthalamic nucleus elicited oral dyskinesia. Nigrostriatal lesions markedly enhanced oral bouts induced by peripheral but not intrasubthalamic administration of m -CPP. In intact rats, Fos expression was increased by m- CPP (1 mg/kg, i.p.) in the striatum and the subthalamic nucleus. After nigrostriatal lesions, m -CPP-induced Fos expression remained unchanged in the subthalamic nucleus but was reduced in the medial quadrants of the striatum and was markedly enhanced in the entopeduncular nucleus. These data demonstrate regionally specific alterations in behavioral and cellular responses to a serotonergic agonist in an animal model of Parkinson's disease.
Facework on Facebook: How it legitimizes community membership and enables linguistic socialization through intertextuality

Thesis (M.S.)--Georgetown University, 2010.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. This study uses Facebook conversations as a new domain to explore the intersection of facework and intertextuality in computer-mediated social discourse. Looking closely at how members of an older generation are being socialized to the norms of a younger generation-dominated space, there is evidence that members use local texts to create a shared repertoire of "prior texts" in order to narrate something about the self and create a sense of in-group, maintaining positive face and building a community online.
Biosynthesis of glucans in mung bean seedlings. Formation of beta-(1,4)-glucans from GDP-glucose and beta-(1,3)-glucans from UDP-glucose

A particulate enzyme system from Phaseolus aureus catalyzed the incorporation of radioactivity from UDP-glucose-14C and GDP-glucose-14C into alkali-soluble and alkali-insoluble polysaccharides. Most (90%) of the radioactivity incorporated from UDP-glucose-14C was in the water-insoluble, alkali-soluble polymers while the remaining 10% was in the alkali-insoluble fraction. On the other hand, most (60–90%) of the 14C incorporated from GDP-glucose-14C remained in the alkali-insoluble polysaccharides. The incorporation of both UDP-glucose-14C and GDP-glucose-14C into the alkali-soluble and alkali-insoluble materials reached a maximum in 1 to 2 min and then leveled off, but incorporation of both nucleotides was linear with protein concentration. The radioactive, alkali-insoluble polysaccharides synthesized from both UDP-glucose-14C and GDP-glucose-14C were compared by various criteria to determine the nature of the polymers and of their glycosidic linkages. Acetolysis or partial acid hydrolysis of the GDP-glucose-14C synthesized product gave rise to cellobiose as the only 14C-disaccharide whereas the product formed from UDP-glucose-14C produced mostly laminaribiose (β, 1 → 3). Periodate oxidation of either the larger oligosaccharides or the insoluble polymer formed from GDP-glucose-14C, followed by reduction and hydrolysis, led to the formation of 14C-erythritol, confirming a 1 → 4 linkage. On the other hand, periodate oxidation of the UDP-glucose-14C products under identical conditions produced mostly 14C-glucose, further suggesting a 1 → 3 linkage. The alkali-soluble polymers produced from UDP-glucose-14C were identical to the alkali-insoluble polysaccharide on the basis of acetolysis and periodate oxidation. Treatment of the particles with digitonin resulted in their loss in the ability to incorporate radioactivity from UDP-glucose-14C and GDP-glucose-14C into polysaccharides. However, 70% of the activity with GDP-glucose-14C, but virtually none of the UDP-glucose-14C activity, was restored by adding 7 × 10−3m Mg2+ to the particles. The UDP-glucose-14C polysaccharide synthesizing activity was found in the digitonin-treated supernatant liquid. This soluble enzyme fraction catalyzed the incorporation of radioactivity from UDP-glucose-14C into a water-insoluble polysaccharide which had the properties of aβ-(1 → 3)-glucan. Radioactive laminaribiose and smaller amounts of laminaritriose and laminaritetraose were also formed by the soluble enzyme.
Combining regional moist static energy and ENSO for forecasting of early and late season Indian monsoon rainfall and its extremes

We exploit El Nino–Southern Oscillation (ENSO) indices and moist static energy of surface air over the Indian subcontinent and surroundings as predictors of monsoon rainfall over India during early and late seasons, defined here as 20 May to 15 June and 20 September to 15 October, respectively. Although these seasons contribute only ~22% of the entire seasonal rainfall, they clearly affect planning of agriculture and water resources. A simple, nonlinear, statistical model applied to these predictors accounts for ~40% and 45% of the observed variance of early and late season rainfall, respectively, and similar fractions for 3 day maximum rainfall intensity. Forecasted average and 3 day maximum rainfall at grid points covering India show greatest success over central India during the early season and over west central, northwestern, and northern India during the late season, regions where agriculture dominates land use. These predictors, however, offer virtually no predictability of peak season rainfall.
Protein Folding: Energetics

The energetics of protein folding determine how the amino acid sequence of a protein is constrained to fold into its correct three-dimensional structure. Thus, knowledge of the folding energetics is needed to predict protein structure from sequence or to modify sequence and structure by protein engineering. The traditional approach to folding energetics, which emphasizes major factors, is followed here. This article discusses chiefly three major factors: the hydrophobic factor, peptide hydrogen bonds/peptide solvation, and backbone conformational entropy. Auxiliary factors, such as van der Waals interactions, disulfide bonds, salt bridges, and helix propensities, are discussed briefly.
Role of corticosterone in modulation of eicosanoid biosynthesis and antiinflammatory activity by 5-lipoxygenase (5-LO) and cyclooxygenase (CO) inhibitors.

The effectiveness of 5-lipoxygenase (LO) and dual LO/cyclooxygenase (CO) inhibitors when administered by the topical or oral routes was significantly decreased in corticosterone depleted (adrenalectomized, Adx) mice as compared to sham mice in the mouse arachidonic acid (AA) induced ear edema model. In contrast, rat carrageenan paw edema was inhibited similarly in sham and Adx animals by 5-LO and dual 5-LO/CO inhibitors. Supplementation of cortisol levels (100 μg/dl) in human whole blood for 2 hr increased the observed inhibition of LTB4 biosynthesis by A-64077, WY-50,295 tromethamine and naproxen while having no effect on thromboxane B2 (TXB2) biosynthesis. Thus, corticosteroids may have a permissive effect, by modulating 5-LO inhibitor, effects on mouse AA induced ear edema and human blood leukocytes.
Step tunneling enhanced asymmetry in metal-insulator-insulator-metal (MIIM) diodes for rectenna applications

We combine nanolaminate bilayer insulator tunnel barriers (Al2O3/HfO2, HfO2/Al2O3, Al2O3/ZrO2) deposited via atomic layer deposition (ALD) with asymmetric work function metal electrodes to produce MIIM diodes with enhanced I-V asymmetry and non-linearity. We show that the improvements in MIIM devices are due to step tunneling rather than resonant tunneling. We also investigate conduction processes as a function of temperature in MIM devices with Nb2O5 and Ta2O5 high electron affinity insulators. For both Nb2O5 and Ta2O5 insulators, the dominant conduction process is established as Schottky emission at small biases and Frenkel-Poole emission at large biases. The energy depth of the traps that dominate Frenkel-Poole emission in each material are estimated.
Hydrodynamically coupled rigid bodies

This paper considers a finite number of rigid bodies moving in potential flow. The dynamics of the solid--fluid system is described in terms of the solid variables only using Kirchhoff potentials. The equations of motion are first derived for the problem of two submerged bodies where one is forced into periodic oscillations. The hydrodynamic coupling causes the free body to drift away from or towards the oscillating body. The method of multiple scales is used to separate the slow drift from the fast response. Interestingly, the free body, when attracted towards the forced one, starts to drift away after it reaches certain separation distance. This suggests that the hydrodynamic coupling helps in preventing collisions. The fluid's role in collision avoidance and motion coordination is examined further through examples. In particular, we show that a free body can coordinate its motion with that of its neighbours, which may be relevant to understanding the coordinated motion in fish schooling.
Exercise interventions and peripheral arterial function: implications for cardio-metabolic disease

Physical inactivity is a major risk factor for the development of obesity and other cardiovascular (CV) disease (CVD). Vascular endothelial dysfunction is a key event in the development of CVD and is associated with a sedentary lifestyle in otherwise healthy adults. In addition, vascular endothelial dysfunction may be exacerbated in sedentary individuals who are obese and insulin resistant, since excess body fat is associated with elevated levels of pro-atherogenic inflammatory adipokines and cytokines that reduce the nitric oxide (NO) and other upstream paracrine signaling substances which reduces vascular health. Since blood flow-related shear stress is a major stimulus to NO release from the endothelium, disturbed flow or low shear stress is the likely mechanism by which vascular endothelial function is altered with inactivity. Evidence shows that regular physical exercise has beneficial effects on CVD and the risk factors that promote peripheral arterial function and health. Both aerobic and resistance exercise training are generally believed to improve endothelial function and are commonly recommended for CV health, including the management of obesity, hypertension, and insulin resistance. However, many factors including age, disease status, and race appear to influence these outcomes. Although evidence supporting the health benefits of exercise is compelling, the optimum prescription (volume and intensity) and the exact mechanism underlying the effects of exercise training on arterial function and cardiometabolic risk has yet to be identified. The focus of this review will be on the evidence supporting exercise interventions for peripheral arterial function.
THE EFFECTS OF RATE, SEQUENCING, AND MEMORY ON AUDITORY PROCESSING IN THE ELDERLY

Auditory sequencing, rate, and memory were evaluated in three age groups with a series of subtests that require the identification of tones (Repetition Test; Tallal & Piercy, 1973). The older elderly group (M age = 80), but not the younger elderly group (M age = 70), performed significantly (p less than .05) poorer than the young adult group (M age = 25) when auditory memory of 4 and 5 tones was required and when the interstimulus interval was decreased. Performance was not related to hearing sensitivity, thus suggesting that changes in the auditory mechanism that occur with age may encompass more than a loss of hearing sensitivity. Moreover, performance on the Repetition Test did correlate with memory for digits, which indicates a relationship between auditory processing and higher cortical functions.
The effect of mid-latitude electron precipitation on the geoelectric field

A simple model is outlined to describe electron precipitation from the population of charged particles trapped in the earth's magnetic field; almost all of the precipitation is shown to occur in the region of the South Atlantic Anomaly. When the effect of a dawn-to-dusk electric field across the magnetosphere is included in the model, a diurnal modulation of the precipitated electron flux is predicted. Experimental evidence which supports the diurnal modulation model is described.
Numerical Analysis of Flow Through a Severely Stenotic Carotid Artery Bifurcation

The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits. In this study, a model based on an endarterectomy specimen of the plaque in a carotid bifurcation was examined. The flow conditions include steady flow at Reynolds numbers of 300, 600, and 900 as well as unsteady, pulsatile flow. Both dynamic pressure and wall shear stress are very high, with shear values up to 70 N/m 2 , proximal to the stenosis throat in the internal carotid artery, and both vary significantly through the flow cycle. The wall shear stress gradient is also strong along the throat. Vortex shedding is observed downstream of the most severe occlusion. Two turbulence models, the Chien and Goldberg varieties of k-«, are tested and evaluated for their relevance in this geometry. The Chien model better captures phenomena such as vortex shedding. The flow distal to stenosis is likely transitional, so a model that captures both laminar and turbulent behavior is needed. @DOI: @10.1115/1.1427042#
Delayed therapy of experimental global cerebral ischemia with acetyl-l-carnitine in dogs

Acetyl-L-carnitine (ALCAR), when administered immediately following restoration of spontaneous circulation (ROSC) from experimental cardiac arrest (CA) has previously been demonstrated to promote normalization of brain energy metabolism and neurologic recovery following 10 min CA. In order to determine ultimate efficacy for this or other drugs, clinical trials must be performed in human subjects. In several human clinical trials, though, drug administration has been significantly delayed following resuscitation from CA. These experiments test the hypothesis that post-resuscitative delay in ALCAR administration will impair the ability of this drug to promote neurologic recovery. Neurological deficit scoring (23 h) as well as frontal cortex lactate levels (2 and 24 h) were compared following resuscitation from 10 min CA in dogs receiving either ALCAR or drug vehicle 30 min following ROSC. Dogs treated with ALCAR 30 min following ROSC from 10 min CA exhibited more normal cerebral cortex lactate levels than did vehicle control animals. There was no difference, however, in neurologic deficit scores between groups, with all animals demonstrating moderate to severe clinical neurologic impairment at 23 h following ROSC. A 30-min delay in ALCAR administration following ROSC from 10 min CA impairs the ability of this drug to promote neurologic recovery despite apparent normalization of brain lactate levels.
Site-directed mutagenesis to determine essential residues of ribulose-bisphosphate carboxylase of Rhodospirillum rubrum

Both Lys-166 and His-291 of ribulosebisphosphate carboxylase/oxygenase fromRhodospirillum rubrum have been implicated as the active-site residue that initiates catalysis. To decide between these two candidates, we resorted to site-directed mutagenesis to replace Lys-166 and His-291 with several amino acids. All 7 of the position-166 mutants tested are severely deficient in carboxylase activity, whereas the alanine and serine mutants at position 291 are ∼40% and ∼18% as active as the native carboxylase, essentially ruling out His-291 in theRhodospirillum rubrum carboxylase (and by inference His-298 in the spinach enzyme) as a catalytically essential residue. The ability of some of the mutant proteins to undergo carbamate formation or to bind either ribulosebisphosphate or a transition-state analogue remains largely unimpaired. This implies that Lys-166 is not required for substrate binding; rather, the results corroborate the earlier postulate that Lys-166 functions as an acid-base group in catalysis or in stabilizing a transition state in the reaction pathway.
Cognitive change checklist: psychometric characteristics in community-dwelling older adults.

Objective To extend the psychometric study of the Cognitive Change Checklist (3CL) by examining the reliability, factor structure, and external correlates of 3CL informant and self-report ratings in community-dwelling adults. We also conducted receiver operating characteristic analyses examining rating scores from this normative sample with those of clinical samples. Design Scale reliability and validity study. Setting Community sites. Participants Six hundred seventy-nine older adults. Results The pattern of scale relationships within and across versions, and the failure to find associations with age and education, were consistent with findings in clinic samples reported previously. Factor analysis replicated the four-factor structure of the informant ratings. All informant version scales significantly discriminated amnestic mild cognitive impairment cases and patients with mild dementia from normals. Conclusion These findings provide support for the use of the checklist as a clinical tool to facilitate identification of cases of mild cognitive impairment and early dementia.
Vaporization chemistry and thermodynamics in the CdGa2S4-Ga2S3 system

Abstract The chemistry and thermodynamics of vaporization of CdGa 2 S 4 ( s ), CdGa 8 S 13 ( s ), and Ga 2 S 3 ( s ) were studied by computer-automated, simultaneous Knudsen-effusion and torsion-effusion, vapor pressure measurements in the temperature range 967–1280 K. The vaporization was incongruent with loss of Cd(g) + 1/2 S 2 (g) and production of CdGa 8 S 13 ( s ), a previously unknown compound, in equilibrium with CdGa 2 S 4 ( s ), until the solid became CdGa 8 S 13 only. Then, incongruent vaporization continued with production of Ga 2 S 3 ( s ) until the solid was Ga 2 S 3 only. The latter vaporized congruently. The Δ H °(298 K) of combination of one mole of CdS( s ) with one mole of Ga 2 S 3 ( s ) to give CdGa 2 S 4 ( s ) was −22.6 ± 0.9 kJ mole −1 . The † H †(298 K) of combination of one mole of CdS( s ) with four moles of Ga 2 S 3 ( s ) to give CdGa 8 S 13 ( s ) was −25.5 ± 1.1 kJ mole −1 . The † H †(298K) of CdGa 8 S 13 ( s ) with respect to disproportionation into CdGa 2 S 4 ( s ) and 3 Ga 2 S 3 ( s ) was −2.8 ± 0.6 kJ mole −1 . CdGa 8 S 13 ( s ) was not observed at room temperature. The † H †(298 K) of vaporization of the residual Ga 2 S 3 ( s ) was 663.4 ± 0.8 kJ mole −1 , which compared well with a value of 661.4 ± 0.3 kJ mole −1 already available from the literature. Implications of small variations in stoichiometry of compounds in this study were observed and are discussed.
A comparative study of the effects of chronic administration of propoxyphene salts to normal volunteers.

Abstract Two salts of the oral analgesic agent propoxyphene, the hydrochloride salt and the 2-naphthylene sulfonic acid salt, were evaluated for safety in a 6-month study in normal male inmates of a penal institution. Parameters measured included subjective side effects, hematologic response, blood chemistry, and urine analysis as well as routine physical examination. There were 40 subjects in each drug group initially, and a concomitant control group of 40 subjects received placebo capsules for the duration of the study. There were no changes in any of the parameters measured which could be attributed to the drugs. An epidemic of mild, anicteric hepatitis did produce changes in liver function as measured by serum transaminases and alkaline phosphatase levels; however, these occurred with equal frequency in all 3 groups and were also observed in subjects not participating in the study. The results indicate the value of concomittant placebo controls in a study of this type.
New visualizations for radiation therapy treatment planning

SUMMARYHigh quality interactive 3D displays are not just pretty pictures, but are important for radiationtherapy treatment planning as they add content and understanding to simpler displays. Imagessuch as shown in Figures 1 -3 are of great dvalue in defining radiation beam placement and indetermining the accuracy of 3D image registration.REFERENCES[1] Sherouse GW,Chaney EL:The portable virtual simulator. mt. J. Radiat. Oncol. Biol. Phys.21:475482; 1991.[2] Sherouse GW, Novins K, Chaney EL: Computation of digitally reconstructed radiographsfor use in radiotherapy treatment design. mt J Radiat Oncol Biol Phys 18:651-658, 1990.[3] Cullip TJ, Symon JR, Rosenman JG, Chaney EL: Digitally reconstructed fluoroscopy andother interactive volume visualizations in 3-D treatment planning. mt J Radiat Oncol BiolPhysics, 27:145-151, 1993.[4] Siddon R: Fast calculation of the exact radiological path for a three-dimensional CT array.Med Phys 12:252-255, 1985.[5] Rosenman J, Soltys M, Cullip T, Chen J: Improving treatment planning accuracy throughmultiple modality imaging. mt J Radiat Oncol Biol Phys [In press]
Localizing Fatty Acid Binding Sites on Human Serum Albumin by 2D-NMR

The most abundant protein in plasma, human serum albumin (HSA), is the principal carrier for endogenous lipophilic compounds and lipophilic drugs. Non-esterified long chain fatty acids (FA) are its primary physiological ligand, with multiple binding sites of varying affinities. Detailed structural understandings of HSA-ligand interactions are vital during the development of drugs. HSA ligand interactions have been studied by various biophysical methods: x-ray crystallography, fluorescence spectroscopy, and nuclear magnetic resonance (NMR). Numerous crystal structures of HSA, with and without drugs and/or FAs, have been published. Compared to crystallography, our solution state NMR studies are focused on the more physiologically relevant state. Previously, we identified three high affinity and several low affinity FA binding sites on HSA by 1D-NMR at low resolution. Now, we are correlating crystallographic data with high-resolution 2D-NMR spectra of 13C-methyl-labeled oleic acid (OA). Our 2D-HSQC spectra show the 13C-methyl group of OA bound to HSA. The unique microenvironments that each methyl group experiences in the binding pockets gives rise to different NMR signals of varying intensities. These correspond to the different affinities that HSA has for OA, and our 2D-NMR spectra clearly differentiate the three highest affinity-binding sites from six lower affinity-binding sites. We have identified Sudlow's Drug Sites by utilizing the known FA competitors and Sudlow's site binders: warfarin and diazepam. By expanding this drug competition strategy with ibuprofen and diflunisal, we have identified additional FA binding sites. The highest affinity FA binding sites do not have known competitors and these sites are identified with the use of site-directed mutagenesis of HSA. In summary, we are reporting an approach for studying the interactions of FAs with HSA and FA-competitive drugs in a site-specific manner through the use of state-of-the-art 2D-NMR techniques.
Chemical-shift relaxation in multiple-pulse NMR

Expressions are derived which describe the relaxation rates of spin systems under multiple-pulse conditions where the randomly fluctuating interaction is the chemical-shift Hamiltonian. The multiple-pulse schemes include the REV-8 pulse cycle and two “chemical-shift-concertina” cycles. One of these is the phase-alternated sequence, and the other is a new cycle consisting of four π pulses which more effectively suppresses lineshape artifacts resulting from rf inhomogeneity and other pulse imperfections. The calculated relaxation rates are used to predict lineshapes of chemical-shift spectra obtained from multiple-pulse experiments. A general discussion is presented in which T1 and T2 types of relaxations, anomalous T2 behavior when the correlation time is comparable to the cycle time, and chemical-shift scaling factors are related in a simple physical description. The theoretical predictions are shown to agree with experimental results obtained in the chemically exchanging liquid system of PF3Br2. These experiments include temperature-dependent lineshapes obtained by Fourier transform NMR, REV-8, and four-π pulse chemical-shift concertina (scaling factor, 0.18), as well as REV-8 relaxation times.
Possible direct cloud-to-ionosphere current evidenced by sprite-initiated secondary TLEs

[1] Video-rate images of sprites observed from Langmuir Laboratory show slow, upward discharges from the cloud to the mesosphere following the sprite discharge. A single high-time-resolution (1000 fps) measurement of the tip of the upward discharge shows that it terminates at the base of the preceding sprite and persists for a total of ∼50 ms, compared to the sprite lifetime of ∼6 ms. Photometer data show that these events are likely to be predominantly blue. We propose a mechanism by which, in conjunction with intra-cloud activity following the causative CG discharge, charge is moved within the sprite body from the ionosphere to the lower altitude edge of the sprite at ∼50 km; this transfer of charge lowers the upper capacitive plate, whereupon a second breakdown is facilitated between the cloud-top and this charged plate, inducing electrical current between the cloud and the mesosphere and initiating the observed luminous discharges.
Predicting mothers' compliance with pediatric medical regimens.

Mothers' adherence to medical instructions concerning their children is typically very inadequate, especially for episodes of acute illness. This study tests a new, behavioral model which employs mothers' health motivations, perceptions, and attitudes as predictors of giving oral penicillin and keeping follow-up appointments for otitis media. Variables in each model category were found to have useful explanatory and predictive value. The findings offer clues to identification of potential noncompliers and suggest particular psychological attributes of the mother which the pediatrician can influence to increase the likelihood of compliance.
THE EXTENSIBLE DEPENDENCY ANALYSIS TOOL SET: A KNOWLEDGE BASE FOR UNDERSTANDING INDUSTRIAL SOFTWARE

Industrial software systems are generally both large and complex. They tend to contain multiple languages and diverse kinds of structure that maintainers need to understand to do their jobs effectively. The Extensible Dependency Analysis Tool Set (EDATS) has been designed to provide support for understanding these kinds of systems. The EDATS concept emerged from discussions with industrial affiliates of the Software Engineering Research Center. It is built around a very flexible underlying structure in which software is represented as a generalized dependency graph; queries “by example” request chains of links from that graph. Information from diverse sources can be incorporated and the tool set can be easily extended to handle special relationships found in a particular system. A small case study is presented to illustrate the kinds of questions that maintainers tend to ask in understanding an unfamiliar system and to show how EDATS can help in answering such questions.