cssi/SciSciGPT-SciSciNet huggingface dataset:
A thermodynamically-constrained mathematical model for the kinetics and regulation of NADPH oxidase 2 complex-mediated electron transfer and superoxide production

Reactive oxygen species (ROS) play an important role in cell signaling, growth, and immunity. However, when produced in excess, they are toxic to the cell and lead to premature aging and a myriad of pathologies, including cardiovascular and renal diseases. A major source of ROS in many cells is the family of NADPH oxidase (NOX), comprising of membrane and cytosolic components. NOX2 is among the most widely expressed and well-studied NOX isoform. Although details on the NOX2 structure, its assembly and activation, and ROS production are well elucidated experimentally, there is a lack of a quantitative and integrative understanding of the kinetics of NOX2 complex, and the various factors such as pH, inhibitory drugs, and temperature that regulate the activity of this oxidase. To this end, we have developed here a thermodynamically-constrained mathematical model for the kinetics and regulation of NOX2 complex based on diverse published experimental data on the NOX2 complex function in cell-free and cell-based assay systems. The model incorporates (i) thermodynamics of electron transfer from NADPH to O2 through different redox centers of the NOX2 complex, (ii) dependence of the NOX2 complex activity upon pH and temperature variations, and (iii) distinct inhibitory effects of different drugs on the NOX2 complex activity. The model provides the first quantitative and integrated understanding of the kinetics and regulation of NOX2 complex, enabling simulation of diverse experimental data. The model also provides several novel insights into the NOX2 complex function, including alkaline pH-dependent inhibition of the NOX2 complex activity by its reaction product NADP+. The model provides a mechanistic framework for investigating the critical role of NOX2 complex in ROS production and its regulation of diverse cellular functions in health and disease. Specifically, the model enables examining the effects of specific targeting of various enzymatic sources of pathological ROS which could overcome the limitations of pharmacological efforts aimed at scavenging ROS which has resulted in poor outcomes of antioxidant therapies in clinical studies.
Outcome analysis of chemotherapy duration for resected stage I-II and unresected stage III pancreatic cancer.

375Background: For resected early-stage pancreatic cancer, RTOG 9704 has evaluated the outcome of 3 weeks of adjuvant chemotherapy (C) followed by chemoradiation (CRT) and post-CRT C. For locally a...
Do Cytotypes of Black Flies of the Simulium arcticum Complex (Diptera: Simuliidae) Arise from Sibling Species?

To better understand the evolutionary radiation of the Simulium arcticum complex of black flies (Diptera: Simuliidae), we compared the geographic distributions of present-day larvae to their sex-chromosome diversity. We used the 5 known data sets including collections and sex-chromosome analysis from 307 geographic locations of 31 taxa of approximately 20,000 larvae from throughout the geographic range of distribution of the complex, from Alaska, western Canada, and the western United States to southern California, Arizona, and New Mexico. Siblings (reproductively isolated in sympatry) have considerably larger geographic distributions than do cytotypes (not reproductively isolated in sympatry), suggesting that the former may have been in existence longer than the latter. Simulium negativum (the oldest member of the complex), S. brevicercum (standard noninverted sex chromosomes), S. saxosum (sex determination on the X chromosome), and S. arcticum s. s. (IIL-3) share geographic distributions with all other siblings. Notably, 21 of 22 cytotypes share geographic distributions within those of siblings. Cytotypes are almost always discovered within the geographic distributions of siblings, suggesting that the former might be arising sympatrically.
The DePaul Symptom Questionnaire-2: A Validation Study

Background: The DePaul Symptom Questionnaire (DSQ) was developed to assess the symptomatology and case definition fulfillment of individuals with myalgic encephalomyelitis (ME) and chronic fatigue ...
Retropharyngeal ectopic parathyroid adenoma versus lymph node: Problem solving with CT neck angiogram

A 66-year-old female underwent preoperative evaluation for primary hyperparathyroidism. Ultrasound (US) neck and technetium (Tc)-99m-sestamibi planar scintigraphy were negative, but single photon emission computed tomography/computed tomography (SPECT/CT) demonstrated a tracer-avid retropharyngeal nodule compatible with parathyroid adenoma (PTA). A retrospective review of CT neck angiogram (CTA) and neck magnetic resonance imaging (MRI) performed 4 months earlier for stroke evaluation revealed arterial phase hyperenhancing retropharyngeal tissue, which had been dismissed as a nonpathological lymph node. "Polar vessel sign" seen in two-thirds of PTA was also present on retrospective review of the CTA. The concordant findings between SPECT/CT and CTA were indicative of a solitary undescended ectopic PTA in the retropharyngeal space, an uncommon location. A successful surgical cure was achieved after minimally invasive parathyroidectomy. This case highlights the retropharyngeal space as an important ectopic site of PTA, limitation of US, and Tc-99m-sestamibi planar scintigraphy in identifying retropharyngeal PTA. We also discuss the role of CT and MRI and the challenge in differentiating retropharyngeal PTA from a lymph node.
Cultivar mixtures of soybeans have inconsistent effects on herbivore and natural-enemy populations

Abstract Mounting evidence suggests that increasing within-species (or genotypic) crop diversity by planting mixtures of cultivars is a promising tactic for managing herbivorous pests. The soybean aphid (Aphis glycines Matsumura) is an invasive species that has forced growers to increase use of insecticides across the Midwestern United States. There is a clear need for alternative and more sustainable management methods; therefore, the soybean-soybean aphid system provides a useful model for testing the utility of cultivar mixtures. We conducted a two-year field experiment with soybeans and soybean aphid to measure top-down and bottom-up ecological consequences of increasing plant genotypic diversity in crop fields. Soybean aphid populations can be suppressed by predators, but can also be influenced by aphid-tending ants. Specifically, we evaluated if cultivar mixtures influence soybean aphid populations, the associated arthropod community, predation, and crop yield. We compared monocultures of six soybean cultivars to all six possible five-cultivar mixtures using 82.8 m2 plots. We also assessed if cultivar mixtures influence populations of another herbivore, potato leafhopper. Separately for day and nighttime, we evaluated predator and ant populations, and measured predation. We also assessed soybean yield. Over the course of the study, aphid populations remained low, and cultivar mixtures did not alter season-long aphid pressure or yield, but did produce intermediate yield and aphid populations compared to monocultures. Crop genotypic diversity increased leafhopper populations, likely because of non-additive interactions involving one highly susceptible or attractive cultivar. Diversity did not influence aphid-tending ants. In both years, predators helped suppress aphid populations, and predator abundance and predation was influenced by genotypic diversity during specific parts of the season and for some sampling times, but results were mixed and inconsistent. Of the most abundant taxa, genotypic diversity increased abundance of Harmonia axyridis in 2010 during the day, but not the night. Overall, results from this study demonstrated that under low pest pressure, cultivar mixtures do not produce clear benefits. Mixtures did appear to produce intermediate aphid populations and yield, and also influenced other herbivore species, which could influence natural-enemy control of soybean aphids. Effects on herbivores and predators could become more important under high pest pressure, although this remains to be determined. Our study also provides some evidence that plant genotypic diversity in crop fields can influence higher trophic levels, paralleling work in natural systems that has demonstrated system-wide consequences of diversity.
Teachers Bridging the Digital Divide in Rural Schools with 1:1 Computing

This article shares the findings of a mixed method study about the implementation of 1:1 computing in a small rural Florida school district. Researchers used multiple regression analyses to examine whether Davis’ (1989) Technology Acceptance Model helped explain teachers’ adoption of 1:1. The results indicated that the rural teachers’ perceived ease of use and perceived usefulness of 1:1 were significant predictors of both whole class and individualized instructions with 1:1. The qualitative phase of the study explored the ways in which the teachers integrated 1:1 into their instructional practices and what factors motivated them to do so. The analysis showed that the teachers used 1:1 largely to foster digital literacy and collaboration as well as to conduct student assessment. Reasons why the teachers integrated 1:1 into instruction included increasing student engagement, personalizing learning, and facilitating teacher productivity.
Do social contacts improve the mental health of middle-aged and older adults in China?

This paper aims to investigate how social contacts affect middle-aged and older adults’ (MOA) mental health, happiness, depression, and loneliness in China. The results show that social relations lead to an improvement of mental health and happiness and relief of depression and loneliness. For respondents who changed the status of their social contacts during the sample period, social relations benefit overall mental health and happiness but have no significant impact on depression and loneliness. Moreover, the loss in mental health and happiness from quitting the social activities exceeds the gain from joining. This asymmetrical impact between adding and dropping social contacts emphasizes the importance of maintaining the social relations of current participants. On average, the MOA’s willingness to pay (WTP) for social contacts ranges from $235 to $270, or 9.57–11.00% of income a year.
Prenatal Diagnosis of Isolated Atrioventricular Discordance and Ventriculoarterial Concordance and Double-Outlet Right Ventricle in Situs Inversus: Case Report and Review of the Literature

Atrioventricular (AV) discordance and ventriculoarterial (VA) concordance in the setting of visceral situs inversus are one of the rarest forms of cardiac malformations. To our knowledge, this is the first reported case of prenatal diagnosis of such rare cardiac anatomy in association with double-outlet right ventricle on fetal echocardiography. The physiology of this cardiac anomaly is similar to that of transposition of the great arteries, and the best surgical option is the atrial switch operation.
Regional Brain Biometrics at Term-Equivalent Age and Developmental Outcome in Extremely Low-Birth-Weight Infants.

Objective This study aims to evaluate individual regional brain biometrics and their association with developmental outcome in extremely low-birth-weight (ELBW) infants. Study Design This is a retrospective study evaluating term-equivalent magnetic resonance imaging (TE-MRI) from 27 ELBW infants with known developmental outcomes beyond 12 months corrected age. Regional biometric measurements were performed by a pediatric neuroradiologist blinded to outcome data. Measures included biparietal width, transcerebellar diameter (TCD), deep gray matter area (DGMA), ventricular dilatation, corpus callosum, and interhemispheric distance. The relationship between regional biometrics and Bayley-II developmental scores were evaluated with linear regression models. Results The study cohort had an average ± standard deviation birth weight of 684 ± 150 g, gestational age of 24.6 ± 2 weeks and 48% males. DGMA was significantly associated with both cognitive and motor outcomes. Significant associations were also observed between TCD and corpus callosum splenium with cognitive and motor outcomes, respectively. Other biometric measures were not associated with outcome ( p > 0.05). DGMA 2 was highly specific for poor motor and cognitive outcome. Conclusion TE-MRI biometrics reflecting impaired deep gray matter, callosal, and cerebellar size is associated with worse early childhood cognitive and motor outcomes. DGMA may be the most robust single biometric measure to predict adverse developmental outcome in preterm survivors.
Editorial: Toward Neurobiological-based Treatments of Depression and Anxiety: A Potential Case for the Nucleus Accumbens.

Depression and anxiety disorders together account for the majority of mental health disorders in childhood and adolescence, and are often comorbid.1 The frequent co-occurrence of these disorders has motivated clinicians and researchers to consider dimensional taxonomy models that focus on neurobiological substrates that explain transdiagnostic constructs of functioning (eg, reward processing abnormalities). Such an approach would redefine not only depression and anxiety disorders but could also revolutionize clinical care, as such biobehavioral targets, rather than a traditional primary diagnosis, could serve as the basis for treatment planning. In this issue of the Journal, Auerbach et al.2 examined whether and how a key structure involved in reward processing, the nucleus accumbens (NAcc), is altered in adolescents aged 14 to 17 years with depression and/or anxiety (including generalized anxiety, separation anxiety, social anxiety, specific phobia, agoraphobia, and panic) disorders, and whether NAcc morphometry and function would improve prediction of 6-month symptomatology. As part of the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) initiative,3 the researchers compared 129 adolescents with primary diagnoses of depression and/or anxiety and 64 psychiatrically healthy controls on gray matter volumes of the NAcc and on functional activation of the NAcc during a monetary incentive delay task using magnetic resonance imaging (MRI) protocols harmonized with the Human Connectome project (http://www.humanconnectomeproject.com/). Compared to healthy adolescents, depressed/anxious adolescents exhibited significantly smaller volumes of the NAcc and blunted NAcc responses to reward receipt. Among the 88 depressed/anxious adolescents and 57 healthy controls who provided symptom data 6 months later, the researchers also found that inclusion of NAcc volumes, but not reward-related responses of the NAcc on the task, significantly improved statistical prediction of subsequent depression symptoms.
The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

Cell identity is characterized by a distinct combination of gene expression, cell morphology and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in later larval stage and adult worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.
Clinical Decision Support: Elements of a Sensible Legal Framework

Clinical decision support (“CDS”) systems are computer programs that are designed to assist patients and health care professionals. A key segment of the CDS market encompasses software that utilizes sophisticated algorithms that combine biomedical knowledge, clinical practice guidelines, and patient-specific data to offer treatment recommendations for individual patients. If developed and used properly, such software can enhance health care decision-making, reduce health care costs, and improve health outcomes. Yet, the quality of CDS programs varies considerably, and CDS recommendations have led to medical errors and adverse health events. This article examines the legal and regulatory landscape governing CDS. I begin by unpacking the regulatory regime and analyzing regulatory ambiguities. I then highlight the limits of regulation, and discuss the proper role of tort law for CDS-related harms. I conclude by arguing that, when structured sensibly, laws and regulations can serve as important levers that incentivize safe and effective CDS systems.
Dodge v. Ford: What Happened and Why?

Behind Henry Ford’s business decisions that led to the widely taught, famous-in-law-school Dodge v. Ford shareholder primacy decision were three industrial organization structures that put Ford in a difficult business position. First, Ford Motor had a highly profitable monopoly and needed much cash for the just-begun construction of the River Rouge factory, which was said to be the world’s largest when completed. Second, to stymie union organizers and to motivate his new assembly-line workers, Henry Ford raised worker pay greatly; Ford could not maintain his monopoly without sufficient worker buy-in. And, third, if Ford explicitly justified his acts as in pursuit of the monopoly profit in the litigation, the Ford brand would have been damaged with both his workforce and the car buyers. The transactions underlying Dodge v. Ford and resulting in the court order that a very large dividend be paid should be reconceptualized as Ford Motor Company and its auto workers splitting the “monopoly rectangle” that Ford Motor’s assembly line produced, with Ford’s business requiring tremendous cash expenditures to keep and expand that monopoly. Hence, a common interpretation of the litigation setting—that Ford let slip his charitable purpose when he could have won with a business judgment defense—should be reconsidered. Ford had a true business purpose to cutting back the dividend—spending on labor and a vertically integrated factory to solidify his monopoly and splitting the monopoly profit with labor—but he would have jeopardized the strategy’s effectiveness by boldly articulating it. The existing main interpretations of the corporate law decision and its realpolitik remain relevant—such as Ford seeking to squeeze out the Dodge brothers by cutting the Ford dividend to deny the Dodge brothers cash for their own car company. But those interpretations must take a back seat, as none fully encompasses the industrial setting—of monopoly, incipient union organizing, and a restless workforce. Without accounting for Ford Motor’s monopoly, the River Rouge construction, and the related labor tensions, we cannot fully understand the Dodge v. Ford controversy. Stakeholder pressure can more readily succeed in a firm having significant economic rents, a setting that seems common today and was true for Ford Motor Company in the 1910s.
Electrophysiological- and Neuropharmacological-Based Benchmarking of Human Induced Pluripotent Stem Cell-Derived and Primary Rodent Neurons.

Human induced pluripotent stem cell (iPSC)-derived neurons are of interest for studying neurological disease mechanisms, developing potential therapies and deepening our understanding of the human nervous system. However, compared to an extensive history of practice with primary rodent neuron cultures, human iPSC-neurons still require more robust characterization of expression of neuronal receptors and ion channels and functional and predictive pharmacological responses. In this study, we differentiated human amniotic fluid-derived iPSCs into a mixed population of neurons (AF-iNs). Functional assessments were performed by evaluating electrophysiological (patch-clamp) properties and the effect of a panel of neuropharmacological agents on spontaneous activity (multi-electrode arrays; MEAs). These electrophysiological data were benchmarked relative to commercially sourced human iPSC-derived neurons (CNS.4U from Ncardia), primary human neurons (ScienCell™) and primary rodent cortical/hippocampal neurons. Patch-clamp whole-cell recordings showed that mature AF-iNs generated repetitive firing of action potentials in response to depolarizations, similar to that of primary rodent cortical/hippocampal neurons, with nearly half of the neurons displaying spontaneous post-synaptic currents. Immunochemical and MEA-based analyses indicated that AF-iNs were composed of functional glutamatergic excitatory and inhibitory GABAergic neurons. Principal component analysis of MEA data indicated that human AF-iN and rat neurons exhibited distinct pharmacological and electrophysiological properties. Collectively, this study establishes a necessary prerequisite for AF-iNs as a human neuron culture model suitable for pharmacological studies.
Developing a legal framework for energy storage technologies in the U.S: The case of pumped underground storage hydro

Abstract The Energy Act of 2020 authorizes $1 billion over five years from 2021 to 2025 to support energy storage development in the United States. In addition, the Federal Energy Regulatory Commission (FERC) Orders 841 and 2222 opened the wholesale energy markets for distributed energy resources, including energy storage. The statute and orders pave the way for novel energy storage technologies to participate in electricity markets as the qualifying facilities, thereby expanding opportunities for energy storage development. However, the existing policy, legal, and regulatory regime, including these much-welcomed newcomers, fails to recognize and support the entire spectrum of benefits that some forms of energy storage create. In this paper, we focus on Pumped Underground Storage Hydro (PUSH), a variant of pumped hydro storage (PHS), which currently provides over 90% of the world's energy storage capacity. PUSH operates with the same principle as PHS; however, it is an entirely underground variant of PHS. In addition to becoming competitive in the wholesale electricity market, PUSH facilities can be developed as community infrastructure in the postindustrial landscape, particularly in abandoned underground mines. Given federal energy law and policy development, this paper identifies how communities with abandoned mines, technically feasible for PUSH facilities and operating as municipal-owned utilities or cooperatives, can participate and take advantage of federal legislation. We further look into the implications through the lens of technical, economic, and social aspects of energy justice. We consider energy justice as a conceptual framework that seeks to explain the occurrence of injustice within energy system decisions and outcomes and how policymakers can respond to these injustices. We use it as a conceptual tool for understanding policy formulation and detailing the energy system's missing ethical and justice dimension. We argue that as a technically mature technology, PUSH facilities can act as a potential means to speed up the energy transition in the United States. The federal and state law along with utility market structures are vital in shaping the potential opportunities and barriers for energy storage facilities like PUSH. We show that although it supports PUSH development, there are gaps in the current market structure, specifically in the regulatory framework, when seen through the lens of justice and valuation of just energy services. These gaps limit the realization of utility-scale energy storage technology's potential to fully contribute to a decarbonized energy system that is more resilient and more just than the incumbent system.
Maturation Age of 55 Boys in the Little League World Series, 1957

Abstract The X-ray films of the hands of 55 boys in the Little League World Series, 1957, were assessed for maturation (skeletal) age according to Todd's 1937 standards. There were four boys of chronological age 11:0–11:9, 42 of age 12:0–12:11, 9 of age 13:0–13:11. It was found that 16 boys (29%) were retarded, or maturation age less than chronological age; 39 boys (71%) were advanced, or maturation age more than chronological age. With correction of maturation age within ± one year of chronological age, the significant figures are five retarded, 25 advanced, for a total of 30. Of these 17 percent are retarded, 83 percent advanced. It is concluded that Little League ball players of championship caliber are, in general, biologically advanced. Such an advancement is deemed a positive factor in young boys indulging in competitive sports.
Fair pricing using deflators and decrement copulas: the unit linked endowment approach

The Black-Scholes deflator and bivariate decrement copulas for the joint modeling of the time of death and time of withdrawal are used to determine the fair price of unit-linked endowment insurance contracts without or with a rising-floor guarantee. The fair fee income rate charged to the unit-linked fund is defined such that the present value of the fee income covers exactly the present value of the product guarantees and the expenses. In particular, a complete analytical treatment of the unit-linked endowment insurance without guarantee is presented.
Canine pancreatic ribosomes. II. The protein moiety.

Abstract The protein moiety of purified dog pancreatic ribosomes has been examined by starch gel electrophoresis in formate buffers, pH 3, containing 6 m urea. Densitometric tracings of the complex but reproducible electrophoretograms disclosed a minimum of 21 cationic components. Identical patterns were obtained with protein prepared by alternative extraction procedures, and these were not significantly altered by preparation of the ribosomes from a single dog pancreas or by the inclusion of puromycin during isolation of the ribosomes. Treatment of the protein from canine pancreatic ribosomes with dithiothreitol in urea resulted in very minor changes in electrophoretic properties, the suggestion being that most of the half-cystine residues of the protein are already in the reduced state. Protein from microsomal and postmicrosomal canine pancreatic ribosomes presented similar but not identical patterns. Electrophoretograms of protein moieties of purified ribosomes from dog and rabbit pancreas were compared. Most components were common to both species, but a few were characteristic of one species only. The species-specific bands are reproducible and independent of the method of preparation of the protein. Of the protein present in the 80 S monoribosome of dog pancreas, three components are localized exclusively or predominately in the large subunit, and five exclusively or predominately in the small subunit. One disappears upon dissociation and the remainder appear to be common to both subunits. Of the dog-specific bands, one appears only in the small subunit, one appears only in the large subunit, and one is present in both subunits.
An Evaluation of TTI and ASA in SID Side Impact Sled Tests

Thirty-seven SID side impact sled tests were performed using a rigid wall and a padded wall with fourteen different padding configurations. The Thoracic Trauma Index (TTI) and Average Spine Acceleration (ASA) were measured in each test. TTI and ASA were evaluated in terms of their ability to predict injury in identical cadaver tests and in terms of their ability to predict the harm or benefit of padding of different crush strengths. SID ASA predicted the injury seen in WSU-CDC cadaver tests better than SID TTI. SID ASA predicted that padding of greater than 20 psi crush strength is harmful (ASA gt; 40 g's). SID TTI predicted that padding of greater than 20 psi crush strength is beneficial (TTI less than 85 g's). SID TTI predicts the benefit of lower impact velocity. However, SID ASA appears more useful in assessing the harm or benefit of door padding or air bags. Language: en
Comparison of the Chemical Biology of NO and HNO: An Inorganic Perspective

KATRINA M. MIRANDA Department of Chemistry, University of Arizona, Tucson, AZ LISA RIDNOUR, MICHAEL ESPREY, DEBORAH CITRIN, DOUGLAS THOMAS, DANIELE MANCARDI, SONIA DONZELLI, and DAVID A. WINK Tumor Biology Section, Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD TATSUO KATORI, CARLO G. TOCCHETTI, MARCELLA FERLITO, and NAZARENO PAOLOCCI Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD JON M. FUKUTO Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA
Intelligent tutoring systems with conversational dialogue

Many of the intelligent tutoring systems that have been developed during the last 20 years have proven to be quite successful, particularly in the domains of mathematics, science, and technology. They produce significant learning gains beyond classroom environments. They are capable of engaging most students' attention and interest for hours. We have been working on a new generation of intelligent tutoring systems that hold mixed-initiative conversational dialogues with the learner. The tutoring systems present challenging problems and questions to the learner, the learner types in answers in English, and there is a lengthy multiturn dialogue as complete solutions or answers evolve. This article presents the tutoring systems that we have been developing. AutoTutor is a conversational agent, with a talking head, that helps college students learn about computer literacy. andes, atlas, and why2 help adults learn about physics. Instead of being mere information-delivery systems, our systems help students actively construct knowledge through conversations.
Utilizing a Social Ethic Toward the Environment in Assessing Genetically Engineered Insect-Resistance in Trees

Social policies are used to regulate how members of a society interact and share resources. If we expand our sense of community to include the ecosystem of which we are a part, we begin to develop an ethical obligation to this broader community. This ethic recognizes that the environment has intrinsic value, and each of us, as members of society, are ethically bound to preserve its sustainability. In assessing the environmental risks of new agricultural methods and technologies, society should not freely trade economic gains for ecological damage, but rather seek practices that are compatible with ecosystem health. This approach is used to evaluate the environmental risks associated with genetically engineered insect-resistant trees. The use of insect-resistant trees is a biologically based pest control strategy that has several advantages over pesticide use. However, the use of genetically engineered trees presents particular ecological concerns because the trees are long lived and often are not highly domesticated. The main environmental concerns reviewed include: (1) adaptation of pests to the trees, leading to a non-sustainable agricultural practice, (2) transgenic trees producing environmental toxins, (3) insect resistance enhancing the invasiveness of the tree, causing it to become weedy or invade wild habitats, and (4) transfer of the transgene to wild or feral relatives of the tree, possibly increasing the invasiveness of weeds or wild plants. Some methods are available to offset these risks; however, the environmental risks associated with this technology have been poorly researched and need to be more clearly identified so that when we evaluate the risks, it is based on the best information obtainable. To fulfil an ethical obligation to the environment, public policies and government regulations are needed to preserve the sustainability of both the environment and the future of our production systems. A better understanding of both the ecological issues and of genetic engineering in general are needed on the part of citizens and policy makers alike to ensure that sound environmental decisions are made. Otherwise, the environmental benefits of this technology, mainly decreasing the use of more toxic pesticides in tree crops and forests, will either be lost or traded for other environmental hazards.
Esophageal Spasm Associated with Apnea and Bradycardia in an Infant

A newborn infant was found to have diffuse esophageal spasm in association with apnea and bradycardia. This association has not been physiologically documented before. The infant9s condition improved after the administration of glycopyrrolate, an anticholinergic agent. It is speculated that the association of esophageal spasm and bradycardia may be mediated by the vagus.
Neurologic Complications of Osler-Weber-Rendu Syndrome: A Case Report and Literature Review (P3.058)

OBJECTIVE: Preventing the neurologic complications of Osler-Weber-Rendu Syndrome (OWRS), also known as hereditary hemorrhagic telangiectasia, by early diagnosis and appropriate treatment. BACKGROUND: OWRS is a rare genetic disorder characterized by telangiectasias and excessive bleeding. Brain abscess and ischemic stroke are rare but potentially serious complications, caused by paradoxical embolism from pulmonary arteriovenous malformations (AVMs). DESIGN/METHODS: We describe case of a 56 year old woman with past medical history of OWRS who presented to emergency department for suspected stroke. MRI revealed a brain abscess which was treated with antibiotic therapy. A pulmonary angiogram revealed recanalized arteriovenous malformation in the left lobe of lung which was embolised 15 years ago. RESULTS: Endovascular embolization was done to avoid future neurologic complications and routine follow-up was indicated to prevent recanalization of embolised AVM and other complications of the procedure. CONCLUSIONS: Brain abscess or ischemic stroke must be expected in patients with history of OWRS who present with neurologic manifestations. Family members of such patients should be screened for OWRS with appropriate genetic testing. All the patients with OWRS, whether symptomatic or not, should be screened for pulmonary AVMs. If found, pulmonary AVM’s should be treated to prevent paradoxical embolism which can result in brain abscess or ischemic stroke, both of which can be potentially fatal. Endovascular embolization is the treatment of choice for pulmonary AVMS and a long term follow-up is recommended after the procedure to prevent any complications. Those patients treated for pulmonary AVMs, likely should be screened for recanalization with a pulmonary angiogram at routine intervals, suggested to be every 10 years. Our case illustrates that CT angiogram can be insufficient for this task. Study Supported by: Self Disclosure: Dr. Farooq has nothing to disclose. Dr. Mowla has nothing to disclose. Dr. AbdelRazek has nothing to disclose. Dr. Iqbal has nothing to disclose. Dr. Sawyer has nothing to disclose.
Goal-Directed Value Profiling

Compilers can exploit knowledge that a variable has a fixed known value at a program point for optimizations such as code specialization and constant folding. Recent work has shown that it is possible to take advantage of such optimizations, and thereby obtain significant performance improvements, even if a variable cannot be statically guaranteed to have a fixed constant value. To do this profitably, however, it is necessary to take into account information about the runtime distribution of values taken on by variables. This information can be obtained though value profiling. Unfortunately, existing approaches to value profiling incur high overheads, primarily because profiling is carried out without consideration for the way in which the resulting information will be used. In this paper, we describe an approach to reduce the cost of value profiling by making the value profiler aware of the utility of the value profiles being gathered. This allows our profiler to avoid wasting resources where the profile can be guaranteed to not be useful for optimization. This results in significant reductions in both the time and space requirements for value profiling. Our approach, implemented in the context of the alto link-time optimizer, is an order of magnitude faster, and uses about 5% of the space, of a straightforward implementation.
How Transformative is the European Project

Joseph Weiler’s seminal Yale Law Journal essay of 1991, "The Transformation of Europe," poses two bold, persistent questions. Can we view European integration as a transformative project? And if so, has it achieved the transformation it set out to achieve? The questions are deceptive in their simplicity, not least because transformation is a notoriously inconstant metric. This paper begins by reviewing rival understandings of what a "transformation" of Europe might entail. It then argues that although the European project originally sought a new model of political obligation based on a reciprocal, deliberate, and rational commitment on the part of nation-states and their citizens to abide by shared political principles; it has fallen remarkably short of that ideal. The gradual fading of this normatively rich vision has left us with a market-inflected supra-nationalism that oscillates between crude national sovereignty and an equally crude form of instrumentally rational integration.
A Traveling Michelson Interferometer with Phase-Locked Fringe Interpolation

The advent of single-mode cw dye lasers and their application to Doppler-free spectroscopy makes essential the capability of rapidly measuring the dye laser’s wavelength with sub-Doppler absolute accuracy. Our wavelength measuring apparatus [1] is basically an automatic-scanning Michelson interferometer utilizing corner-cube retroreflectors, with phase multiplication for extending the resolution. The interferometer measures an unknown wavelength in terms of a reference laser wavelength. Motion of the carriage holding the corner-cubes lengthens one arm and shortens the other arm of this interferometer. For a given distance traveled by the carriage, a different number of fringes will be counted for the unknown laser and the reference laser (since their wavelengths are different). Naturally, a higher resolution level for the measured wavelength will require a longer travel, and consequently, a longer measuring time. Our resolution-extension concept, however, enables us to obtain wavelength information of a given resolution level in 100-fold less time than is required with direct fringe counting.
Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells

Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells. Polyethylene glycol-SOD addition reversed the GSE-mediated apoptosis without restoring complex III activity. Along with redox changes, GSE inhibited the extracellular acidification rate (representing glycolysis) and oxygen consumption rate (indicating oxidative phosphorylation) leading to metabolic stress in HNSCC cells. Molecular studies revealed that GSE activated AMP-activated protein kinase (AMPK), and suppressed Akt/mTOR/4E-BP1/S6K signaling in both Detroit 562 and FaDu cells. Interestingly, GSE increased the autophagic load specifically in FaDu cells, and autophagy inhibition significantly augmented the apoptosis in these cells. Consistent with in vitro results, in vivo analyses also showed that GSE feeding in nude mice activated AMPK and induced-autophagy in FaDu xenograft tumor tissues. Overall, these findings are innovative as we for the first time showed that GSE targets ETC complex III and induces oxidative and metabolic stress, thereby, causing autophagy and apoptotic death in HNSCC cells.
Epidermal Growth Factor Receptor (EGFR)-targeted Immunoliposomes Mediate Specific and Efficient Drug Delivery to EGFR- and EGFRvIII-overexpressing Tumor Cells

We hypothesized that immunoliposomes (ILs) that target epidermal growth factor receptor (EGFR) and/or its truncated variant EGFRvIII can be constructed to provide efficient intracellular drug delivery in tumor cells overexpressing these receptors. Monoclonal antibody fragments included Fab' fragments derived from C225, which binds both EGFR and EGFRvIII, or novel anti-EGFR scFv C10, which binds EGFR only. Monoclonal antibody fragments were covalently linked to liposomes containing various reporters or drugs. ILs were evaluated for specific binding, internalization, and cytotoxicity in EGFR/EGFRvIII-overexpressing cell lines in vitro. Flow cytometry and fluorescence microscopy showed that EGFR-targeted ILs, but not nontargeted liposomes or irrelevant ILs, were efficiently bound and internalized by EGFR-overexpressing cells, including glioma cells (U-87), carcinoma cells (A-431 and MDA-MB-468), and EGFRvIII stable transfectants (NR-6M). Furthermore, EGFR-targeted ILs did not bind to non-EGFR-overexpressing cells (MCF-7 and parental NR-6). ILs showed 3 orders of magnitude greater accumulation in NR-6-EGFRvIII stable transfectants versus parental NR-6 cells. Quantitative internalization studies indicated binding of EGFR-targeted ILs to target cells within 5 min, followed by intracellular accumulation beginning at 15 min; total uptake reached approximately 13,000 ILs/cell. ILs were used to deliver cytotoxic drugs doxorubicin, vinorelbine, or methotrexate to EGFR/EGFRvIII-overexpressing target cells in vitro. In each case, the IL agent was significantly more cytotoxic than the corresponding nontargeted liposomal drug in target cells, whereas it was equivalent in cells lacking EGFR/EGFRvIII overexpression. We conclude that EGFR-targeted ILs provide efficient and targeted delivery of anticancer drugs in cells overexpressing EGFR or EGFRvIII.
Relative Sensitivity of Selected Distributed Lag Estimators to Measurement and Specification Error

The notion that one economic variable has an impact on another over several time periods is not uncommon to economic thought. Irving Fisher was the first to introduce empirically the notion of distributed lags using different shapes of probability curves. Alt continued the work, but made no a priori assumptions about the distribution of the lag as Fisher had done. Koyck and Nerlove returned to and extended the work of Fisher assuming a priori a monotonically declining distribution. More recently Jorgenson, Almon, and Johnson have developed estimators which, like those of Alt, assume only a continuous lag function of unspecified shape. There is evidence, however, that the Jorgenson and Johnson techniques are extremely sensitive to errors of measurement and specification because in applied work, reasonable estimates of lag distributions occur infrequently.
Chelae regeneration in European alien crayfish Orconectes limosus (Rafinesque 1817)

Key-words: non-indigenous, crayfish, invasive, chelae, regeneration, growth Crayfish chelae have important functions, including prey capture and manipulation, reproduction, defense against predators, and inter- and intraspecific interactions. Consequently a loss of chelae often occurs. Adult specimens of invasive spiny-cheek crayfish (Orconectes limosus )w ere reared from February to November 2008 to observe the ability to regenerate lost chelae. Percent molt increments (PMI) of postorbital carapace length (POCL), chela length (ChL) and width (ChW) were compared between crayfish with and without chelae. Regenerated chelae were found to grow faster (ChL, ChW) than initial chelae and POCL. This trend occurs in both reproductive and non-reproductive O. limosus males and females. Values of 55.6 ± 0.06% for ChL and 50.0 ± 0.06% for ChW, compared to the initial chelae, were obtained in regenerated chelae of adult O. limosus after one molt. After two molts regenerated chelae reached 67.6 ± 0.07% ChL and 69.7 ± 0.08% ChW of values for initial chelae. Growth rate of regenerated chelae decreased with an increase in chelae dimensions. Regenerated chelae were found to be more narrow (significantly lower ChW/ChL ratio) than initial chelae. Regenerating of chelae did not have any influence on POCL growth. This study presents evidence that the invasive O. limosus possesses the ability of rapid substitution of lost chelae.
Long-Term Annual and Seasonal Patterns of Acidic Deposition and Stream Water Quality in a Great Smoky Mountains High-Elevation Watershed

The recovery potential of stream acidification from years of acidic deposition is dependent on biogeochemical processes and varies among different acid-sensitive regions. Studies that investigate long-term trends and seasonal variability of stream chemistry in the context of atmospheric deposition and watershed setting provide crucial assessments on governing biogeochemical processes. In this study, water chemistries were investigated in Noland Divide watershed (NDW), a high-elevation watershed in the Great Smoky Mountains National Park (GRSM) of the southern Appalachian region. Monitoring data from 1991 to 2007 for deposition and stream water chemistries were statistically analyzed for long-term trends and seasonal patterns by using Seasonal Kendall Tau tests. Precipitation declined over this study period, where throughfall (TF) declined significantly by 5.76 cm year−1. Precipitation patterns play a key role in the fate and transport of acid pollutants. On a monthly volume-weighted basis, pH of TF and wet deposition, and stream water did not significantly change over time remaining around 4.3, 4.7, and 5.8, respectively. Per NDW area, TF SO42- flux declined 356.16 eq year−1 and SO42- concentrations did not change significantly over time. Stream SO42- remained about 30 μeq L−1 exhibiting no long-term trends or seasonal patterns. SO42- retention was generally greater during drier months. TF monthly volume-weighted NH4+ and NO3- concentrations significantly increased by 0.80 μeq L−1 year−1 and 1.24 μeq L−1 year−1, respectively. TF NH4+ fluxes increased by 95.76 eq year−1. Most of NH4+ was retained in the watershed, and NO3- retention was much lower than NH4+. Stream monthly volume-weighted NO3- concentrations and fluxes significantly declined by 0.56 μeq L−1 year−1 and 139.56 eq year−1, respectively. Overall, in NDW, inorganic nitrogen was exported before 1999 and retained since then, presumably from forest regrowth after Frazer fir die-off in the 1970s from balsam wooly adelgid infestation. Stream export of NO3- was greater during winter than summer months. During the period from 1999 to 2007, stream base cations did not exhibit significant changes, apparently regulated by soil supply. Statistical models predicting stream pH, ANC, SO42-, and NO3- concentrations were largely correlated with stream discharge and number of dry days between precipitation events and SO42- deposition. Dependent on precipitation, governing biogeochemical processes in NDW appear to be SO42- adsorption, nitrification, and NO3- forest uptake. This study provided essential information to aid the GRSM management for developing predictive models of the future water quality and potential impacts from climate change.