cssi/SciSciGPT-SciSciNet huggingface dataset:
Undiscovering the Pueblo Mágico: Lessons from Huautla for the Psychedelic Renaissance

The people of the Sierra Mazateca region of Mexico became internationally known in the 1950s for their ritual use of psilocybin mushrooms, and the Mazatec town of Huautla became a destination for mushroom seeking visitors. This chapter provides an overview of changing Mazatec and “outsider” discourses about mushrooms and the Sierra Mazateca over the last 60 years. It argues that “outsider” representations of the Sierra Mazateca and mushroom use—whether framed in terms of spiritual journeys or scientific research—tend to recapitulate some consistent patterns common to other forms of cultural tourism that owe more to the role of substances in marking distinctive cultural identities than to the effects of the substances themselves. It concludes by suggesting lessons from this history for the current moment, in which a discourse framing the use of psychedelic substances through universalizing narratives of science and individual health is becoming ascendant
Original Works of Freud on Women: Social Work References:

Freud's views on women were widely accepted by the social work profession from the 1920s until recently. A review of the literature shows how Freudian theory was disseminated into social work and w...
Belief consistency and invariant risk preferences

Abstract Karni and Viero (2013) introduce a novel theory characterizing the evolution of decision makers’ beliefs in response to growing awareness of new conceivable contingencies. As awareness grows, the original subjective expected utility (SEU) preferences need to be reformulated. Under two key axioms linking the original and new preferences, Invariant Risk Preferences and Consistency, the authors derive representation theorems and updating rules for beliefs referred to as reverse Bayesianism. We prove that their Consistency axiom together with the SEU axioms implies Invariant Risk Preferences. In other words, we show that the theory of reverse Bayesianism can be behaviorally underpinned without directly imposing Invariant Risk Preferences.
Crystallographic Evidence for a Sterically Induced Ferryl Tilt in a Non‑Heme Oxoiron(IV) Complex that Makes it a Better Oxidant

Oxoiron(IV) units are often implicated as intermediates in the catalytic cycles of non-heme iron oxygenases and oxidases. The most reactive synthetic analogues of these intermediates are supported by tetradentate tripodal ligands with N-methylbenzimidazole or quinoline donors, but their instability precludes structural characterization. Herein we report crystal structures of two [FeIV (O)(L)]2+ complexes supported by pentadentate ligands incorporating these heterocycles, which show longer average Fe-N distances than the complex with only pyridine donors. These longer distances correlate linearly with log k2 ' values for O- and H-atom transfer rates, suggesting that weakening the ligand field increases the electrophilicity of the Fe=O center. The sterically bulkier quinoline donors are also found to tilt the Fe=O unit away from a linear N-Fe=O arrangement by 10°.
Asymptotic Analysis of Multilump Solutions of the Kadomtsev–Petviashvili-I Equation

We construct lump solutions of the Kadomtsev–Petviashvili-I equation using Grammian determinants in the spirit of the works by Ohta and Yang. We show that the peak locations depend on the real roots of the Wronskian of the orthogonal polynomials for the asymptotic behaviors in some particular cases. We also prove that if the time goes to −∞, then all the peak locations are on a vertical line, while if the time goes to ∞, then they are all on a horizontal line, i.e., a π/2 rotation is observed after interaction.
‘We’re more ethical than they are’: Third-person and first-person perceptions of the ethical climate of American journalists:

This study advances our understanding of mainstream US journalists’ perceptions of their industry’s ethical climate by extending first- and third-person perception to this domain. These journalists...
Renal Developmental Anomalies

The kidney has a complex origin and some familiarity with its development assists in understanding the numerous congenital disorders of the kidney. Two structures, the ureteric bud and the metanephric blastema, must develop and interact in a normal fashion to produce a normal kidney. The earliest precursor to the adult kidney appears at the end of the third gestational week, when a transient cellular condensation forms the pronephros. This tissue is nonfunctional and soon involutes.
TCT-108 Long-term Survival After Hybrid Coronary Revascularization for Triple-Vessel Disease: How Does it Compare to Coronary Artery Bypass Surgery or Multi-Vessel Percutaneous Intervention?

Hybrid coronary revascularization (HCR) combines a left internal mammary artery (LIMA) to left anterior descending (LAD) surgical graft, usually performed via a robotic-assisted, minimally-invasive approach, with drug-eluting stents placed in the remaining diseased non-LAD vessels. We sought to
New Trends in Second Language Learning and Teaching through the lens of ICT, Networked Learning, and Artificial Intelligence

In the last few decades, Information and Communications Technology (ICT) applications have been shaping the field of Computer Assisted Language Learning (CALL). Mobile Assisted Language Learning (MALL) paved the way for ubiquitous learning. The advent of new technologies in the early 21st century also added a social dimension to ICT that allowed for Networked Learning (NL). Given that language learning is fundamentally a socio-cultural experience, networked learning capabilities have provided the potential for language learning in community settings. This has revitalized the earlier frameworks provided by CALL. NL has empowered language learners today to connect globally, to access Open Educational Resources, and to self-regulate their learning processes beyond the scope of traditional curricula. In parallel, the rising pervasiveness of Artificial Intelligence (AI) applications and their relevance to language learning has led CALL to branch out into Intelligent CALL (ICALL). The first section of this article provides a brief historical overview of CALL, examines it through the lens of ICT, networked learning, and open access. The second section focuses on the implications of AI for creating new trends in second language education, the challenge for providing customization at scale, and raises important issues related to transparency and privacy for future research.
Comparison of transverse and longitudinal real-time ultrasound scans for prediction of lean cut yields and fat-free lean content in live pigs

Live animal real-time ultrasound scans and carcass measures were taken on 80 pigs comprising two sexes (42 barrows; 38 gilts) and two halothane genotypes (40 carriers and 40 negatives) that were slaughtered between 108 and 148 kg live weight. Transverse scans (TRUS), at right angles to the midline, were taken on right (RS) and left (LS) sides at the last rib. Longitudinal scans (LON) were taken 6.5 cm off the midline immediately anterior (ANT) and posterior (PST) to the last rib on both the RS and LS. Longissimus muscle depth and area and backfat thickness over the longissimus muscle were measured on TRUS. Backfat thickness and longissimus muscle depth were measured at each end of the LON. Backfat thickness and longissimus muscle measurements were taken at the 10th and last rib on the RS of the carcass. Carcasses were fabricated using standard techniques to establish lean cut yields and carcass soft tissue was chemically analyzed to determine fat-free lean contents. Stepwise regression analysis was performed to develop equations to predict the weights and percentages of lean cuts and fat-free lean. Fat and muscle measures taken from ultrasound scans were generally less accurate than last rib carcass measures at predicting composition. There was little difference in R2 for equations based on either TRUS or ANT/LON; however, PST/LON, generally, were less accurate than ANT/LON. Combining measurements from more than one scan gave little improvement in R2 compared with the best single scan. Estimates of sex bias for carcass composition prediction were small. Halothane genotype and carcass lean content biases were detected; equations derived from the pooled data tended to overestimate the lean content of negative pigs and fatter carcasses and underestimate the lean content of carrier animals and leaner carcasses.
Repairs of the Ear

The external ear, or auricle, is a complex three-dimensional structure with an intricate topography that presents unique reconstructive challenges. Consideration of the anatomic, functional, and cosmetic requirements of the auricle facilitates effective surgical reconstruction. Repairs of the ear can be divided into four major categories that address these requirements in different ways: linear and wedge repairs, skin grafts, single-staged flaps, and multi-staged flaps. There is strong evidence to support the efficacy and safety of auricular reconstruction, and specific categories of repair are optimally suited to particular types of defects. However, with few exceptions, there is a paucity of high-level evidence that directly compares the outcomes of one repair type to another. This chapter provides an evidence-based review of each of the major categories of auricular reconstruction. As an alternative to reconstruction, healing by second intention can be a viable option for surgical defects of the ear, and long-term functional and cosmetic outcomes may be comparable to primary repair for appropriately selected defects.
A View of Managership and Leadership from 30,000 Feet: An Historical Perspective

To the extent that there is considerable ambiguity and overlap when it comes to defining the managership and leadership constructs and their components, progress in advancing the field has appreciably slowed; but the frustration of scholars and practitioners is not abated. Hence, what is needed is a good faith effort to take a look at these constructs from 30,000 feet in order to get a better view of the ambiguities and overlaps which are harder to detect from the ground level. Such an effort invariably requires an historical perspective. Precise definitions of management and leadership constructs are necessary so that researchers possess adequate constructs required for formulating testable hypotheses. Moreover, international and American scholars need to be on the same page. Until that is accomplished, progress in advancing the field will continue to be stymied. Toward that end, this effort attempts to identify the ambiguities and overlaps and proposes tentative solutions.
Performance of an IS Scheme Based on a Subsolution

In Chap. 14 we considered the problem of rare event simulation associated with small noise discrete time Markov processes of the form analyzed in Chap. 4. Two types of events were emphasized: those that are described by process behavior on a bounded time interval (finite-time problems) and those that concern properties of the process over unbounded time horizons (e.g., exit probability problems).
Building and exploring libraries of atomic defects in graphene: Scanning transmission electron and scanning tunneling microscopy study.

The presence and configurations of defects are primary components determining materials functionality. Their population and distribution are often nonergodic and dependent on synthesis history, and therefore rarely amenable to direct theoretical prediction. Here, dynamic electron beam–induced transformations in Si deposited on a graphene monolayer are used to create libraries of possible Si and carbon vacancy defects. Deep learning networks are developed for automated image analysis and recognition of the defects, creating a library of (meta) stable defect configurations. Density functional theory is used to estimate atomically resolved scanning tunneling microscopy (STM) signatures of the classified defects from the created library, allowing identification of several defect types across imaging platforms. This approach allows automatic creation of defect libraries in solids, exploring the metastable configurations always present in real materials, and correlative studies with other atomically resolved techniques, providing comprehensive insight into defect functionalities.
Weaving child psychoanalysis: Past, present, and future

Using the metaphor of a fabric woven from many threads, this paper describes nine of the many conceptual strands that have contributed to the development of child psychoanalysis over its first century. It notes the unfortunate isolation (sometimes self-imposed) of child analysis from related fields (including adult analysis) and argues that we must recognize both the strengths and weaknesses of our psychoanalytic tools if we are to collaborate with and profit from the work of nonanalytic colleagues. It closes with the suggestion that the continued weaving of child analysis will require the creation of new looms, structures that are able to support a new generation of child analysts and the continued elaboration of the field.
Mouse higher visual areas provide both distributed and discrete contributions to visually guided behaviors

Cortical parallel processing streams segregate many diverse features of a sensory scene. However, some features are distributed across streams, begging the question of whether and how such distributed representations contribute to perception. We determined the necessity of primary visual cortex (V1) and three key higher visual areas (LM, AL and PM) for perception of orientation and contrast, two features that are robustly encoded across all four areas. Suppressing V1, LM or AL decreased sensitivity for both orientation discrimination and contrast detection, consistent with a role for these areas in sensory perception. In comparison, suppressing PM selectively increased false alarm rates during contrast detection, without any effect on orientation discrimination. This effect was not retinotopically-specific, suggesting a distinct role for PM in the regulation of noise during decision-making. Thus, we find that distributed representations in the visual system can nonetheless support specialized perceptual roles for higher visual cortical areas.
Methylome and Complete Genome Sequence of Parageobacillus toebii DSM 14590T, a Thermophilic Bacterium.

ABSTRACT Here, we present the first complete genome assembly of the thermophilic bacterium Parageobacillus toebii DSM 14590T. The P. toebii DSM 14590T genome consists of a 3,270,071-bp circular chromosome and a 52,989-bp native plasmid.
How Walkable Neighborhoods Promote Physical Activity: Policy Implications for Development and Renewal:

Mitigating physical inactivity is vital for public health. Neighborhoods that include visually engaging, eye-catching objects and locations increase the frequency, duration, and vigorousness of res...
A feedback loop governs the relationship between lipid metabolism and longevity

The relationship between lipid metabolism and longevity remains unclear. Although fat oxidation is essential for weight loss, whether it remains beneficial when sustained for long periods, and the extent to which it may attenuate or augment lifespan remain important unanswered questions. Here, we develop an experimental handle in the Caenorhabditis elegans model system, in which we uncover the mechanisms that connect long-term fat oxidation with longevity. We find that sustained β-oxidation via activation of the conserved triglyceride lipase ATGL-1, triggers a feedback transcriptional loop that involves the mito-nuclear transcription factor ATFS-1, and a previously unknown and highly conserved repressor of ATGL-1 called HLH-11/AP4. This feedback loop orchestrates the dual control of fat oxidation and lifespan, and shields the organism from life-shortening mitochondrial stress in the face of continuous fat oxidation. Thus, we uncover one mechanism by which fat oxidation can be sustained for long periods without deleterious effects on longevity.
Square salads: exploring the diet of the southern hairy-nosed wombat (Lasiorhinus latifrons) via DNA metabarcoding

Southern hairy-nosed wombats (Lasiorhinus latifrons) are large semi-fossorial marsupials that inhabit semiarid areas of southern South Australia and southeast Western Australia. Despite their size and prominence on the landscape, little is published about diet and foraging preferences. Further, it is unclear whether this wombat species’ diet overlaps with sympatric western grey kangaroos (Macropus fuliginosus), which are locally abundant across the southern hairy-nosed wombat’s distribution. Competition for food resources may be an added stressor in Murraylands populations where kangaroos are plentiful. Here, we identified diet items and dietary overlap of southern hairy-nosed wombats and western grey kangaroos. We accomplished this by opportunistically sampling fresh faecal pellets from both species at Brookfield Conservation Park in April 2017. We performed DNA metabarcoding via Illumina next generation sequencing of the faecal DNA using the plant ITS2 gene. We identified 10 genera in the wombat diet and 20 in the diet of kangaroos; diets of both species included native and introduced genera. Eight genera were shared between both marsupials. This work highlights the capabilities of non-invasive genetic sampling in concert with DNA metabarcoding to elucidate diet and dietary overlap between species.
The Convergent Validity of the PEAK-E-PA and Two Common Assessments of Language Development: The ABLLS-R and the TOLD 1:4

The study evaluated the convergent validity of the PEAK-E-PA and two common assessments of language development used in educational and clinical settings: the ABLLS-R and the TOLD-I:4. The PEAK-E-PA provides a measure of a participant’s ability to derive arbitrary stimulus relations, and may therefore provide a more complex analysis of language functioning than traditional behavior analytic language assessments. The results of the present study support a strong, significant relationship between the PEAK-E-PA and the ABLLS-R (r = 0.73, p < 0.01), but the obtained coefficient falls within the lower range of prior psychometric evaluations of behavioral language assessments. The results suggest a stronger relationship between the PEAK-E-PA the TOLD-I:4 (r = 0.94, p < 0.01), supporting the use of the PEAK-E-PA with individuals with autism who have progressed beyond the elementary verbal operant skills assessed for in traditional behavioral assessments.
Accuracy of Patient Height, Weight and Ideal Body Weight Estimates in the Emergency Department.

# CONTEXT The purpose of this study was to establish the accuracy of emergency medicine professionals’ estimates of a sample of patients’ heights, weights and ideal body weights (IBW). # METHODS This was a cross-sectional survey study with 69 emergency medicine professionals concerning estimates of five standardized patients. Board-certified emergency physicians, emergency medicine residents and emergency department nurses were asked to estimate patient height, weight and (IBW) by looking at a series of photographs of five standardized patients with varied body types. Repeated measure analysis of variance procedures were used to examine for estimates-to-actual measurement differences. # RESULTS Overall height, weight and IBW estimate differences did vary significantly for the majority of the five standardized patients. Respondents’ clinical position (i.e., attending physician, resident, or nurse) and years of clinical experience did show a significant level of influence on estimate-to-actual differences for some proportion of patient estimates. # CONCLUSION Our results support the common belief that the accuracy of overall weight and height estimates in emergency department settings is unacceptably low, and that a patient's stated weight and height is likely to be more accurate. Further work is required in this area of emergency medicine practice since these types of inaccuracies could potentially compromise the effectiveness of therapies and treatments during emergent situations.
A reconstruction error-based framework for label noise detection

Label noise is an important data quality issue that negatively impacts machine learning algorithms. For example, label noise has been shown to increase the number of instances required to train effective predictive models. It has also been shown to increase model complexity and decrease model interpretability. In addition, label noise can cause the classification results of a learner to be poor. In this paper, we detect label noise with three unsupervised learners, namely $$\textit{principal component analysis} \hbox { (PCA)}$$ , $$\textit{independent component analysis} \hbox { (ICA)}$$ , and autoencoders. We evaluate these three learners on a credit card fraud dataset using multiple noise levels, and then compare results to the traditional Tomek links noise filter. Our binary classification approach, which considers label noise instances as anomalies, uniquely uses reconstruction errors for noisy data in order to identify and filter label noise. For detecting noisy instances, we discovered that the autoencoder algorithm was the top performer (highest recall score of 0.90), while Tomek links performed the worst (highest recall score of 0.62).
The kinetics of ligand binding to hemoglobin valency hybrids and the effect of anions.

Abstract The time course of carbon monoxide binding to stripped valency hybrids (αiiβiiiCN)2 and (αiiiCNβii)2 was studied at pH 6.6 and T = 0.05. It exhibits a strong heterogeneous character. Two spectrophotometrically and kinetically distinct forms are apparent. At most wave lengths the fast component contributes about 60 to 80% of the total absorbance change and has a rate of binding similar to that of rapid hemoglobins. Correlation between the spectral properties of hybrids and their fast reacting character is demonstrated. These results are consistent with a scheme where deoxy hybrids exist in solution as two different configurations (R and T) not in rapid equilibrium. There is evidence that the rapidly reacting deoxy hybrids are in a form different from that of the R form of liganded hemoglobin. Upon addition of organic phosphates, 2,3-diphosphoglycerate and inositol hexaphosphate, the fast component becomes slowly reacting and the slow component is little affected. Qualitative analyses of the progressive effect of 2,3-diphosphoglycerate on the kinetics of hybrids are in accord with the suggested scheme. Titration of hybrids with the fluorescent analog of organic phosphates (8-hydroxy-1,3,6-pyrenetrisulfonate) shows that 1 mole of anion is bound by hybrid tetramer, and that (αiiiCNβii)2 has the greater affinity toward anions. Some kinetics of hybrids with other ligands (oxygen, azide, and n-butyl isocyanide) have been studied. The reactions are homogeneous and proceed faster when the β chain of the hybrids is free to react, except in the case of carbon monoxide, where the α chains react more rapidly.
Approaches to the Development of Cosmetic Products to Counter the Effects of Skin Aging

Publisher Summary This chapter focuses mainly on the treatments for face, as facial beauty and appearance are the most significant and recognizable yardstick of youth and aging in human societies. Antiaging cosmetic products are being developed with the most sophisticated cell and molecular biology techniques, including gene arrays, SAGE, and proteomics in scientific laboratories the world over, using isolated skin cells to pinpoint the beneficial effects of active ingredients. Such studies are followed by testing on three-dimensional skin equivalents, which alleviates the need for animal testing. An array of noninvasive techniques utilizing instrumentation to measure a wide array of skin responses, parameters, and physiological functions has aided the cosmetic scientist and the dermatologist in quantifying the biological effects for claim substantiation of antiaging products. True antiaging efforts should have a holistic approach, addressing not only skin care, but nutrition, wellness, balanced lifestyle, and stress management. The cosmetic industry is embracing such an approach, and with increasing consumer awareness industry investments in research and development efforts to meet this need, antiaging is no more just a buzzword.
Exchange Systems in Prehistory

Thirty years ago today (and then some), Exchange Systems in Prehistory (Earle and Ericson 1977) was published. The editors of the present volume offered me the chance to consider how exchange studies have grown over the last generation and what major challenges lie ahead. My plan is to summarize briefly the state of the field in the 1970s and then trace briefly major forward movements leading to this first decade of the twenty-first century. Rather than review the countless studies and stream of useful books and articles on the topic, I offer thoughts on where we have come from and where we must go (Earle 1994, 1999). We have solved many analytical problems with source identification and have learned to view exchange as a means to form and maintain social and power relationships, but challenges remain ahead. We are just beginning to model the complex and conflicting ways in which elites and commoners in opposition and in collaboration used exchange in their daily lives and on special occasions. The present volume points directions in our path toward a more integrated view of economy and society.
Rentier States and State Transformations

This chapter reviews the large and influential literature investigating the causal relationship between resource abundance and predatory state institutions, autocratic politics, and civil war. It emphasizes the diversity of findings and identifies an orthodox position positing an unmediated effect of resource abundance; a heterodox position contending that the relationship is mediated by important variables; and a heretical position that denies any systematic relationship between resource abundance and political-economic outcomes. The chapter then considers three key challenges to the main claim positing a relationship: problems of measurement, problems of properly specifying the relevant counterfactual, and problems of identifying causal mechanisms. It concludes that state institutions are largely exogenous to resource abundance and that theories of resource abundance should be incorporated into broader and more encompassing theories of state formation and its consequences.
Endowment Growth and Decline at Private Colleges, 1999-2009

Against the background of the debate over appropriate endowment spending rates for colleges, it is of interest to examine exactly what has happened to private colleges’ endowment market values over the decade from 1999 to 2009. In the aggregate, where do private college endowments stand in 2009 relative to 1999? How does the picture change as one moves from a perspective based on nominal values to a perspective based on real, inflation-corrected values? How do the results differ across colleges? Does growth vary in a way that is systematically linked to starting endowment size as of 1999? To the extent that growth varies, how much of the variation is attributable to differences in endowment investment returns and how much is attributable to other factors?Given the dismal investment returns of 2009, it is not surprising that the decade from 1999 to 2009 was one of dismal results for private colleges’ endowment market values. Yet, the path to this characterization of market values is more complex than a brief reference to 2009’s investment returns.For the 221 private colleges included in this paper, a first step on that path is that, in the aggregate, their nominal endowment market value increased by 55.6% from 1999 to 2009. While the 55.6% may initially appear to constitute a healthy increase, such a characterization is undermined by several considerations.First, the aggregate endowment market value is driven by the strong growth at the colleges with the largest starting (as of 1999) endowments. The “rich did get richer” relative to the less rich, and the median percentage increase in nominal endowment market value at the 221 private colleges from 1999 to 2009 was 21.9%.Second, the median change in real, inflation-corrected endowment market values for the 221 colleges was -18.2%.Third, a common perspective is that the purchasing power of existing endowment should be sustained over time without the benefit of new gifts. Including the impact of such new gifts, real endowment market value should increase over the course of a decade. Adjusting for a conservative assumption of a new gift rate of 2.0% of annual starting endowment market value, the estimate (assuming also that the purchasing power of the new gifts is sustained) is that real endowment market value should grow by approximately 21.0% over a decade. The actual median real change of -18.2% stands sharply below this 21.0%.
Improved logic optimization using global flow analysis

Techniques for automatically reducing circuit size and improving testability are considered. Two extensions to a previously published method for circuit optimization based on ideas of global flow analysis are described. The first is a basic improvement in the primary results on which the earlier optimization was based; the second extends the applicability of the method to conditional optimizations as well. Together these enhancements result in improved performance for the original algorithm, as well as the ability to handle designer-specified don't cares and redundancy-removal uniformly in the framework of a graph-based synthesis system such as LSS. >
The biochemistry of skin disease: psoriasis.

Publisher Summary This chapter reviews the biochemistry of skin disease, which is of interest to a clinical chemist. Psoriasis is the only skin disease, which has been extensively studied and whose clinical, biochemical, and physiological aspects are unfamiliar to most scientists outside dermatology. Although there are no biochemical tests, which can yet be performed in the laboratory to help confirm the diagnosis or to aid in the prognosis or choice of therapy, the biochemical enigmas encountered in the study of this disease are of interest to all biologists. Psoriasis is common, it has a definite genetic background, has uncontrolled yet not malignant growth as its outstanding feature, has disordered maturation and differentiation, has an experimental model in the Koebner reaction, and it has intense metabolic and mitotic activity. It also has material readily available for study and it offers the possibility of helping millions of people who suffer but usually do not die.
Automatic generation of microarchitecture simulators

We describe the UPFAST system that automatically generates a cycle level simulator, an assembler and a disassembler from a microarchitecture specification written in a domain specific language called the Architecture Description Language (ADL). Using the UPFAST system, it is easy to retarget a simulator for an existing architecture to a modified architecture since one has to simply modify the input specification and the new simulator is generated automatically. UPFAST also allows porting of simulators to different platforms with minimal effort. We have been able to develop three simulators ranging from simple pipelined processors to complicated out-of-order issue processors over a short period of three months. While the specifications of the architectures varied from 5000 to 6000 lines of ADL code, the sizes of automatically generated software varied from 20000 to 300000 lines of C++ code. The automatically generated simulators are less than 2 times slower than hand coded simulators for similar architectures.
Psychiatric Side Effects of Interferon Therapy: Prevalence, Proposed Mechanisms, and Future Directions

ABSTRACT: The increasing use of interferon (IFN) in treating a variety of disorders including, malignant melanoma and hepatitis C, has resulted in the identification and increasing concern about the psychiatric side effects that can result from treatment. These effects can occur either shortly after beginning IFN therapy or later as a result of continued treatment. Studies have reported the incidence of later side effects, which include symptoms of depression, anxiety, and occasional suicidal ideation, to be from 0% to 70%. Case studies have demonstrated that pharmacologic interventions are beneficial in reducing iatrogenic psychiatric symptoms while allowing patients to maintain IFN therapy. The present article provides an overview of the psychiatric effects of IFN therapy, the proposed mechanisms of these side effects, and case studies that provide mechanistic support. In addition, limitations of the current literature are provided with suggestions for treating physicians and a discussion of possible fu...
Targeting cells in motion: Migrating toward improved therapies

The development of clinical therapeutics that interfere with the migration of leukocytes has revolutionized the treatment of multiple sclerosis and holds great promise for the treatment of a wide range of inflammatory diseases. As the molecules essential for the multi-step adhesion cascade that mediates cellular migration have been elucidated, the number of potential targets available to modulate leukocyte trafficking has increased exponentially. In this Viewpoint, we briefly review our current understanding of these mole-cular targets and how these targets vary by tissue and leukocyte subset with emphasis on T cells. We then describe the two currently approved therapeutics that target cell migration, natalizumab and fingolimod, and discuss how an improved understanding of their function could pave the way for the development of safer and more efficacious therapies for inflammatory and autoimmune diseases.
Perseverations in Alzheimer's disease: Memory slips?

Previous studies of verbal fluency tasks reported higher rates of repeated responses in Alzheimer's disease (AD) compared to elderly controls. The present investigation aimed at determining if perseverations are caused by word retrieval deficits or working memory deficits, both of which are commonly observed in AD. Based on current theories of lexical processing and working memory, we derived specific predictions concerning the lag between the first occurrence of a word and its repetition. With word retrieval deficits, repetitions are expected to be progressively less frequent at greater lags; conversely, with working memory deficits, repetitions should occur especially after long lags. These predictions were tested analyzing the performance of 392 AD individuals in verbal fluency tasks. The finding of lags that were significantly longer than would be expected by chance is consistent with the hypothesis that perseverations are primarily caused by working memory deficits. Specifically, we propose that perseverations stem from an impairment affecting the working memory mechanisms that control response monitoring. We also investigated the relationship between perseverations and other cognitive deficits observed in AD. We discuss the implications of our findings for understanding the nature of perseverations, the effects of working memory deficits in AD, and the neural correlates of working memory components.
Complete Endocardial Cushion Defect: The Late Result of Repair Using the Single-Patch Technique

Twenty-two patients have been followed for between 1 and 105 months after repair of a complete endocardial cushion defect. The mean period of follow-up is 3.5 years. The single-patch technique was used in every patient. The mitral valve was repaired with buttressed sutures in those seen more recently. The mean age at the time of operation was 15 months. Early in this experience, 4 patients had severe mitral valve incompetence after an initially satisfactory repair. In none of those patients had the mitral valve been repaired with pledgeted sutures. Two of those patients survived reoperation, and 2 died before a second operation could be performed. Every mitral valve is now repaired with pledgeted sutures, and there have been no failures of the mitral valve reconstruction. Each patient has been followed by the same pediatric cardiologist every 6 to 12 months after operation. The vast majority (17 of 20) are asymptomatic. Twelve have no mitral valve incompetence, and the remainder have only trivial or mild incompetence. Clinically, the pulmonary artery hypertension has resolved in 19 of 20 patients. Each patient remains in normal sinus rhythm. The long-term results following repair of complete endocardial cushion defect with the single-patch technique are excellent, but pledgeted sutures should be used in the mitral valve repair to insure its integrity.
The second law of thermodynamics and quantum heat engines: Is the law strictly enforced?

Abstract A quantum heat engine is a construct having a working medium which is cyclically processed through a pair of control variables of state involving a Bose–Einstein condensation (BEC) in which a heat input is converted into a work output. Of interest is a first species of quantum heat engine in which the working medium is macroscopic in the sense the size scale is sufficiently large that the BEC is not volumetrically coherent. In this first species of quantum heat engine, near Carnot efficiencies may be possible. Of particular interest is a second species of quantum heat engine in which the working medium is mesoscopic in the sense that the size scale is sufficiently small that the BEC is volumetrically coherent. In this second species of quantum heat engine, the resulting in-process non-equilibrium condition affects the finally arrived at control variables of state such that Carnot efficiencies and beyond may be possible. A Type I superconductor is used to model the first and second species of quantum heat engine.
Simple Method for Visualization of the Islets in Fixed But Otherwise Intact Pancreas

A simple, inexpensive, reproducible method is described for prominently displaying the islets of Langerhans. The method consists of sequential arterial perfusion of the organ of the sacrificed animal with saline, formalin, hematoxylin, and water, followed by clearing in methyl salicylate. The procedure should be useful whenever islet tissue needs to be quantitatively distinguished from nonislet tissue and fixation is allowable.
Long-Lasting Attenuation of Amygdala-Kindled Seizures after Convection-Enhanced Delivery of Botulinum Neurotoxins A and B into the Amygdala in Rats

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula–stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convection-enhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64-day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally, maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.
Equation-of-state calculations of chemical reaction equilibrium in nonideal systems

In order to calculate accurately chemical-reaction equilibria of a system over a wide range of temperatures and pressures, one must account for the non-idealities of the system. In this work, a method is developed to predict accurately chemical-reaction equilibria and phase equilibria of a system using an equation of state to account for the nonidealities. The general formalism for a multicomponent system with multiple reactions is presented. Three widely used cubic equations of state are used to calculate the physical properties of the species. The proposed method is applied to the water-gas shift reaction, to the decomposition of methylcyclohexane, and to the reaction of carbon monoxide with hydrogen sulfide over a wide range of temperatures and pressures.
Coxsackievirus B3: primary structure of the 5' non-coding and capsid protein-coding regions of the genome.

Abstract The nucleotide sequence from the 5′ terminus to nucleotide 3822 has been determined for the genome of the enterovirus, coxsackievirus B3 (CB3). This region encompasses the 5′-terminal 738 nucleotide non-coding sequence and the region which codes for the four viral capsid proteins and for the initial products of the P2 region. Regions in the 5′ non-translated RNA sequence which may be involved with a structural and/or regulatory role are discussed.
American (U.S.) activities in marine mineral deposits

Research efforts in marine mineral deposits in the United States (U.S.) are spread among different agencies, and focused on resource assessment, exploration and discovery, and understanding seafloor hydrothermal systems and related processes. Significant efforts have been made to explore and discover new sites of hydrothermal activity on slow and ultraslow spreading ridges, associated with volcanic arcs, and in back-arc basins, and to develop new platforms, vehicles, and tools for carrying out this exploration. The focus of these programs is on understanding the effects of hydrothermal venting on the global ocean, including deep-sea eco-systems, and on the search for and study of the chemical and microbiological systems at deep-sea vents. The most significant source of funding for research relevant to marine mineral deposits is the National Science Foundation (NSF), with an emphasis on understanding hydrothermal circulation and all of its ramifications, including to ocean crust composition, seawater composition, mineral deposit formation, and biological productivity in the deep-sea. Significant efforts have been made by the NSF Ridge 2000 Program to link heat and mass transfer from the mantle through the crust to the biosphere, through comprehensive study of three very different ridge systems. In addition, NSF has continued to fund investigations of hydrothermal systems and associated deposits and biological communities in a wide range of settings, including in back-arc basins, and on slow-spreading mid-ocean ridges.
Cytochrome b5Is Essential for Cytochrome P450 6D1-Mediated Cypermethrin Resistance in LPR House Flies

Abstract Cytochrome P450 monooxygenase-mediated detoxification is a very important mechanism of resistance to insecticides. In the LPR strain of house fly, the major mechanism of resistance to pyrethroids is monooxygenase-mediated metabolism due to the overexpression of cytochrome P450 6D1 (CYP6D1). Although the role of CYP6D1 in pyrethroid resistance has been demonstrated, there is no information as to whether cytochrome b 5 is involved in this reaction and what the major CYP6D1-specific metabolite is. Using a cytochrome b 5 antiserum we demonstrate that cytochrome b 5 is required for the elevated level of CYP6D1-mediated cypermethrin metabolism observed in microsomes from the resistant LPR strain compared to a susceptible strain. Therefore, cytochrome b 5 is directly involved in this monooxygenase-mediated resistance. NADH has no significant effect on this metabolism, suggesting that in vitro the second electron source for CYP6D1 is NADPH when cypermethrin is the substrate. Using GC-MS, the primary CYP6D1 specific metabolite formed in vitro was identified as 4′-OH cypermethrin.
In vivo comparison of electromagnetic and Doppler flowmeters: with special attention to the processing of the analogue Doppler flow signal

In acute experiments, instantaneous arterial flow tracings were obtained simultaneously with an electromagnetic (square-wave and pulsed field) and a non-directional Doppler flowmeter at rest, during reactive hyperaemia and during isoprenaline infusion. A wide band Doppler flow signal was processed with a zero-crossing meter preceded with and without a differentiator. The performance of both high and low threshold zero-crossing meters was also examined. The combination of a differentiator with a high threshold zero-crossing meter gave the best results. In this way, the Doppler flowmeter followed the electromagnetic flowmeter without loss of high frequency information. Since the differentiator weights the amplitude with respect to frequency, the low amplitude high frequency components, which normally are riding on the high amplitude low frequencies, can be counted in the zero-crossing meter. The peak velocity readings in the femoral artery, however, were significantly higher than those calculated from the electromagnetic flowmeter readings, both with the differentiator and the band-pass filter preceding the zero-crossing meter, necessitating in situ calibration when absolute flow values are required. Possible causes of this discrepancy are discussed.
Clomiphene citrate (CC) administration changes cervical mucus permeability in patients undergoing fertility treatments

tional system that simulates the genetics of gamete production and zygote formation to create ‘‘virtual progeny’’ from the DNA sequences of any two people. This process is applied to reproductively pair male and female participants in the ‘‘1000 Genomes Project’’ based on publicly available exome sequences. The output of a single pairing is 1,000 unique virtual progeny genomes. Each digital genome is analyzed for DNA sequence combinations that could cause one or more recessive Mendelian diseases based on clinical annotations and the total expected output of functional gene products from the two copies of each gene. The data are integrated to produce a detailed assessment of reproductive disease risk. RESULTS: Genetic screening of simulated genomes from over 50,000 pairings uncovered reproductive risk far beyond that exposed by carrier screening of individual persons. Based on coding regions interrogated in over 400 genes, all ‘‘donors’’ for the purposes of this investigation were considered healthy reproductive matches for multiple ‘‘clients.’’ CONCLUSION: Virtual progeny analysis can provide a comprehensive approach to the genetic screening of sperm donors in two distinct ways: 1) by incorporating client DNA information as a necessary input into risk analysis and 2) by selectively avoiding sperm donors based on the analysis of recessive genetic disease risk in the virtual offspring of qualified sperm bank donors and clients. Supported by: GenePeeks, Inc.
Timing Electronics and Fast Timing Methods with Scintillation Detectors

Time spectroscopy involves the measurement of the time relationship between two events. This paper reviews time pick-off techniques, practival time-pickoff circuits, and timing with scintillation detectors. A detailed comparison is made between leading-edge timing and constant-fraction timing. Typical timing resolution results are given for 60Co.