cssi/SciSciGPT-SciSciNet huggingface dataset:
Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure

Increased accumulation of manganese (Mn) in the brain is significantly associated with neurobehavioral deficits and impaired brain function. Airborne Mn has a high systemic bioavailability and can be directly taken up into the brain, making it highly neurotoxic. While Mn transport is in part mediated by several iron transporters, the expression of these transporters is altered by the iron regulatory gene, HFE. Mutations in the HFE gene are the major cause of the iron overload disorder, hereditary hemochromatosis, one of the prevalent genetic diseases in humans. However, whether or not HFE mutation modifies Mn-induced neurotoxicity has not been evaluated. Therefore, our goal was to define the role of HFE mutation in Mn deposition in the brain and the resultant neurotoxic effects after olfactory Mn exposure. Mice carrying the H67D HFE mutation, which is homologous to the H63D mutation in humans, and their control, wild-type mice, were intranasally instilled with MnCl2 with different doses (0, 0.2, 1.0 and 5.0 mg kg(-1)) daily for 3 days. Mn levels in the blood, liver and brain were determined using inductively-coupled plasma mass spectrometry (ICP-MS). H67D mutant mice showed significantly lower Mn levels in the blood, liver, and most brain regions, especially in the striatum, while mice fed an iron-overload diet did not. Moreover, mRNA expression of ferroportin, an essential exporter of iron and Mn, was up-regulated in the striatum. In addition, the levels of isoprostane, a marker of lipid peroxidation, were increased in the striatum after Mn exposure in wild-type mice, but were unchanged in H67D mice. Together, our results suggest that the H67D mutation provides decreased susceptibility to Mn accumulation in the brain and neurotoxicity induced by inhaled Mn.
Closure of a Recurrent Bronchopleural Fistula Using a Matrix Seeded With Patient-Derived Mesenchymal Stem Cells

: Management of recurrent bronchopleural fistula (BPF) after pneumonectomy remains a challenge. Although a variety of devices and techniques have been described, definitive management usually involves closure of the fistula tract through surgical intervention. Standard surgical approaches for BPF incur significant morbidity and mortality and are not reliably or uniformly successful. We describe the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to repair a multiply recurrent postpneumonectomy BPF. Adipose-derived MSCs were isolated from patient abdominal adipose tissue, expanded, and seeded onto bio-absorbable mesh, which was surgically implanted at the site of BPF. Clinical follow-up and postprocedural radiological and bronchoscopic imaging were performed to ensure BPF closure, and in vitro stemness characterization of patient-specific MSCs was performed. The patient remained clinically asymptomatic without evidence of recurrence on bronchoscopy at 3 months, computed tomographic imaging at 16 months, and clinical follow-up of 1.5 years. There is no evidence of malignant degeneration of MSC populations in situ, and the patient-derived MSCs were capable of differentiating into adipocytes, chondrocytes, and osteocytes using established protocols. Isolation and expansion of autologous MSCs derived from patients in a malnourished, deconditioned state is possible. Successful closure and safety data for this approach suggest the potential for an expanded study of the role of autologous MSCs in regenerative surgical applications for BPF. Significance Bronchopleural fistula is a severe complication of pulmonary resection. Current management is not reliably successful. This work describes the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to the repair of a large, multiply recurrent postpneumonectomy BPF. Clinical follow-up of 1.5 years without recurrence suggests initial safety and feasibility of this approach. Further assessment of MSC grafts in these difficult clinical scenarios requires expanded study.
The Working of the Anti-Monopoly Law in India: an Exploratory Study and some Comparative Insights

Comprehensive antimonopoly legislation is still a rarity in the Third World countries. India is one of the few Third World Countries which has a fairly elaborate law relating to monopolies and restrictive trade practices. This paper examines the working of this law by analyzing 29 cases decided in the first four years the law was in operation. Conclusions are drawn about the scope and manner of application of India’s anti-monopoly law and its impact on competitive practices. Broad comparisons are made with the antitrust laws of developed and developing countries. The problem of what is an appropriate industrial and competitive policy for Third World countries is placed in a perspective.
Magnetic minerals as recorders of weathering, diagenesis, and paleoclimate: A core–outcrop comparison of Paleocene–Eocene paleosols in the Bighorn Basin, WY, USA

Abstract Magnetic minerals in paleosols hold important clues to the environmental conditions in which the original soil formed. However, efforts to quantify parameters such as mean annual precipitation (MAP) using magnetic properties are still in their infancy. Here, we test the idea that diagenetic processes and surficial weathering affect the magnetic minerals preserved in paleosols, particularly in pre-Quaternary systems that have received far less attention compared to more recent soils and paleosols. We evaluate the magnetic properties of non-loessic paleosols across the Paleocene–Eocene Thermal Maximum (a short-term global warming episode that occurred at 55.5 Ma) in the Bighorn Basin, WY. We compare data from nine paleosol layers sampled from outcrop, each of which has been exposed to surficial weathering, to the equivalent paleosols sampled from drill core, all of which are preserved below a pervasive surficial weathering front and are presumed to be unweathered. Comparisons reveal an increase in magnetization in outcrops compared with core equivalents, which is principally driven by secondary hematite production. Authigenic hematite production in outcrops presents a complication for goethite–hematite based paleoprecipitation proxies where estimates will be biased toward drier climate regimes. The occurrence of low coercivity minerals is more consistent between core and outcrop. However, we propose an alteration process for pedogenic magnetite that is observed in both core and outcrop, where pedogenic magnetite becomes progressively oxidized leading to higher mean coercivities and broader coercivity distributions compared to modern pedogenic magnetite. This combination of diagenetic processes and surface weathering influences the magnetic properties of paleosols. Despite these changes, magnetic enhancement ratios from B-horizons correlate with independent MAP estimates from geochemical proxies, which suggests that paleoprecipitation information is preserved. Future work should continue to address these complications by developing useful protocols that isolate the magnetic properties that are most resistant to alteration and remain strong indicators of MAP and climate.
Transposable elements and evolution

On June 27 & 28, 1992, a distinguished group of 25 molecular, population and evolutionary geneticists assembled on the campus of the University of Georgia in Athens to discuss the relevance of their research to the role played by transposable elements (TEs) in evolution. The meeting consisted of a series of informal discussions of issues brought up in papers written by the participants and distributed among them prior to the meeting. These papers and transcripts of the ensuing discussions are presented in this volume. Three additional papers (Boussy & Periquet; McDonald & Cuticchia; Lankenau) related to the topic of TEs and evolution but not presented at the meeting are also included in this volume. My purpose in organizing this meeting was to bring together individuals representing diverse scientific backgrounds and interests whose work has, nevertheless, led them to the tentative conclusion that TEs may be playing a role in the evolution of genome structures and functions.
Effect of CTCAE v4 grading of hypertension on reported toxicity in advanced cancer patients receiving vascular endothelial growth factor (VEGF)-targeting agents.

e15600 Background: The NCI Common Terminology Criteria for Adverse Events (CTCAE) system changed to version 4 in 2009, and several AE categories underwent changes in grading (Gr), including HTN. As...
Lysophosphatidic Acid Promotes a Switch from Nitric Oxide to Hydrogen Peroxide as the Mediator of Flow-Induced Dilation in Human Arterioles

IntroductionMicrovascular dysfunction is strongly predictive of cardiovascular pathology. Previous studies in our laboratory have shown that flow-induced dilation (FID) in patients with coronary ar...
Resilient First-Order Consensus and Weakly Stable, Higher Order Synchronization of Continuous-Time Networked Multiagent Systems

Local interaction rules for consensus and synchronization are vital for many applications in distributed control of cyber-physical systems. However, most research in this area assumes all nodes (or agents) in the networked system cooperate. This paper considers local interaction rules for resilient first-order consensus and weakly stable, higher order synchronization whenever some of the agents in the network are Byzantine-like adversaries defined in a continuous-time setting. The normal agents have identical dynamics modeled by continuous-time, linear, time-invariant, weakly stable systems. Agents in the networked system influence one another by sharing state or output information according to a directed, time-varying graph. We present a resilient consensus protocol as well as dynamic state and output feedback control laws for the normal agents, to achieve the resilient consensus and synchronization objectives, respectively. We characterize the required network topologies using the property of network robustness. We demonstrate the results in simulation examples to illustrate the resilient synchronization output feedback control law.
Nurse-driven protocols and the prevention of catheter-associated urinary tract infections: A systematic review.

Background Catheter-associated urinary tract infections (CAUTIs) are one of the most common hospital-acquired conditions and no longer reimbursable from Medicare as of 2008. Nurse-driven protocols (NDPs), which provide a medically approved rubric for professional nurses to make autonomous care decisions, can facilitate appropriate catheter use and timely removal, as advised in the Centers for Disease Control and Prevention's 2009 CAUTI prevention guidelines. However, little attempt has been made to systematically evaluate their effect on clinical outcomes. Methods A systematic review of studies published in the United States since 2006 was performed, following guidelines from the Institute of Medicine. Sources included CINAHL, Medline, professional agencies, hand-searching, and expert consultation. Clinical predictors and prevalence of CAUTI were examined and synthesized qualitatively; heterogeneity of outcomes made a statistical meta-analysis inappropriate. Results Twenty-nine studies were found eligible for inclusion. All used a case-control (pre-post) approach, and all reported reductions in clinical predictors of CAUTI, particularly indwelling-urinary catheter utilization and CAUTI rates. However, the number of CAUTIs remained unchanged in 1 study. A formal quality assessment revealed a high risk of bias; included studies met an average of 4.9 out of 11 quality indicators. Specifically, many did not use standardized measures. Conclusions NDPs appear to have a positive impact on the clinical predictors and prevalence of CAUTI. However, this review identified need for improving the study design of quality improvement projects conducted within the patient care setting.
An economic analysis of cucumber (Cucumis sativus L.) cultivation in eastern zone of Haryana (India) under polyhouse and open field condition

The study was conducted in north zone of Haryana (India) state to find out the economic analysis of cucumber cultivation under polyhouse and open field condition. The primary data was collected by personal interview of the selected respondents with the help of well-designed and pre tested schedule. Simple statistical tools like average and percentage were used to calculate the economics of the crop. In the present study, it was found that the cost of cultivation of cucumber per acre under polyhouse was Rs. 283684.40 while in case of open field condition it was Rs. 98003.39. In case of production and net returns, it was higher per acre in polyhouse; 245.47 quintal and Rs. 97138.68, respectively. Present study concluded that yield and income of farmers can be increased with help of polyhouse technology in case of cucumber cultivation.
Contrast-enhanced or noncontrast CT for renal colic: utilizing urinalysis and patient history of urolithiasis to decide

In the emergency setting, flank pain commonly leads to a noncontrast CT despite a significant percentage of patients having alternative diagnoses, often difficult to characterize without contrast. We investigated the combined utility of urinalysis and history of urolithiasis in identifying patients who are unlikely to have urolithiasis and may benefit from a contrast-enhanced study. Retrospective review of 350 patients from May 2013 to May 2016 was performed for patients in the emergency department with renal colic that underwent noncontrast CT and urinalysis testing. Urolithiasis was present in 282 of the 350 patients reviewed (81%), of which 175 (62%) had an obstructing calculus. RBC-positive urinalysis was present in 231 patients with calculi on CT (sensitivity 82%). Patient history of urolithiasis plus urinalysis had a sensitivity of 94% for detecting calculi. Thirty-five patients (10%) had alternative diagnoses, 33 of which were in patients without obstructing calculi. Sixty-seven patients underwent noncontrast CT despite no history of urolithiasis and a negative urinalysis, 10 of which (15%) had alternative diagnoses. Only three cases in this subset (4%) had nonobstructing 1–2-mm calculi, potentially missed with contrast. In this subset, the projected proportion of optimally characterized cases with intravenous contrast is 96%, compared to 85% without contrast (p = .03). Given the high combined sensitivity of urinalysis and patient history (94%), this simple analysis can confidently direct clinicians to a contrast-enhanced CT in “rule-out” cases of flank pain in patients with a negative history and negative urinalysis, particularly given that 15% of these patients had alternative diagnoses.
A monoclonal antibody specific to Müller cells and selective synaptic sites in the retina.

We have produced a monoclonal antibody which stains the Muller cells in the region of the photoreceptors, nerve terminals surrounding the horizontal cells, and nerve terminals in the inner plexiform layer in carp, goldfish, and white perch retinas. Electron microscopy showed that the staining in the outer and inner retina was confined to Muller cells and presynaptic terminals, respectively. In the teleost brain, the antibody stained only the optic tectum and efferent fibers from the stratum album centrale. Biochemical characterization by immunoblotting showed that this monoclonal antibody recognizes an approximately 70-kD molecule in both whole retina and brain homogenates, suggesting that the antibody recognizes an identical molecule. No staining was noted in the spleen or the liver. This monoclonal antibody appears to be specific to a molecule common to the Muller cells and presynaptic terminals in the teleost retina, and although it is present in other parts of the central nervous system, it is confined to the visual pathway.
Perspectives on Archival Resources: The 1985 Census of Archival Institutions

This article is a report on the first comprehensive survey of the resources, responsibilities, and activities of archival repositories in the United States. After placing the study in the context of past surveys of archivists and institutions, and describing its design, the article characterizes the findings on five basic resources common to all archives—money, staff, holdings, facilities, and users. Summary tables permit comparisons of the responses to key survey questions across eight types of archives—federal, state, local, academic, religious, business, special subject, and museum. The author concludes with recommendations for improving future studies.
Morphological variations in ulnar supinator crests and fossae as identifying markers of occupational stress.

Recent morphometric studies of ulnae of prehistoric skeletal remains from populations known to have used spears, atlatls, and similar projectile weapons for hunting and warfare reveal a high incidence of hypertrophy of the ulnar crest, to which the supinator muscle is attached, along with pronounced depth of the adjacent supinator fossa, especially in the upper extremities of males. Similar features occur in the right ulnae of living persons of both sexes who are habitually engaged in certain occupational and athletic activities involving angular displacement of the forearm as a result of medial rotation of the arm at the shoulder, shoulder and arm rapid extension, and abrupt shifts from forearm supination to pronation. Aside from its forensic science implications in determination of right- or left-handedness as a trait peculiar to the individual, observation of these markers of stress on the proximal end of the ulna are significant in identification of skeletal remains of persons known to have engaged in specific brachial activities during life. The hiomechanics of these movement patterns and activities in which they occur, when properly interpreted, are relevant to forensic science problems of individual identification and paleoanthropological studies of occupational stress factors in extinct populations for which a skeletal record is available.
Distributed Computing Column 72: Annual Review 2018

As with prior December issues, this issue is devoted to a review of notable events related to distributed computing that occurred during the year.First, congratulations to Bowen Alpern and Fred Schneider, winners of the 2018 Edsger W. Dijkstra Prize in Distributed Computing for their paper \De ning Liveness"! Their paper appeared in Information Processing Letters in October 1985. The prize is jointly sponsored by ACM and EATCS, and is given alternately at PODC1 and DISC2; this year it was given at PODC. This paper formally de ned liveness properties of concurrent and distributed algorithms for the rst time and also proved that every trace property is the conjunction of a safety property and a liveness property. The full citation can be found at http://www.podc.org/dijkstra/2018-dijkstra-prize/. I am delighted to include in this column the text of the remarks that Fred and Bowen gave at PODC when the award was presented to them.
Use of Stimulants for ADHD and TBI in Veterans

Stimulants are an important psycho-pharmacological tool to consider when treating veterans with adult ADHD and TBI and as a second-line agent for narcolepsy or excessive daytime sedation. Stimulants may also have a role in helping veterans with dementia-related cognitive changes such as apathy or treatment-refractory depression; however, there is less evidence supporting their role for these conditions. In use since the early 1900s, many stimulant formulations currently available can be very effective and relatively quick acting agents. However, caution must be used in veterans with significant cardiac risk factors and females of childbearing age as well as those at risk for substance use disorders, eating disorders, mania, and psychosis. In this chapter, the authors review the most common psychiatric conditions for which stimulants may be indicated in veterans as well as tips for successful prescribing practices, monitoring ongoing use as well as potential pitfalls and contraindications.
Parenting the Parents: The Ethics of Parent-Targeted Paternalism in the Context of Anti-poverty Policies

Governments often aim to improve children’s wellbeing by targeting the decision-making of their parents. In this paper, I explore this phenomenon, providing an ethical evaluation of the ways in which governments target parental decision-making in the context of anti-poverty policies. I first introduce and motivate the concept of parent-targeted paternalism to categorize such policies. I then investigate whether parent-targeted paternalism is ever pro tanto wrong, arguing that it is when directed at parents who meet a threshold of parental competency. I next explore the factors that affect the degree of pro tanto wrongness of paternalistic anti-poverty policies targeting parents, and provide an account of the conditions under which such policies are on balance permissible, and when they are not. Finally, I illustrate the plausibility and usefulness of my framework by considering a case.
Visual Feedback is Not Important for Bimanual Human Interval Timing

The clock variance of intervals produced by one finger is reduced when that finger taps along with another finger (termed the bimanual advantage). The multiple-timekeeper model proposes a coupling of internal clocks, leading to reduced clock variance for bimanual timing. Alternatively, reduced variance for bimanual timing could result from additional sensory feedback from two fingers as opposed to one. We aimed to test the role of visual feedback in reducing temporal variability. Participants tapped unimanually and bimanually (with no table contact) in three conditions: full vision, blindfolded, and with additional visual feedback provided via a mirror reflecting the right hand. We predicted that temporal variability would be reduced for tapping with vision versus no vision, and when the left hand was represented by a mirror but did not actually tap. Additional, redundant visual information did not reduce temporal variability for any condition, suggesting that visual feedback is not crucial for bimanual advantage. These findings support the role of sensory feedback (namely, tactile, auditory, and proprioceptive) in reducing timekeeper variability during bimanual timing and argue against a strictly multiple-timekeeper model.
Review of Penelope Deutscher, Foucault’s Futures: A Critique of Reproductive Reason

In Foucault’s Futures: A Critique of Reproductive Reason, Penelope Deutscher explores the “suspended reserves” in Foucault’s writing, “absent concepts and problems [that] can be given a shape in potentially transformative ways within philosophical frameworks which have omitted them Deutscher (Deutscher 2017, p. 5).” Deutscher pays particular attention to neglected figures of children in Foucault’s works and she develops the notion of “responsibilization,” processes of dividing populations into legible and illegible reproductive moral agents. This review of Foucault’s Futures considers Deutscher’s methodological innovation as it relates to Foucault’s own method of genealogy. While the notion of “suspended reserves” risks privileging the academic over the “wide cultural surfaces” of power, Foucault’s Futures provokes a queer critical ethics against ongoing violence of responsibilization.
Application of blood products and immunological support therapy for severe sepsis

Severe sepsis and septic shock is a clinical syndrome with sequential organ dysfunction or tissue hypoperfusion induce by sepsis. Although early, adequately and rapidly initial resuscitation plays pivotal role in the management, but infusion of albumin, plasma, red blood cell, platelet, gamma globulin and other blood products and the immunological support with ulinastatin combined with thymosin, blood purification and anti CD14 monoclonal antibody therapy also play an important role. Key words: Sepsis; Blood products; Immunological support
Contagion and war: lessons from the First World War

The centennial of the First World War has produced a mass of excellent scholarship on the war. It might come as a surprise to some that not all of this scholarship has been in the field of history....
Qohelet’s Implied Author and Implied Readers:

Qohelet is not only an anthology of journalings or an exposition of an individual’s agonizings; it is also (perhaps more) a book of teaching and a piece of rhetoric. It aims to disturb the assumpti...
What Can the Chemical Hold?: The Politics of Efficacy in the Psychedelic Renaissance

Drawing from ethnographic research with psychedelic therapists and researchers, this article explores political tensions between two sources of efficacy within psychedelic therapy: the self and the chemical. At times researchers and therapists emphasize the specificity of chemical effects in relationship to the neurobiology of particular diagnoses. And at other times they foreground the self as the true source of an experience which is not tied to that same biochemistry. Anthropologists have long emphasized that efficacy is a historically and socially embedded category and practice. Those conversations have new valence in light of recent theorization of the chemicals as material-semiotic structures shaped by their experimental contexts. This article argues that while the empirical claims embedded in these two efficacies can and do mutually include each other, a fundamental political tension remains between the efficacious ends envisioned by each. As clinical trials develop these drugs as therapeutic agents, they do so through linking the specific effects of the chemical to particular diagnostic populations, which may enfranchise these chemicals, but not all their efficacies.
Desynchronization of jammed oscillators by avalanches

This work shows that the addition of short-range repulsion to classical coupled oscillators leads to continuous avalanche-like cascades, preventing synchronization.
The Spectra of Molecular Solids

Publisher Summary This chapter focuses on the spectra of molecular solids, explaining intensities of intra-molecular vibrational spectra. The original incentive to the development of the field of infrared spectroscopy of molecular crystals was twofold. On one hand, it seemed promising to study the absorption spectra of single-oriented crystals in polarized light to obtain information helpful for the assignment of intra-molecular vibrations. Because the molecules in the crystal are rigidly fixed in space, it was thought that it should be possible to relate the results of polarized light investigations to the symmetry of the vibration observed. The vibrational exciton theory was based on the electronic exciton theory of molecular solids. In this case, the first attempts at quantitative calculations were made for an intermolecular potential that was expanded in a multipole series retaining the first term, the dipole–dipole term. It is concluded that for intense infrared transitions, the splitting energies observed are to a large degree accounted for by the dipole interaction approximation.
Initial Studies of Neutron-Rich Nuclei with Next-Generation Radioactive Beam Facilities

Unprecedented opportunities to extend the horizons of nuclear physics towards the “terra incognita” of neutron rich nuclei await the advent of next generation radioactive nuclear beam (RNB) machines, such as the Rare Isotope Accelerator (RIA) project. However, beam intensities, especially at the boundaries of accessibility, will be many orders of magnitude weaker than we are accustomed to. To overcome this obstacle and exploit the potential opportunities requires significant improvements in detectors systems and parallel improvements in our ability to extract more nuclear structure information from less data.
Fighting for Thirlmere--The Roots of Environmentalism

The seeds of environmental activism sprouted during the 19th century in the highly scenic Lake District of northwest England. Here, tensions were played out between the need for new freshwater supplies for the growing industrial metropolis of Manchester and the desire of the Lake District inhabitants and landowners not to have their romantic landscape despoiled.
Aqueous lateral epitaxy overgrowth of ZnO on (0001 ) GaN at 90 °C Part II: Stress determination

Abstract In Part I, it was shown that the critical thickness required for mechanical failure of lateral epitaxial overgrown films of ZnO on GaN buffered Al 2 O 3 substrates could be significantly increased by masking and patterning the substrate to produce periodic, hexagonal arrays of circular windows. It was also observed that the critical thickness could be increased by increasing the distance between the circular windows. In Part II, it is shown, using Raman piezo-spectroscopy, that a stress gradient exists within the hexagonal prisms of ZnO that grow from the circular windows. The compressive stress, due to lattice mismatch, was highest in the center of the prisms and lowest near the perimeter where they overgrow the masked region to form ‘wings’. For one orientation of the hexagonal array of circular windows, relative to the substrate, where the hexagonal prism coalesce face to face, the stress gradient persisted after the hexagonal prisms coalesced to form a continuous film because residual voids surround the base of the coalesced, hexagonal prisms. For a second orientation where the hexagonal prisms coalesce corner to corner, the stress gradient was greatly diminished due to a larger amount of coalescence at the base of the prisms. Most important, it was shown that the compressive stress for both arrays decreased with increased spacing between the circular windows. Namely, for window orientation producing face to face coalescence of the prisms, the maximum compressive stress decreases from ∼ 520 MPa for windows separated by twice their diameter to ∼ 350 MPa for windows separated by four times their diameter. These results are consistent with the critical thickness observations reported in Part I.
The Libration Case of the Stellar Problem of Three Bodies

The methods of nonlinear mechanics are introduced to facilitate the study of the libration case of the stellar problem of three bodies. To illustrate the method, the problem of a lunar satellite perturbed by the earth and under the influence of the J 2 and J 3 terms of the moon’s gravitational field is considered. By means of the energy integral and the equation of motion of the argument of pericenter, a closed curve is obtained in phase space. Analysis of the geometry of the variables in phase space yield the period of libration and expansions of the argument of pericenter and eccentricity in terms of time.
How Secularists Helped Knock Down the Wall of Separation between Church and State

An increasingly common view maintains that the legendary wall of separation between church and state has fallen into a state of serious disrepair. There is also a widely voiced opinion about who deserves the blame, or the credit, for this development: the people ostensibly responsible for the wall's decline are religious conservatives, working through and upon the Republican Party and Republican appointees to the federal bench. In this article, I argue that this ascription of responsibility is fundamentally misleading. Complacently offered or accepted, it does a serious disservice to our understanding of the long-term causal influences that have combined to subvert the commitment to church-state separation and also, more generally, to our understanding of the situation we currently occupy and the prospects that may be available to us. Indeed, from a more detached perspective, the diagnosis ascribing the decay of the wall of separation to religious believers and their political representatives is almost exactly wrong. It would be more accurate, ultimately, to attribute the declining fortunes of the wall - and the principle of separation - to secularists and secular influences (in a modern sense of the term) than to religion. Part I of the article (Foundations: Separation and the Classical 'Secular') attempts to explain three things: what 'secular' meant in its premodern or classical sense, how the 'secular' in that classical sense gave rise to a jurisdictional question affecting church and state, and how a commitment to 'separation of church and state' and a derivative commitment to freedom of conscience expressed the generally shared classical response to that jurisdictional question. Part II (Dissolution: Separation, Conscience, and the Modern 'Secular') follows the same order, attempting to explain how the concept of the secular was transformed into its modern sense of 'not religious', how the modern sense of the secular dissolved the earlier question of jurisdiction and replaced it with a question of justice, and how this transformation has altered and significantly undermined the classical commitments to separation of church and state and freedom of conscience. Part III (Phasing out the Wall) discusses the stages in which the reduction of the wall - of the commitments to separation of church and state and freedom of conscience - has proceeded in modern American jurisprudence. The Conclusion reflects briefly on the alternatives that may be available to us now.
Selenium Requirements of Rats for Normal Hepatic and Thyroidal 5′-Deiodinase (Type I) Activities

The nutritional requirement of selenium for type I 5'-deiodinase activity in thyroid compared with liver was assessed in rats. Male weanling Sprague-Dawley rats were fed a torula yeast-based diet for 20 wk. One group of rats was fed the Se-deficient basal diet (0.01 mg Se/kg). The other three groups were fed the basal diet plus sodium selenite at 0.05, 0.1 and 0.5 mg Se/kg diet. Liver 5'-deiodinase and glutathione peroxidase (GSH-Px) activities were depressed in the group fed the Se-deficient (basal) diet compared with the other groups. Liver 5'-deiodinase activity in the group fed 0.05 mg Se/kg diet was as high as in the groups fed 0.1 and 0.5 mg Se/kg diet, whereas GSH-Px activities in the groups fed 0.05 and 0.1 mg Se/kg diet were intermediate in value. Feeding the Se-deficient diet for 20 wk did not cause a suppression in 5'-deiodinase in the thyroid, and thyroid GSH-Px activity was approximately 40% of that in the other groups. In rats fed Se-supplemented diets, thyroid GSH-Px was approximately 20% or less of the activity found in liver. Plasma thyroxine was higher in the group fed the Se-deficient (basal) diet, but there were no differences in plasma 3,3',5-triiodothyronine among all groups. The results suggest that the nutritional Se requirement for 5'-deiodinase is less than that for GSH-Px and is approximately 0.05 mg Se/kg in the diet for normal activity in the liver and approximately 0.01 mg Se/kg for normal activity in the thyroid. Thyroid seems to be a priority organ over liver for Se when the intake of the element is limited.
Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

Abstract Background Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non–small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Methods Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. Results With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC ( P = .005). Conclusion Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers.
Nerve growth factor (NGF) potentiates the changes in striatal proenkephalin mrnas subsequent to 6-hydroxydopamine-induced lesions of the substantia nigra

The topographical changes in proenkephalin (PEK) mRNAs which occur in the caudate-putamen (CPu) after 6-hydroxydopamine (6-OHDA)-induced unilateral lesion of the mesostriatal dopamine (DA) pathway were evaluated by quantitative in situ hybridization. These lesions caused significant increases in PEK mRNA in all regions of the caudate-putamen (CPu). The chronic intraventricular administration of NGF potentiated the increases in PEK mRNA, with the magnitude of changes being greater in the dorsomedial and dorsolateral regions of the striatum. NGF did not affect the loss of tyrosine hydroxylase mRNA observed in the substantia nigra ipsilateral to the 6-OHDA-induced lesion. These results demonstrate that alterations which occur in a neuropeptide system as a consequence to 6-OHDA-induced denervation of the striatum can respond to NGF administration in a topographical fashion.
Optimal coordination mechanisms in generalized principal–agent problems

Abstract The general principal–agent problem is formulated, in which agents have both private information and private decisions, unobservable to the principal. It is shown that the principal can restrict himself to incentive-compatible direct coordination mechanisms, in which agents report their information to the principal, who then recommends to them decisions forming a correlated equilibrium. In the finite case, optimal coordination mechanisms can be found by linear programming. Some basic issues relating to systems with many principals are also discussed. Non-cooperative equilibria between interacting principals do not necessarily exist, so quasi-equilibria are defined and shown to exist.
Impact of Vegetation on Sedimentary Organic Matter Composition and Polycyclic Aromatic Hydrocarbon Attenuation

Results from natural and engineered phytoremediation systems provide strong evidence that vegetated soils mitigate polycyclic aromatic hydrocarbon (PAH) contamination. However, the mechanisms by wh...
Sleep, circadian rhythms, and the pathogenesis of Alzheimer Disease

Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep-wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep-wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD.
Selective protection against the cytotoxicity of methotrexate and methotrexate-poly(lysine) by thiamine pyrophosphate, heparin and leucovorin.

Abstract The cytotoxicity of both methotrexate (MTX) and methotrexate-poly(L-lysine) conjugate (MTX-poly(lys)) on L929 mouse fibroblasts can be prevented by the simultaneous administration of Leucovorin. Thiamine pyrophosphate, an inhibitor for MTX-transport, protects cells from the toxicity of MTX, but not of MTX-poly(lys). Heparin at low concentration (1 μg/m1) completely abolishes the toxic effect of MTX-poly(lys), but not of MTX. These results suggest that although MTX and MTX-poly(lys) share the same mode of drug action inside the cell, they possess completely different transport mechanisms at the cell surface. The protection of cells by heparin against MTX-poly(lys) is biphasic, i.e. at higher heparin concentration (>10 μg/m1) the cytotoxicity can be partially restored. This observation suggests that this polyanion may have cellular effects other than neutralizing the positive charges on the drug carrier poly(lysine).
Incidence of implant buccal plate fenestration in the esthetic zone: a cone beam computed tomography study.

Purpose: The aim of this cone beam computed tomography (CBCT) study was to investigate the incidence of fenestration and associated risk factors with virtual placement of an implant in the maxillary incisor region. Materials and Methods: Edentulous ridges missing a maxillary central or lateral incisor and amenable for single implant placement were included. Root-form implants (4 × 12 mm and 3.5 × 12 mm for the central and lateral incisors, respectively) were placed virtually in the edentulous space following the axis of the ipsilateral crown. Buccolingually, the implants were placed in the ideal prosthetic cingulum position. The angles of the ridge (RA) and implants (IA) in relation to the hard palate and the incidence of fenestration were recorded. Results: A total of 48 CBCT scans were analyzed. The mean RA and IA were 124.32 degrees and 110.91 degrees, respectively. Nine cases resulted in fenestration, equivalent to 18.75% of the total cases. The discrepancy between the RA and IA was statistically significantly larger in the fenestration sites (19.93 degrees) than in the nonfenestration sites (13.05 degrees). The concavity depth of the alveolar ridge was statistically significantly higher in the fenestration sites (4.79 mm) than in the nonfenestration sites (3.40 mm). Conclusion: Within the limitations of this study, it can be concluded that the occurrence of fenestration is common (approximately 20%) if an implant is placed in the cingulum position with the axis following that of its restoration.
Antigen processing and presentation to T cells.

In this article Howard Grey and Robert Chesnut describe recent insights into the mechanism of antigen presentation and discuss the needfor antigen processing in the stimulation of T cells.
Experimental and analytical studies on fixed mask assembly for APS with enhanced cooling

The Advanced Photon Source (APS) to be constructed at Argonne National Laboratory (ANL) utilizes magnetic devices which generate X-ray beams with very intense heat flux levels. The Fixed Mask Assembly (FMA) is the first component to interact with the X-ray beam. Two sets of a pair of FMA channels vertically and horizontally disposed contain the beam rather than define it. They are subject to very large heat fluxes during containment. In current practice the FMA channels are made of heavy seamless copper have rectangular cross-sections and are cooled internally with water. Channels are set at grazing angles ranging from 1 to 6 degrees with respect to the beam depending on the type of insertion device. APS insertion devices will impose higher heat fluxes on FMAs. Therefore a need exists to improve the FMA engineering keeping in mind the current design criteria and philosophy of FMAs. A comparative investigation of the conventionally achievable heat transfer coefficient h" with water and the wall conductance of a heavy wall copper tube reveals that major resistance is on the coolant side. Therefore there exists a significant opportunity to improve heat transfer in the tubes by enhancement of the coolant side. To this end an experimentally and analytically based research program has been adopted at the APS for investigating enhanced cooling methods and techniques. Currently a variety of copper wool filled tubes as well as a© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Naloxone inhibits immune cell function by suppressing superoxide production through a direct interaction with gp91phox subunit of NADPH oxidase

Background Both (-) and (+)-naloxone attenuate inflammation-mediated neurodegeneration by inhibition of microglial activation through superoxide reduction in an opioid receptor-independent manner. Multiple lines of evidence have documented a pivotal role of overactivated NADPH oxidase (NOX2) in inflammation-mediated neurodegeneration. We hypothesized that NOX2 might be a novel action site of naloxone to mediate its anti-inflammatory actions.
Heat Transfer Augmentation Through Wall-Shape-Induced Flow Destabilization

Experiments on heat transfer augmentation in a rectangular cross-section water channel are reported. The channel geometry is designed to excite normally damped Tollmein-Schlichting modes in order to enhance mixing. In this experiment, a hydrodynamically fully developed flow encounters a test section where one channel boundary is a series of periodic, saw-tooth, transverse grooves. Free shear layers span the groove openings, separating the main channel flow from the circulating vortices contained within each cavity. The periodicity length of the grooves is equal to one-half of the expected wavelength of the most unstable mode. The remaining channel walls are flat, and the channel has an aspect ratio of 10:1. Experiments are performed over the Reynolds number range of 300 to 15,000. Streakline flow visualization shows that the flow is steady at the entrance, but becomes oscillatory downstream of an onset location. This location moves upstream with increasing Reynolds numbers. Initially formed traveling waves are two dimensional with a wavelength equal to the predicted most unstable Tollmien-Schlichting mode. Waves become three dimensional with increasing Reynolds number and distance from onset. Some evidence of wave motion persists into the turbulent flow regime. Heat transfer measurements along the smooth channel boundary opposite the grooved wallmore » show augmentation (65%) over the equivalent flat channel in the Reynolds number range 1,200 to 4,800. The degree of enhancement obtained is shown to depend on the channel Reynolds number, and increases with the distance from the onset location.« less
Ethics in Psychiatric Research: A Review of 25 Years of NIH-funded Empirical Research Projects

Background: This paper reviews the past 25 years of empirical research funded by the National Institutes of Health (NIH) on matters of ethics in psychiatric research. Methods: Using the NIH RePORTER and Medline databases, we identified 43 grants and 77 publications that involved the empirical study of a matter of ethics in research involving mental health service users. Results: These articles provide original and useful information on important topics, most especially the capacity to consent and the voluntariness of consent. For example, participants who share a diagnosis vary widely in levels of cognitive impairment that correlate with decisional capacity, and capacity to consent can be enhanced easily using iterative consent processes. Few articles address matters of justice or benefits in research, particularly from the perspectives of participants. No articles address matters of privacy, confidentiality, or researcher professionalism. Conclusions: Despite the usefulness of data from the studies condu...