cssi/SciSciGPT-SciSciNet huggingface dataset:
The Growth of Liver Parenchymal Nuclei and Its Endocrine Regulation

Publisher Summary One of the significant characteristics of hepatic parenchyma is the presence of polyploid nuclei and of binucleated and multinucleated cells. These are encountered in varying numbers in the livers of many adult vertebrates, especially mammals, but they are relatively rare, or even absent in fetal and newborn individuals. Hormones exert an influence on several phenomena which are closely related to nuclear growth in terms of DNA synthesis. They regulate the relative numbers of polyploid and binucleated cells, as well as mitotic index and mitotic diurnal periodicity. Values intermediate among diploid, tetraploid, and octoploid DNA contents can be found in increased numbers where cell proliferation and DNA synthesis are more active than in normal adults, for example, in embryonic and newborn animals, in adult livers stimulated to repair by thioacetamide injury or dimethylnitrosamine, or by partial hepatectomy. The relationship of protein content to nuclear size is also investigated. The uptake, synthesis, and release of materials by the nucleus are influenced by environmental conditions, and changes of nuclear size related to altered protein content in response to physiological stimuli, without change in the amount of DNA, is observed in tissues other than liver, for example in rat uterine glands and thyroid.
Robust Koopman Operator-based Kalman Filter for Power Systems Dynamic State Estimation

This paper develops a robust generalized maximum-likelihood Koopman operator-based Kalman filter (GM-KKF) to estimate the rotor angle of synchronous generators. The approach is data-driven and model independent. The design phase is carried out offline and requires estimates of the synchronous generators’ rotor angle and active and reactive power; in real-time operation, only measurements of active and reactive power at the terminal of the synchronous generators are assumed. We first investigate the probability distribution of the dynamic states by means of Q-Q plots and verify that the states of the GM-KKF approximately follow a Student’s t-distribution with 20 degrees of freedom when the initial state vector is normally distributed. Under this assumption, our filter presents high statistical efficiency. Then, we carry out numerical simulations on the IEEE 39-bus test system. They reveal that the GM-KKF has a faster convergence rate than the non-robust Koopman operator-based Kalman filter. They also show that the computing time of the GM-KKF is roughly reduced by one-third as compared to the one taken by our previously developed robust GM-extended Kalman filter.
Heavy rainfall, famine, and cultural response in the West African Sahel: the ‘Muda’ of 1953–54

One of the worst Sahel famines of the twentieth century was initiated by heavy rainfall in 1953. Famine-impelled household migration and elevated rates of morbidity and mortality were widespread. A famine triggered by heavy rains would present a serious challenge to contemporary early warning systems that rely on analysis of food prices and satellite-derived measures of vegetation. In the absense of frequent and extensive field reporting, an effective early warning system would require collection and analysis of daily rainfall data and the development of accurate Sahel climate-crop yield models.
Did They Hurt Growth? A Synthetic Control Estimate of the Impact of 'Bachelet's Reforms'

This paper uses the synthetic control method to estimate the short-term impact on GDP of the reforms implemented between 2014 and 2017 in Chile by the government of President Michelle Bachelet. I find a cumulative fall by the end of 2017 of 13% relative to the synthetic counterfactual. This result is robust to the use of a donor pool that includes economies for which primary commodities are relevant, as well as one that only includes OECD countries.
Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study.

Question Is broad-spectrum antibiotic use associated with poor outcomes in community-onset pneumonia after adjusting for confounders? Methods We performed a retrospective, observational cohort study of 1995 adults with pneumonia admitted from four US hospital emergency departments. We used multivariable regressions to investigate the effect of broad-spectrum antibiotics on 30-day mortality, length of stay, cost and Clostridioides difficile infection (CDI). To address indication bias, we developed a propensity score using multilevel (individual provider) generalised linear mixed models to perform inverse-probability of treatment weighting (IPTW) to estimate the average treatment effect in the treated. We also manually reviewed a sample of mortality cases for antibiotic-associated adverse events. Results 39.7% of patients received broad-spectrum antibiotics, but drug-resistant pathogens were recovered in only 3%. Broad-spectrum antibiotics were associated with increased mortality in both the unweighted multivariable model (OR 3.8, 95% CI 2.5–5.9; p Conclusion Broad-spectrum antibiotics appear to be associated with increased mortality and other poor outcomes in community-onset pneumonia.
Flexible, Free Software for Multilevel Multiple Imputation: A Review of Blimp and jomo:

Multiple imputation is a popular method for addressing data that are presumed to be missing at random. To obtain accurate results, one’s imputation model must be congenial to (appropriate for) one’...
What Makes It Sound ’80s?: The Yamaha DX7 Electric Piano Sound

Popular music of the 1980s is remembered today as having a “sound” that is somehow unified and generalizable. The ’80s sound is tied to the electric piano preset of the Yamaha DX7 synthesizer. Not only was this preset (E. PIANO 1) astonishingly prevalent—heard in up to 61% of #1 hits on the pop, country, and RB and two, cultural positioning in a greater lineage of popular music history. This article analyzes the timbre of E. PIANO 1 by combining ethnographic study of musician language with visual analysis of spectrograms, a novel combination of techniques that links acoustic specificity with social context. The web of connections created by the use and re-use of DX7 presets like E. PIANO 1, among hundreds or maybe thousands of different tracks and across genres, is something that allows modern listeners to abstract a unified notion of the “’80s sound” from a diverse and eclectic repertoire of songs produced in the 1980s.
Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): An Update

Based on evidence accumulated over the past three decades showing that noninvasive encapsulated follicular variant of papillary thyroid carcinoma has an indolent clinical behavior and a RAS-like molecular profile similar to follicular adenoma, the Endocrine Pathology Society working group in 2016 proposed to rename this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" in order to eliminate the term "carcinoma" from the diagnosis. It is a major evidence-based attempt initiated by an international group of endocrine pathologists to tackle the epidemic of thyroid cancer overdiagnosis and overtreatment. However, its creation and continuous existence are not without controversies. NIFTP has sparked a wave of follow up studies aiming to decipher the exact nature of this new entity. In this review, we summarize the rationale, diagnostic criteria, controversies and subsequent changes to the NIFTP concept, and their impact on patient care and pathology practice.
Online updating method to correct for measurement error in big data streams

Abstract When huge amounts of data arrive in streams, online updating is an important method to alleviate both computational and data storage issues. The scope of previous research for online updating is extended in the context of the classical linear measurement error model. In the case where some covariates are unknowingly measured with error at the beginning of the stream, but then are measured without error after a particular point along the data stream, the updated estimators ignoring the measurement error are biased for the true parameters. Once the covariates measured without error are first observed, a method to correct the bias of the estimators, as well as to correct the biases in their variance estimator, is proposed; after correction, the traditional online updating method can then proceed as usual. Further, asymptotic distributions for the corrected and updated estimators are established. Simulation studies and a real data analysis with an airline on-time dataset are provided to illustrate the performance of the proposed method.
2.17 – Optical Microscopy

Optical microscopy, although a long-established characterization technique, has seen a large number of changes in recent years. These may involve higher resolution, higher speed of data acquisition, more quantitative results, or more sensitive detection. Most of these advances have been driven by biological applications but are relevant to polymer microscopy. This chapter gives some background of standard imaging modes and describes advances in polarized light microscopy, three-dimensional microscopy, and digital microscopy. Scanning optical microscopes and ‘super-resolution’ modes are covered in Chapters 2.18–2.20 2.18 2.19 2.20.
Another Unorthodox Introduction to QCD and now Machine Learning

These are lecture notes presented at the online 2020 Hadron Collider Physics Summer School hosted by Fermilab. These are an extension of lectures presented at the 2017 and 2018 CTEQ summer schools in arXiv:1709.06195 and still introduces perturbative QCD and its application to jet substructure from a bottom-up perspective based on the approximation of QCD as a weakly-coupled, conformal field theory. With machine learning becoming an increasingly important tool of particle physics, I discuss its utility exclusively from the biased view for increasing human knowledge. A simple argument that the likelihood for quark versus gluon discrimination is infrared and collinear safe is presented as an example of this approach. End-of-lecture exercises are also provided.
Quantifying Good Seamanship For Autonomous Surface Vessel Performance Evaluation

The current state-of-the-art for testing and evaluation of autonomous surface vehicle (ASV) decision-making is currently limited to one-versus-one vessel interactions by determining compliance with the International Regulations for Prevention of Collisions at Sea, referred to as COLREGS. Strict measurement of COLREGS compliance, however, loses value in multi-vessel encounters, as there can be conflicting rules which make determining compliance extremely subjective. This work proposes several performance metrics to evaluate ASV decision-making based on the concept of "good seamanship," a practice which generalizes to multi-vessel encounters. Methodology for quantifying good seamanship is presented based on the criteria of reducing the overall collision risk of the situation and taking early, appropriate actions. Case study simulation results are presented to showcase the seamanship performance criteria against different ASV planning strategies.
Challenging the politics of education: Intertwining dialogic pedagogy with a research-based practicum for first-year pre-service teachers

The public education system in the United States has long been under assault from neoliberal educational reforms. Those reforms have been characterized by anti-democratic and homogenizing assessment methods and systems that reinforce the banking model of education. In this model, students learn to passively and uncritically consume the knowledge transmitted to them in school. In order to counteract the banking model, this research urged first-year, pre-service teachers (PSTs) in an Introduction with Internship in Bilingual/ESL Education college coursework to engage in a dialogic problem-posing pedagogy grounded in a Freirian perspective. PSTs conducted a mini research-based practicum (RBP) that was six weeks long and required a total of 24-hour field observations across local public elementary schools. The RBP framework consisted of a research question, a mini literature review, practicum observations, findings, a group-written report, and a group presentation. In this study, we analyzed the RBP process and data sources that responded to our guiding question: What counts as good teaching according to PSTs? The major findings included: (a) good teaching means relationship building, (b) good teaching starts with understanding the multiple roles of the teacher, and (c) good teaching is inclusive. We discussed the transformative moves that PSTs went through while engaging in a dialogic problem-posing pedagogy. Teacher-educators (TEs) can benefit from this study, as the viability of the transformative effects of a dialogic problem-posing pedagogy, along with its challenges and coping methods, were discussed.
Strain-driven surface reconstruction and cation segregation in layered Li(Ni1−x−yMnxCoy)O2 (NMC) cathode materials

The composition, structure and phase transformations occurring on cathode surfaces greatly affect the performance of Li-ion batteries. Li-Ion diffusion and surface–electrolyte interaction are two major phenomena that impact the capacity and cell impedance. The effects of surface reconstruction (SR) of cathode materials on the performance of Li-ion batteries are of current interest. However, the origin and evolution of the SR are still not well understood. In this work, density functional theory (DFT) calculations are used to investigate the processes taking place during surface segregation and reconstruction. Facet dependent segregation was found in Li(Ni1−x−yMnxCoy)O2 (NMC) cathodes. Specifically, Co tends to segregate to the (104) surface of the primary particles within the transition metal layer, while Ni ions tend to segregate to the (012) surface in the Li layer, forming a SR. Experimental evidence shows the SR to be epitaxial with the bulk of the as-synthesized material, and the new SR phase is pinned to the NMC unit cell leading to a strained SR. Here, we show that strain can stabilize a spinel structure of the SR layers. Understanding the effects of surface strain opens a new avenue for the design of cathode materials with enhanced surface properties.
Compensation and Taxes: Evidence from Relative Performance Evaluation

Relative performance evaluation (RPE) is a common practice in compensation contracting, essentially conditioning management compensation on the achievement of certain performance goals relative to a benchmark. In this paper, we examine the incentive effects of RPE usage on tax outcomes. We predict and find that low-tax peers in RPE contracts influence focal firm tax outcomes. Specifically, we find that a greater proportion of low-tax RPE peers embedded in RPE compensation contracts is associated with lower book and cash effective tax rates, and we find evidence that this effect is not confined to RPE peers within the same industry. Moreover, we also find that the tax outcomes incentivized through low-tax RPE peers occurs through RPE grants conditional on achieving after-tax earnings metrics. Overall, our results reveal that RPE provides a meaningful influence on corporate tax outcomes.
Transient Competitive Inhibition Bypasses the Binding Site Barrier to Improve Tumor Penetration of Trastuzumab and Enhance T-DM1 Efficacy.

Poor penetration of monoclonal antibodies (mAb) in solid tumors is explained in part by the binding site barrier hypothesis. Following extravasation, mAbs rapidly bind cellular antigens, leading to the observation that, at sub-saturating doses, therapeutic antibody in solid tumors localizes around tumor vasculature. Here we report a unique strategy to overcome the binding site barrier through transient competitive inhibition of antibody-antigen binding. The anti-trastuzumab single domain antibody 1HE was identified through in vitro binding assays as a model inhibitor. Co-administration of 1HE did not alter the plasma pharmacokinetics of trastuzumab or ado-trastuzumab emtansine (T-DM1) in vivo. Administration of 1HE alone was rapidly eliminated with a terminal plasma half-life of 1.2 hours, while co-administrations of 1HE with trastuzumab had a terminal half-life of 56 hours. In mice harboring SKOV3 xenografts, co-administration of 1HE with trastuzumab led to significant increases in both penetration of trastuzumab from vasculature and the percent of tumor area that stained positive for trastuzumab. 1HE co-administered with a single dose of T-DM1 to NCI-N87 xenograft bearing mice significantly enhanced T-DM1 efficacy, increasing median survival. These results support the hypothesis that transient competitive inhibition can improve therapeutic antibody distribution in solid tumors and enhance antibody efficacy.
Drugs of Abuse-Opioids, Sedatives, Hypnotics.

Over the last 2 decades, prescription and nonprescription substance use has significantly increased. In this article, 3 particular drug classes-opioids, sedatives, and hypnotics-are discussed. For each class, a brief history of the agent, a description of relevant pharmacology, the clinical presentation of overdose, the management of specific drug overdoses, and a summary of salient points are presented. The intent is to provide a clinically relevant and comprehensive approach to understanding these potential substance exposures in order to provide a framework for management of opioid, sedative, and hypnotic overdoses.
The MD Anderson Cancer Hospital That R. Lee Clark Built.

The MD Anderson Hospital for Cancer Research (as it was named in 1946) incorporated pioneering changes that set new standards in hospital design, construction, and function. It is remarkable that surgeon R. Lee Clark, the new Director of the MD Anderson Hospital, and with no previous experience in hospital construction, personally led the design and supervision of a world class medical care and research facility. This is the untold story of his leadership and his diligence visiting hospitals and cancer facilities in America and Europe, his clever hiring, his supervision of the architectural firms (through 23 versions of architectural plans), his adaptability to the market when building costs were skyrocketing, and his extraordinary ability in raising enormous funds from private, state, and federal sources. He was such a creative genius in his inaugural building project that the new MD Anderson “cancer station” was described by national magazines as totally unique in its design that set new standards in cancer care delivery. With his typical determination, enthusiasm, and creative approach to problem-solving, Clark embarked on this building project in 1946 with a budget of $1,750,000, expecting to complete this project in 2 to 3 years. In fact, the entire project took 8 years and cost five times more than the original estimate, at almost $9,000,000! The process took 2 years for Dr. Clark to visit more than 30 cancer facilities and many academic hospitals in America and in Europe, 2 years of architectural planning, and 4 years of construction. When MD Anderson opened its doors in 1954, it was described by national magazines as “one of the most modern hospitals in the nation.”
Effect of SEC enforcement actions on forced turnover of executives: Evidence associated with SOX provisions

Abstract This study examines the impact of SEC enforcement actions on the turnovers of culpable CEOs and CFOs named in the enforcement actions, following their violations of the SOX provisions. We compare the impact on CEO turnover with that on CFO turnover. The impact in the pre-SOX period and that in the post-SOX period are also compared. Findings of this study provide evidence that the SEC enforcement actions are associated with the probabilities of turnovers of CEOs and CFOs named in the SEC enforcement actions for violations of SOX 303 and SOX 305. Specifically, CEOs sanctioned by the SEC are likely to lose their positions when they violate SOX 305. In contrast, CFOs sanctioned by the SEC for violating SOX 303 are likely to be forced to resign. When CFOs are named as mastermind by the SEC, they are likely to lose jobs. However, when both CEO and CFO are named as masterminds in fraudulent financial reporting, CFOs are less likely to be removed. In addition, CEOs and CFOs are likely to lose their jobs when firms face bankruptcy and restate earnings and when they face criminal charges, especially in the post-SOX period.
Who Are These Professor Pundits

This chapter brings academics into the consideration by discussing results from a national survey of professors asking about their relative frequency and type of media appearances. The results show that most academics are relatively infrequent media contributors, but that, over time, many garner a substantial degree of experience doing this work. At the same time, academics find a general sense of satisfaction in their media appearances, even if certain aspects of the work raise stress levels (especially in television interviews).
Professional development needs of novice alternatively certified teachers in Florida: teachers’ perspectives

Alternative teacher certification routes in the United States gained recognition in response to the teacher shortage since the 1980s. However, the unique challenges these teachers face result in co...
The 2018 Applications for the Delzie Demaree Travel Award

The Delzie Demaree Travel Award was established in 1988 honoring Delzie Demaree who attended 35 out of a possible 36 symposia before he died in 1987. Delzie Demaree was a frontier botanist, explorer, discoverer, and teacher. His teaching career as a botanist began in Arkansas at Hendrix College in 1922. He also taught botany at the University of Arkansas, Navajo Indian School, Yale School of Forestry, Arkansas A&M, and Arkansas State University at Jonesboro where he retired as professor emeritus in 1953. One of the things he enjoyed most as a botanist was assisting students with their field botany research.
Deregulation and the Lawyers' Cartel

At one time, the legal profession largely regulated itself. However, based on the economic notion that increased competition would benefit consumers, jurisdictions have deregulated their legal markets by easing rules relating to attorney advertising, fees, and, most recently, nonlawyer ownership of law firms. Yet, despite reformers’ high expectations, legal markets today resemble those of previous decades, and most legal services continue to be delivered by traditional law firms. How to account for this seeming inertia? We argue that the competition paradigm is theoretically flawed because it fails to fully account for market failures relating to asymmetric information, imperfect information, and negative externalities. In addition, the regulatory costs imposed on sophisticated consumers such as corporate purchasers of legal services differ radically from those imposed on ordinary consumers who use legal services infrequently. Merely increasing the number and types of legal services providers cannot make legal markets more efficient. We illustrate our theoretical account with evidence from the United Kingdom, Europe, and Asia. For legal markets to better serve the public, regulators must tailor solutions by segment. Regulators should seek to minimize negative externalities associated with the delivery of legal services to the corporate segment and confront information asymmetries that lead to the maldistribution of legal services in the consumer segment. Deregulation alone is insufficient and may in fact exacerbate existing market failures.
Low-temperature emergent neuromorphic networks with correlated oxide devices.

Author(s): Goteti, Uday; Zaluzhnyy, Ivan; Ramanathan, Shriram; Frano, Alex; Dynes, Robert | Abstract: Neuromorphic computing-which aims to mimic the collective and emergent behavior of the brains neurons, synapses, axons, and dendrites-offers an intriguing, potentially disruptive solution to societys ever-growing computational needs. Although much progress has been made in designing circuit elements that mimic the behavior of neurons and synapses, challenges remain in designing networks of elements that feature a collective response behavior. We present simulations of networks of circuits and devices based on superconducting and Mott-insulating oxides that display a multiplicity of emergent states that depend on the spatial configuration of the network. Our proposed network designs are based on experimentally known ways of tuning the properties of these oxides using light ions. We show how neuronal and synaptic behavior can be achieved with arrays of superconducting Josephson junction loops, all within the same device. We also show how a multiplicity of synaptic states could be achieved by designing arrays of devices based on hydrogenated rare earth nickelates. Together, our results demonstrate a research platform that utilizes the collective macroscopic properties of quantum materials to mimic the emergent behavior found in biological systems.
Accuracy-Privacy Trade-off in Deep Ensemble: A Membership Inference Perspective

Deep ensemble learning has been shown to improve accuracy by training multiple neural networks and fusing their outputs. Ensemble learning has also been used to defend against membership inference attacks that undermine privacy. In this paper, we empirically demonstrate a trade-off between these two goals, namely accuracy and privacy (in terms of membership inference attacks), in deep ensembles. Using a wide range of datasets and model architectures, we show that the effectiveness of membership inference attacks also increases when ensembling improves accuracy. To better understand this trade-off, we study the impact of various factors such as prediction confidence and agreement between models that constitute the ensemble. Finally, we evaluate defenses against membership inference attacks based on regularization and differential privacy. We show that while these defenses can mitigate the effectiveness of the membership inference attack, they simultaneously degrade ensemble accuracy. We illustrate similar trade-off in more advanced and state-of-the-art ensembling techniques, such as snapshot ensembles and diversified ensemble networks. The source code is available in supplementary materials.
Response of Human Vascular Cells to Viral Infection

Injury to blood vessel cells has been implicated in the development of a variety of vascular disorders including atherosclerosis,2,15 disseminated intravascular coagulation,9 and immune vasculitis.56 Endothelial cell (EC) injury can arise from a variety of causes including hemodynamic stress,64 mechanical trauma,65 hypercholesterolemia,57 infectious agents,16,49,54 oxygen33 and other chemical agents such as homocysteine.74 Renewed interest in the relationship between vascular injury due to viral infection and atherosclerosis stems from recent observations which demonstrated that virus particles, virus antigens, and virus DNA can be detected in vascular lesions of chickens11,49 and humans4,23,48,76 with atherosclerosis. Viruses may produce vascular injury by mechanisms other than direct invasion of endothelium. Antigen-antibody complexes involving hepatitis B surface antigen have been isolated from the sera of some patients with periarteritis nodosa.19 Tumor formation as a result of viral infection is another possible mechanisms by which viruses may induce vascular disease as is the case with cytomegalovirus and Kaposi’s sarcoma.22 At the time our laboratory began investigating the in vitro interaction between virus and EC,8,17,45 few such studies had been reported.1,20 Since the last review, Visser et al.72 reported enhanced thrombin generation and platelet binding on herpes simplex virus (HS V)-infected endothelium and Dunn and Spear80 demonstrated that cell surface heparan sulfate proteoglycan serves as the initial receptor for both HSV-1 and HSV-2 in HEp-2 cells. In this report I essentially summarize our published work as well as recently published work by other investigators.
Terahertz Spectroscopy : Principles and Applications

Preface Instrumentation and Methods Terahertz Time-Domain Spectroscopy with Photoconductive Antennas R. Alan Cheville Nonlinear Optical Techniques for Terahertz Pulse Generation and Detection-Optical Rectification and Electrooptic Sampling Ingrid Wilke and Suranjana Sengupta Time-Resolved Terahertz Spectroscopy and Terahertz Emission Spectroscopy Jason B. Baxter and Charles A. Schmuttenmaer Applications in Physics and Materials Science Time-Resolved Terahertz Studies of Carrier Dynamics in Semiconductors, Superconductors, and Strongly Correlated Electron Materials Robert A. Kaindl and Richard D. Averitt Time-Resolved Terahertz Studies of Conductivity Processes in Novel Electronic Materials Jie Shan and Susan L. Dexheimer Optical Response of Semiconductor Nanostructures in Terahertz Fields Generated by Electrostatic Free-Electron Lasers Sam Carter, John Cerne, and Mark S. Sherwin Applications in Chemistry and Biomedicine Terahertz Spectroscopy of Biomolecules Edwin J. Heilweil and David F. Plusquellic Pharmaceutical and Security Applications of Terahertz Spectroscopy J. Axel Zeitler, Thomas Rades, and Philip F. Taday Index
Fire and Light, Four Poets to the End and Beyond

Our poetry is poetry of the body, full of blood, blood for intimacy, but more often blood for death. In Sylvia Plath blood is the sign of death intimately ren dered. But if the early sixties were marked by poetry, like hers, of personal en gagements with despair and death, the last years of the decade were dominated by evocations of a more general human movement toward dark ends and changes in being. In 1967 four central poets?Robert Bly, Ted Hughes, James Dickey, and W. S. Merwin?published collections of poetry about cultural death and transformation which in very different ways reflected a wide sense of deep crisis and change inadequately described as "apocalyptic." These books, and the more recent work of these four poets, seem to form a dominant contemporary pattern not only because of intersecting visions but because of similar styles created to cope with these visions. The three Americans and Hughes, the most American of contemporary British poets, have developed variations of a deeply visceral surrealism. Each man writes highly individual poetry, and each individual style is in the process of change, usually toward greater bluntness and greater com plexity. But each poet has written lines that could be attributed to one or more of the others.
The good and bad sides of thiols as one-electron donors in free radical processes

Redox reactions of thiols play important roles in many biologic processes including signaling, enzymatic reactions and the defense against reactive oxygen species. These redox reactions proceed via one-electron or two-electron oxidation and reduction processes. Especially the one-electron redox reactions lead to free radical species such as thiyl radicals, and a potential role for thiyl radicals in signaling, the formation of S-nitroso-thiols, and higher oxidation products of thiols has been discussed. However, thiyl radicals are generally quite reactive towards many classes of biomolecules, including polyunsaturated fatty acids, carbohydrates, and proteins. This presentation will focus on deleterious reactions of thiyl radicals, particularly hydrogen transfer reactions within peptides and proteins, which can lead to the generation of a manifold of different products, including electrophiles, D-amino acids, cross-links and fragmentation products. Examples will be provided for glutathione (GSH), GAPDH, SERCA and a number of antibodies. These reactions proceed with some sequence specificity. Rate constants for these hydrogen transfer processes have been derived by NMR spectroscopy, mass spectrometry, and pulse radiolysis, indicating that they can compete against the reaction of thiyl radicals with oxygen, thiols and ascorbate under specific biologic conditions.
Continuous measurement of left ventricular volume in the dog. II. Comparison of washout and radiographic technics with the external dimension method.

Abstract Single plane angiocardiographic studies were performed using casts of the left ventricular cavity of the canine heart. Good agreement was found between true and calculated volume. End-diastolic volume estimated (EDV) from angiocardiographic measurements and that estimated with a method based on external cross-sectional areas and length (EAL), calibrated in each subject, correlate within 10 per cent. These data support the validity of either model. However, at end-systole, x-ray calculations always yielded an underestimation of the volume when compared with measurements by the EAL method. Immediate changes in ventricular dynamics were studied during and after the injection of 1.0 ml./kg. of Renografin. End-diastolic and stroke volumes were found to increase. Measurements by the EAL method were also compared with those from thermal washout recordings. A systematic overestimation of EDV and underestimation of SV/EDV was found. The difference was greater at faster heart rates. A linear relation between EDV, SV and ESV was found under conditions of volume overload.
Phase I single-dose safety and pharmacokinetics clinical study of the potential cancer chemopreventive agent resveratrol.

5741 The polyphenolic phytoalexin resveratrol occurs in grapes, red wine, peanuts and various berries. It has been extensively investigated in preclinical settings as a potential cancer chemopreventive agent, and inhibits biochemical events germane to all three stages of carcinogenesis, initiation, promotion and progression. Resveratrol predominantly demonstrates such activity in vitro at concentrations above 5 μM (∼1140 ng/mL). We investigated the pharmacokinetics and safety of a single oral dose of resveratrol (1.0, 2.5 or 5.0 g) in 29 healthy volunteers, in order to test the hypothesis that pharmacologically active concentrations are attainable in the plasma. Volunteers were on a resveratrol-free diet for 5 days prior to oral administration of resveratrol. Plasma and urine concentrations of resveratrol and its metabolites were monitored over a 24 h period. No serious adverse events or side effects documented by the volunteers were reported. In preliminary results (29 of 40 volunteers), AUC and Cmax of resveratrol appeared to increase in a less than dose proportional fashion (Table 1) within this dose range with greater than 50% inter-subject variability. Urinary excretion rate was maximal within 4 h post dose for all groups and the mean fraction of unchanged resveratrol excreted in urine was negligible (
On-Line Fault Resilience Through Gracefully Degradable ASICs

We present two novel reconfiguration schemes, L/U reconfiguration and its generalization, band reconfiguration, to achieve graceful degradation for general microarchitecture datapaths. Upon detection of a datapath fault, hardware and algorithmic reconfigurations are performed dynamically through operation rescheduling and hardware rebinding. Instead of a complete shuffling, the proposed scheme perturbs the original schedule and binding in a systematic fashion. This regularity of the scheme allows well-structured design planning for the controller and the datapath. The underlying microarchitecture supporting such reconfiguration schemes is briefly outlined. Experimental evidence indicates negligible performance and small hardware overheads.
Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated Lymphoid Tissue (PALT) in the chicken

Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle. PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+ (80%) with the remaining 20% comprising B-cells and monocytes (Bu-1+), which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+ (75–80%), CD8+ (20–25%), TCRαβ/Vβ1+ (60%), and TCRγδ+ (15%). All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+ and TCRγδ+/TCRαβ/Vβ1+ within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and TCRγδ+/TCRαβ/Vβ1+ each approximated 1:4. Bu-1+ cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+ microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRαβ/Vβ1+ cells, and a decline in the area density of Bu-1+ microglia at the light:dark interphase (1900 h) compared to the dark:light interphase (0700 h). The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light:dark cycle and that CD8+ and TCRγδ+ T-cells are preferentially recruited to the pineal follicles. Pineal microglia/macrophages were common and represent an important candidate for mediating these lymphocyte-pineal interactions via secretion of cytokines and chemokines.
Computational complexity and implementation of two-level plane wave time domain algorithm for scalar wave equation

Integral equation based techniques, such as the method of moments (MOM), have been widely used to analyze time harmonic surface scattering phenomena. Unfortunately, time domain counterparts of the MOM, often referred to as marching-on-in-time (MOT) schemes, have historically received scant attention. Classical MOT schemes (i) have long been conceived as intrinsically unstable, and (ii) suffer from a high computational complexity. It is well-known that the computational complexity of the MoM can be reduced by the fast multipole method. A similar time domain algorithm, namely the plane wave time domain (PWTD) algorithm, has been introduced. The PWTD algorithm is designed to be used in tandem with the conventional MOT scheme in either a two-level or a multilevel setting. This paper describes the practical implementation of the two-level scheme and demonstrates the reduction in computational complexity achieved by using the PWTD algorithm. Although the PWTD scheme is applicable to a variety of integral equations arising from the analysis of wave phenomena, this paper illustrates its application in the context of scalar wave scattering from surfaces on which Neumann boundary conditions are enforced-a problem of interest in many disciplines.
Beneficial actions of neurotrophin treatment on diabetes-induced hypoalgesia in mice.

Abstract Studies were carried out in streptozotocin-treated diabetic mice to evaluate their behavioral responses to different noxious stimuli. In opposition to rats, streptozotocin-injected diabetic mice display a persistent hypoalgesia to non-noxious mechanical stimulation (von Frey monofilament). Similarly, nocifensive responses of diabetic mice to formalin injection were significantly reduced in both acute and inflammatory phases. However, no overt differences were detected between nondiabetic and diabetic mice in their sensitivity to noxious heat (radiant heat), cold (acetone), or noxious mechanical (pinprick) stimuli applied to the hind paw. To evaluate whether neurotrophin treatment could normalize the sensory deficits, nerve growth factor (NGF) or glial cell line–derived neurotrophic factor (GDNF) was administered intrathecally to diabetic mice for 3 weeks. Neurotrophin-treated mice were also compared to mice that received insulin for 3 weeks. Both NGF and insulin treatment significantly restored mechanical and chemogenic behavioral responses of diabetic mice. In contrast, GDNF treatment only reversed behavioral responses to chemogenic stimuli during the acute phase of the formalin test. These results demonstrate that diabetic mice develop reduced sensitivity to mechanical and chemical stimuli. Furthermore, these studies show that dorsal root ganglion neurons in diabetic mice are responsive to treatment with either NGF or GDNF; however, these 2 neurotrophins differ in their ability to affect distinct somatosensations.
On Metaphysical themes: replies to critics

Calvin Normore offers a very interesting big-picture thesis about the later medieval period, one with multiple components. First, he thinks the first quarters of the thirteenth century�the era of Albert the Great and Thomas Aquinas�are �gobsmacked� by the recovery of Aristotle�s work, and hence are �anomalous.� Second he thinks that, once the gobsmacking is over, the philosophers�beginning with Peter John Olivi and onward into the fourteenth century�return to �building upon the insights of the twelfth century��that is, back to the era of Peter Abelard and others. Third, he thinks that this broader movement�what one gets if one sets aside the anomaly of Thomas Aquinas and his era�is characterized by a broader interest in the whole spectrum of ancient philosophical traditions, so that it is not just Aristotelian, but also Platonic and Stoic and Epicurean and much else. Fourth, this broadening movement sees its culmination in the seventeenth century, when the authority of ...
Barrel rotation evoked by intracerebroventricular vasopressin injections in conscious rats. I. Description and general pharmacology.

Intracerebroventricular (i.c.v.) arginine-vasopressin (AVP) injections in rats evoke an unusual motor response termed ‘barrel rotation’ (BR). This report documents several aspects of BR after i.c.v. AVP in conscious, adult male Sprange-Dawley rats: (1)_single i.c.v. AVP injections (100–1000 ng/5 υl) evoke BR in about of naive rats with no relatioship to dose and 20% mortatily; (2) no directional preference exists for BR, and sensitivity to BR does not vary over a weight range of 301–475 g; (3) continuous i.c.v. AVP infusions at doses of 50–2500 mg/h evoked BR in 13 and 50% of rats tested at the extreme ranges; latency to BR was always within 3–6 min in infusion experiments; (4) a protocol where rats received a single i.c.v. AVP injection (1 μg) on day 1 followed on day 3 by 0.5 μg, increased the proportion of rats with BR from 51% to 83% (P<0.05), indicating a sensitization phenomenon; (5) latency to BR after single i.c.v. injections did not fit the assumption of single underlying normal distribution; a novel method to analyze these data, hazard plotting, revealed two phases to the BR latency under ambient illumination. The following paper presents evidence of visual/vestibular involvement and the efficacy of anti-seizure drugs. Collectively, the data are compatible with the hypothesis that brain vasopressin pathways are involved in some abnormalities of motor output.
Lorazepam in the Treatment of Refractory Neonatal Seizures

We report the results of treatment of intractable seizures with lorazepam in seven neonates. All of the patients were part of a prospective study, who failed to respond to 40 mg/k of phenobarbital. Lorazepam was given intravenously at 0.05 mg/k and repeated up to a total dose of 0.15 mg/k if necessary. The diagnosis of seizures and the efficacy of treatment was assessed clinically and by EEG during the administration of lorazepam in three patients and on clinical grounds in four patients. Six patients were full term and one was premature; there were five males and two females. Four patients had hypoxic-ischemic encephalopathy, two had intracranial hemorrhage, and one had bacterial meningitis. Two patients received one dose of lorazepam, three received two doses, and two received three doses. Six patients responded with a complete cessation of seizures within three minutes of their last dose; the remaining patient (who received two doses) had a reduction in seizures. No patients developed apnea or hypotension during or immediately after the infusion of lorazepam and no other adverse effects were observed. Four patients remained seizure-free for the rest of the neonatal period and no other anticonvulsant medications were added. Seizures recurred in one patient at 16 hours; subsequent intermittent seizures were managed with additional phenobarbital. In another patient, seizures recurred at 12 hours and subsequent intermittent seizures were managed with phenytoin. In one patient, seizures continued with reduction of frequency and duration. We conclude that lorazepam may be effective in the treatment of neonatal seizures refractory to phenobarbital and that further treatment with intravenous phenytoin may be unnecessary under these circumstances.
Elevation of endogenous nucleophiles in rat lung by cysteine and glutathione esters in vitro.

Abstract In this study, we have compared the uptake of l -cysteine ( l -CySH), d -cysteine ( d -CySH), l -cysteine isopropyl ester ( l -CIPE) and d -cysteine isopropyl ester ( d -CIPE) in rat lung slices and tracheal sections and determined the effectiveness of glutathione (GSH), GSH isopropyl monoester, GSH isopropyl diester, γ-glutamylcysteine (γ-glu-cys) isopropyl monoester and γ-glu-cys isopropyl diester to elevate and prolong intracellular GSH concentrations in rat lung slices. Lung slices were incubated with 1.0 mM of thiol and the concentrations determined intracellularly and extracellularly with time. Slices incubated with GSH, GSH isopropyl diester and γ-glu-cys isopropyl diester had cellular GSH concentrations increased by up to 60%, 95% and 58%, respectively, whereas GSH isopropyl monoester and γ-glu-cys isopropyl monoester did not increase the intracellular GSH concentration. Extracellularly, the GSH concentration had decreased by 15%, GSH isopropyl diester by 27%, γ-glu-cys isopropyl diester by 66% and both isopropyl monoesters by over 90% at 120 min. Lung slices and tracheal sections incubated with l - or d -CySH at 37° had increased cellular concentrations of l - and d -CySH which ranged between 0.88–1.25 nmol mg −1 and 1.35–2.25 nmol mg −1 , respectively. Reducing the incubation temperature to 4° had little effect on the accumulation of d -CySH; however, l -CySH concentrations increased progressively in the trachea and lung to reach 2.73 and 2.63 nmol mg −1 at 90 min, respectively. Lung slices incubated with l - or d -CIPE had increased l - or d -CySH concentrations up to a max of 13.7 and 11.1 nmol mg −1 and tracheal sections up to a max of 5.56 and 11.09 nmol mg −1 . In the lung slice medium, l - and d -CIPE levels had decreased by 75.2% and 74.0% at 90 min, respectively, and from the tracheal section medium, l - and d -CIPE concentrations had decreased by 66.7% and 32.7%, respectively. Preincubation of lung slices and tracheal sections with the carboxylesterase inhibitor, bis ( p -nitrophenyl) phosphate (BNPP), almost completely prevented the disappearance of l - and d -CIPE extracellularly and greatly reduced the appearance of cellular l - and d -CySH. GSH, GSH isopropyl diester and γ-glu-cys isopropyl diester elevated and prolonged GSH concentrations in rat lung slices, but GSH isopropyl monoester and γ-glu-cys isopropyl monoester did not increase GSH levels. The uptake of l -CySH, but not d -CySH, is temperature sensitive in rat lung slices and tracheal sections and carboxylesterases appear to have a major influence on the uptake and metabolism of l - and d -CIPE by rat lung slices and tracheal sections.
Water Waves Over Ripples

The interaction of small amplitude water waves with a patch of bottom ripples is studied using the Boundary Integral Equation Method (BIEM). Normal and oblique wave incidence is examined for reflection coefficients and the laboratory data of Davies and Heathershaw are compared to the numerical results, with the conclusion that the analytical model of Davies and Heathershaw overestimates the reflection coefficient at resonance. Comparison of BIEM results for oblique incidence is made with an extension of the recent work of Mei showing good agreement, even for large amplitude ripples.