cssi/SciSciGPT-SciSciNet huggingface dataset:
Convergent and divergent evolution of regulatory sites in eukaryotic phosphorylases

The activity of many proteins in eukaryotic cells is regulated by reversible covalent phosphorylation1. This regulatory modification is often linked to other allosteric controls within the same protein2, and such overlapping regulatory mechanisms are best characterized for glycogen phosphorylase (EC 2.4.1.1). Phosphorylases from different organisms or cell types exhibit markedly contrasting regulatory features3; this makes the enzyme attractive for studying the evolution of interacting molecular regulatory mechanisms4,5. Extensive biochemical and crystallographic studies of rabbit muscle phosphorylase have led to a characterization of five regulatory regions (phosphorylation, glycogen storage, AMP, glucose and purine sites)6–8. Here we report the complete primary structure of the yeast Saccharomyces cerevisiae glycogen phosphorylase, deduced from the sequence of the cloned gene. Regions that are highly conserved between muscle and yeast enzymes include the active site, the glycogen storage site and possibly the glucose and purine inhibition sites. Partial conservation of the residues involved in AMP-binding suggests a binding site for the yeast enzyme inhibitor, glucose 6-phosphate9,10. Other parts of the AMP site and the intersubunit contacts involved in AMP allostery are disrupted in the yeast enzyme by extreme sequence divergence. The poor alignment of amino termini and lack of homology at phosphorylation sites indicate that regulation by reversible phosphorylation evolved independently in yeast and vertebrate phosphorylases.
An Example of the Secant Method of Iterative Approximation in a Fifteenth-Century Sanskrit Text

Abstract Mathematical approximation by iterative algorithms is well attested in Sanskrit astronomical texts, but its use has not been studied systematically. In his 14th-century supercommentary on Govindasvāmin's commentary on Bhāskara I'sMahābhāskariya, Parameśvara, a student of the renowned Kerala astronomer Mādhava, presents a one-point iterative technique for calculating the Sine of a given angle, as well as a modification of this technique that involves a two-point algorithm essentially identical to the modern secant method. This paper presents a mathematical and historical interpretation of his remarks. L'approximation mathematique par les procedes d'iteration se manifeste frequemment dans les textes sanscrites astronomiques, mais elle n'est pas beaucoup etudiee. Dans son surcommentaire sur le commentaire de Govindasvāmin sur leMahābhāskariyade Bhāskara I, Parameśvara, un eleve de Mādhava, l'astronome renomme de Kerala, donne un calcul iteratif en virgule fixe pour le calcul du Sinus d'un angle donne, aussi bien qu'une modification de cette methode dans laquelle parait une technique virtuellement identique a la forme discrete de la methode de Newton–Raphson. L'article suivant presente une interpretation mathematique et historique de ses remarques. Die mathematische Annaherung bei den Iterationsverfahren ist in den sanskritischen astronomischen Texten gut bezeugt, aber daruber gibt es nicht viele Studien. In seiner Kommentar uber Govindasvāmins Kommentar uber dieMahābhāskariyades ersten Bhāskaras gibt, Parameśvara, ein Student des bekannten keralischen Astronomen Mādhavas, eine Festkommarechnung fur die Berechnung des Sinus eines gegebenen Winkels, wie auch eine Modifikation dieser Technik; diese Modifikation enthalt einen Algorithmus der grundsatzlich der diskreten Newton–Raphsonischen Methode gleichwertig ist. Dieser Artikel stellt eine mathematische und historische Interpretation seiner Bemerkungen dar.
The effect of oxygen concentration on the quantum yields of the dye-sensitized photoinactivation of trypsin, alpha-chymotrypsin and lysozyme.

Le travail decrit l'effet de differentes concentrations en oxygene sur la photoinactivation de la trypsine, de l'α-chymotrypsine et du lysozyme. Comme sensibilisateurs on a utilise le bleu de methylene, l'eosine Y et le FMN. En general, les rendements quantiques de l'inactivation enzymatique ont augmente avec l'augmentation des concentrations en oxygene, et atteint un plateau a des concentrations de 20% environ. Ils ne changerent alors pratiquement plus lorsque les concentrations en oxygene augmenterent jusqu'a 100%.
Impedance measurements in brain tissue of animals using microvolt signals

Abstract A technique is described for measurement of cerebral impedance with signals in the tissues of 1 to 20 μv amplitude, and having a current density of the order of 10 −13 amperes per square micron of electrode surface at 1000 cycles/sec. The system will resolve a 1 per cent shift in resistive impedance, and is limited in sensitivity only by the input noise of the differential amplifier. Using chronically implanted coaxial electrodes in the cat for both EEG and impedance measurements, certain clear and consistent changes in impedance were observed, particularly in the dendritic layer of hippocampal pyramidal cells and in the septum, in response to somatic, olfactory, visual, and auditory stimuli, and to changing physiological states of consciousness, as well as drug-induced changes during barbiturate anesthesia and the effects of hallucinogenic agents. Certain repeatable changes were also observed during hippocampal seizures. Physiological peripheral stimuli all produced a transient decrease in impedance in the hippocampal dendritic layer. Arousal from normal sleep was also followed by a baseline shift towards a lower impedance. Waning of consciousness was accompanied by a return to a higher level. Normal sleep was accompanied by trains of very regular sinusoidal waves in the septum at about 3 cycles/min. During Nembutal anesthesia, there was a marked increase in impedance in hippocampal dendritic layers, and a return to pre-drug levels with recovery of consciousness. A psychotomimetic cyclohexamine drug produced a converse series of changes. Seizures induced in the hippocampus by septal stimulation were accompanied by small rapid perturbations in impedance, and followed by rhythmic impedance changes at about 1 cycle/sec, occurring on a rising impedance baseline. Differences were noted between impedance changes in the initial seizure episodes and those occurring from identical stimulation 10 days later. The possible relationship of these impedance changes to ionic shifts and volume changes between neuronal elements (or both) and glial tissue, and the extracellular space is discussed, with reference to a possible modulating influence by glial tissue on electrotonic phenomena in dendrites.
Evidence for Clostridium perfringens enterotoxin (CPE) inducing a mitogenic and cytokine response in vitro and a cytokine response in vivo.

We investigated some immunogenic properties of Clostridium perfringens enterotoxin (CPE) in vitro using murine J774A macrophages (MΦ) and in vivo using Swiss Webster (SW) mice. CPE was a potent mitogen in vitro, where cell proliferation increased with CPE concentration. CPE was nonmitogenic when MΦ were concurrently incubated with CPE and interferon gamma (IFN-γ). MΦ incubated in the presence of CPE induced the synthesis of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ), but not interleukin-2 (IL-2). In vivo, CPE induced a pro-inflammatory cytokine response with striking production of IFN-γ, IL-1, and IL-6. Regardless of route of CPE entry, serum cytokine levels generally peaked within 1 h of administration and were maintained for 4–8 h. Although CPE engenders an intense immune response during toxicosis, the toxin does not appear to be a superantigen. Death from CPE-induced shock appears to result from various interrelating immunological mechanisms.
The Virtues of Scholarship and the Virtues of Political Action

Many bioethicists are involved in political advocacy groups as well as scholarship, and this has led to controversy. The virtues that enable scholarship to flourish are in tension with those that are vital for effective participation in political advocacy groups. This produces conflicts for bioethicists that are as serious as financial conflicts of interest. These conflicts cannot simply be eliminated, however. Scholars are citizens who have reason to engage in political action in light of their scholarly conclusions, and bioethicists who are political advocates are thoughtful persons who have reason to engage in scholarship. At best, the conflicts can be mitigated.
The endocrine-disrupting compound, nonylphenol, inhibits neurotrophin-dependent neurite outgrowth.

Endocrine-disrupting compounds (EDCs) may interfere with neuronal development due to high levels of accumulation in biological tissue and potentially aberrant steroid signaling. Treatment of dissociated embryonic Xenopus spinal cord neurons with the EDC, nonylphenol (NP), did not alter cell survival or neurite outgrowth but inhibited neurotrophin-induced neurite outgrowth, effects that were recapitulated by treatment with comparable concentrations of 17β-estradiol (E2) and β-estradiol 6-(O-carboxy-methyl)oxime: BSA (E2-BSA), but not a synthetic androgen. Effects of NP were not inhibited by the nuclear estrogen receptor antagonist, ICI 182,780, but were inhibited by the G protein antagonist, pertussis toxin. Nerve growth factor (NGF)-induced neurite outgrowth in Xenopus neurons was shown to require MAPK signaling. NP did not affect TrkA expression, MAPK signaling, or phosphatidylinositol 3′ kinase-Akt-glycogen synthase kinase 3β (PI3K-Akt-GSK3β) signaling in Xenopus. The ability of NP to inhibit NGF-induce...
Variation in the effectiveness of reinforcement and nonreinforcement following prior inhibitory conditioning

Two conditioned-suppression experiments investigated the effects of prior inhibitory training of A alone upon subsequent reinforcement and nonreinforcement of an AX compound. In Experiment 1, the amount of conditioning to X as a result of reinforcement of AX was increased by previous inhibitory treatment of A and decreased by previous excitatory treatment of A. In Experiment 2, nonreinforcement of AX resulted in the conditioning of a small amount of excitation to X if A alone had a history of inhibitory conditioning. The results are related to a general model of Pavlovian conditioning.
Sex Ratios and Distribution of Spawning King Crabs in Alitak Bay, Kodiak Island, Alaska (Decapoda Anomura, Lithodidae)

Die das Kap Alitak (Alaska) umgebenden Flachgewasser reprasentieren im fruhen Mai wichtige Brutgebiete fur alte adulte Paralithodes camtschatica. Junge adulte Tiere waren ebenfalls vorhanden; sie waren aber weiter verbreitet und hatten ihr Brutgeschaft wahrend des April bereits beendet. Mit Ausnahme eines jungen adulten Mannchen wurden nur grose, nichthautende alte Mannchen in Prakopulation angetroffen. Angesichts der erhobenen Befunde scheint die sex ratio von Mannchen zu Weibchen zur Erhaltung einer gesunden Population auszureichen.
Molecular genetic approaches to the study of primate behavior, social organization, and reproduction †

In the past several decades, the development of novel molecular techniques and the advent of noninvasive DNA sampling, coupled with the ease and speed with which molecular analyses can now be performed, have made it possible for primatologists to directly examine the fitness effects of individual behavior and to explore how variation in behavior and social systems influences primate population genetic structure. This review describes the theoretical connections between individual behavior and primate social systems on the one hand and population genetic structure on the other, discusses the kinds of molecular markers typically employed in genetic studies of primates, and summarizes what primatologists have learned from molecular studies over the past few decades about dispersal patterns, mating systems, reproductive strategies, and the influence of kinship on social behavior. Several important conclusions can be drawn from this overview. First, genetic data confirm that, in many species, male dominance rank and fitness are positively related, at least over the short term, though this relationship need not simply be a reflection of male-male contest competition over mates. More importantly, genetic research reveals the significance of female choice in determining male reproductive success, and documents the efficacy of alternative mating tactics among males. Second, genetic data suggest that the presumed importance of kinship in structuring primate social relationships needs to be evaluated further, at least for some taxa such as chimpanzees in which demographic factors may be more important than relatedness. I conclude this paper by offering several suggestions of additional ways in which molecular techniques might be employed in behavioral and ecological studies of primates (e.g., for conducting "molecular censuses" of unhabituated populations, for studying disease and host-parasite interactions, or for tracking seed fate in studies of seed dispersal) and by providing a brief introduction to the burgeoning field of nonhuman primate behavioral genetics.
SOME ROLE PERCEPTIONS OF WIVES OF ALCOHOLICS

In the field of alcoholism and personality there are a n~unber of studies whose focus on "the wife" as a factor in her husband's alcoholism implies that the wives of alcoholics have attitudinal and personality characteristics in common, i.e., are a unitary group. Further, the literature suggests that these similar attitudes and personality characteristics may play a part in the onset and/or resolution of the husband's deviant drinking (Ballard, 1959; Futterman, 1953; Igersheimer, 1959; Kalashian, 1959; Lewis, 1954; Macdonald, 1958; Mitchell, 1959; Price, 1945; Whalen, 1953). There are two separate implications to be considered. If the wife is a factor in her husband's becoming alcoholic, there should be demonstrable differences between wives whose husbands were or are alcoholic and those whose husbands have had no drinking problem. If the wife plays an important role in whether or not her husband's alcoholism is resolved, it is anticipated that wives whose husbands have achieved sobriety successfully would differ from those whose husbands continue to drink. The study reported here derives from a more comprehensive research program, still in progress, which provides for assessment of the wife's role in both onset and resolution of the alcoholism, by examining a control group of comparable families without alcoholism, and by making the comparisons noted above. The present investigation was concerned with examining empirically two questions which have bearing on the wife's role in the resolution of alcoholism. Are there demonstrable differences between the attitudes of wives whose husbands have achieved sobriety successfully and those whose husbands have not? Can the "wives of alcoholics" be considered as a unitary group, having certain characteristic attitudes in common? Forty Ss were drawn from the roster of women who had attended at least one meeting of the Alanon Family Groups in Seattle between 1952 and 1959. Their mean age was 41.4 yr.; range, 25 to 65. Twenty women (the AA Group) had husbands who had remained abstinent for more than 12 consecutive months (range of sobriety 14 mo. to 14 yr., mean 6.5 yr.); 20 women (the A Group) had husbands who were still active alcoholics. Participation in the Alanon program was essentially the same for the A and AA wives.
Stuck in the Middle: The Use and Interpretation of Mid-Points in Items on Questionnaires

Likert-type scales are commonly used when assessing attitudes, personality characteristics, and other psychological variables. This study examined the effect of varying the number of response options on the same set of 28 attitudinal items. Participants answered items using either a 4-point scale (forced choice), a 5-point scale that included a "neither" mid-point, or a 4-point scale with an option of "no opinion" presented after the item. The questionnaire also included an item asking participants what they believe the midpoint in a scale indicated. As predicted, participants' interpretations of the midpoint varied widely with the most common responses being: "no opinion," "don't care," "unsure," "neutral," "equal/both," and "neither." The quantitative results showed that participants' levels of item endorsement varied based on the response options offered. For example, "neither" was chosen more often than "no opinion" on all of the items.
Significance of abnormalities involving chromosomal segment 11q22–25 in acute leukemia

Six hundred and thirty unselected cases of acute leukemia, with complete data regarding age, karyotype (with breakpoints), and the diagnosis according to the FAB classification, were available in the literature and from our unpublished cases for comparing the incidence of chromosomal abnormalities involving the long arm of chromosome #11 among age groups in acute nonlymphocytic leukemia (ANLL) and acute lymphocytic leukemia (ALL). A statistically highly significant difference (p less than 0.001) was observed between the incidence of ANLL cases with chromosome aberrations involving 11q22-25 in childhood (less than or equal to 15 years) versus that in adults (greater than 15 yr). This statistical difference was not only related to infant cases (less than or equal to 12 months), but also to cases of children over 1 year of age. The incidence of the 11q22-25 abnormality in childhood cases (greater than 1 yr to less than or equal to 15 yr) was statistically significant (0.025 less than p less than 0.05) when compared to the incidence in adult cases. The incidence of the 11q22-25 abnormality in infant cases was much higher when compared to that of older cases with either ANLL or ALL (p less than 0.001 in each leukemia). This trend was not observed in cases with the 11q11-21 abnormality and this may imply that the origin and meaning of the 11q11-21 abnormality may differ from that of the 11q22-25 abnormality. Twenty-three infants with acute leukemia (AL) with the 11q22-25 abnormality were available from previous reports and our unpublished case. The median ages of ANLL, ALL, and all AL cases were 16 weeks, 9 weeks, and 15 weeks, respectively. The tendency of the 11q22-25 abnormality to be common in infants with ANLL or ALL under 6 months of age may suggest that it has a close correlation with the origin(s) or mechanism(s) related to the occurrence of infant AL.
Reproducibility of Brachial Artery Ultrasound Measurements.

Recent findings suggest that systemic artery endothelial function is associated with the preclinical phase of vascular disease and related to traditional atherosclerosis risk factors. Brachial artery diameter changes in response to hyperemia have been proposed recently as a noninvasive tool to assess endothelial function. To evaluate the reproducibility of brachial artery diameter measurements using ultrasound, we studied 12 healthy subjects (eight men and four women, mean age 37 +/- 9 years). An ATL HDI 3000 machine with a 5- to 10-MHz broadband transducer was used to image the right brachial artery at rest, approximately 4 cm above the elbow. Gray scale ultrasound and color Doppler long-axis images were recorded. Brachial arterial outer diameter (i.e., from anterior adventitia to posterior adventitia) and inner diameter (i.e., from anterior lumen-intima interface to posterior lumen-intima interface) were measured in each subject by two observers. An offline analysis system was used to make measurements at end-diastole from four cardiac cycles. Interobserver and intraobserver measurement variabilities (technical error rates) for brachial artery inner diameter were excellent, ranging from 2.5% to 3.8%. However, interobserver technical error rates for outer diameter measurements were significantly greater than those for inner diameter measurements, ranging from 16.3% to 22.1% (P < 0.001), presumably related to the difficulty in accurately defining the adventitial lines. There were no significant differences in interobserver and intraobserver variability for measurements made using gray scale and color Doppler-aided techniques. We conclude that interobserver and intraobserver reproducibility for brachial artery inner diameter measurements made from ultrasound images is excellent.
The effect of ethanol and carbon tetrachloride administration on hepatic lipid-soluble antioxidant activity

Abstract The influence of ethanol or carbon tetrachloride administration on lipid soluble antioxidant activity of liver as well as mitochondria and microsomes was studied in a further evaluation of the hypothesis of the lipid peroxidation concept of ethanol-induced hepatic cell injury. While total liver lipid soluble antioxidant activity was not significantly modified in either ethanol or carbon tetrachloride-treated groups, the mitochondrial, but not microsomal, antioxidant concentration was significantly reduced 2 hours after the administration of ethanol. In contrast, microsomal lipid soluble antioxidant activity was significantly decreased in carbon tetrachloride-treated rats, while mitochondrial antioxidant activity remained unaltered. The selective changes in lipid soluble antioxidant activity correlate well with the subcellular sites of ethanol- and carbon tetrachloride-induced lesions and with previous demonstrations of lipoperoxidation. The intraperitoneal administration of the lipid soluble antioxidant DPPD, produced a three- to four-fold increase in total liver lipid antioxidant levels, as well as a comparable increase in brain tissue. The mitochondrial antioxidant levels were slightly increased while a profound enhancement occurred in the microsomal fraction in the DPPD-treated groups. The elevated mitochondrial and microsomal antioxidant levels in the DPPD-treated group were not significantly altered by ethanol or carbon tetrachloride administration. In an effort to establish the usefulness of antioxidant loss as an index of the peroxidation process, a comparative study was made employing the thiobarbituric acid procedure, i.e., malonaldehyde formation, conjugated diene analysis, and lipid soluble antioxidant activity determinations. The model was normal rat liver homogenates incubated either in the presence of air, nitrogen, oxygen, or in the presence of lipoxidase. Measurements were made at 0, 30, 60, 120 minutes of incubation. Malonaldehyde formation occurred in the following order, nitrogen The present study further contributes to the concept that lipid antioxidants, such as DPPD exert their protective effect by their antioxidant activity exerted against an induced free radical attack at specific subcellular sites. While it remains to be established that the observed decline in antioxidant concentrations is sufficient to induce the mitochondrial or microsomal functional and ultrastructural aberrations which characterize acute ethanol or carbon tetrachloride administration, the present studies do extend the concept of lipid peroxidation in the pathogenesis of certain types of chemical induced hepatic injury and the possible role of antioxidants in the inhibition of injury.
Optimum inspection and maintenance policies for corroded structures using partially observable Markov decision processes and stochastic, physically based models

Abstract Stochastic control methods have a history of implementation in risk management and life-cycle cost procedures for civil engineering structures. The synergy of stochastic control methods and Bayesian principles can result in Partially Observable Markov Decision Processes (POMDPs) that allow consideration of uncertainty within the entire domain of the model and expand available policy options compared to other state-of-the art methods. The superior attributes of POMDPs enable optimum decisions which are based on the belief space or otherwise only on the best knowledge that a decision-maker can have at each time. In this work the effort is mostly based in modeling and solving the problem of finding optimal policies for the maintenance and management of aging structures through a POMDP framework with large state spaces that can adequately and sufficiently describe real-life problems. In order to form the POMDP framework, stochastic, physically based models can be used and their connection to the control process is explained in detail. Specific examples of a corroded existing structure are presented, based on non-stationary POMDPs, for both infinite and finite horizon cases with 332 and 14,009 states respectively. Results from both cases are compared and discussed and the capabilities of the method become apparent.
Narratives, facts, and events in the foundations of information science

This session explores three basic notions: events, facts, and narratives. Events play a large role in our lives. Our sense of identity is largely shaped by events we have experienced. Our understanding of history is a narrative of events in the past. The humanities and social sciences are concerned with the human experience, with actions and interactions. The sciences also deal with events: changes, processes, and experiments. Events may be described factually and themselves be regarded as facts. Facts, in turn, assume their full meaning only in relation to narratives, which provide the contextual frameworks for understanding them. In our daily lives we have little difficulty thinking and talking about events, facts, and narratives. However, information systems operate on objects (bits, data, documents). Events, facts, and narratives are not objects and difficulties arise when we try to analyze formally what they are. Three related papers address these issues. First, a direct examination of the nature of events; second, an account of two contrasting ways of contextualizing facts; and, third., an attempt to encode events in biographical narratives.
Exploring structures in protein folding funnels with free energy functionals: the denatured ensemble.

We discuss the formulation of free energy functionals that describe the formation of structure in partially folded proteins. These free energy functionals take into account the inhomogeneous nature of contact energies, chain entropy and cooperative contributions reflecting the many body character of some folding forces like hydrophobicity, but do not directly account for non-native contacts because they assume the validity of the minimal frustration principle. We show how the free energy functionals can be used to interpret experiments on partially folded proteins that probe the fractional occupancy of specific local structures. In particular, we study the hydrogen protection factors in lysozyme studied in transient experiments by Gladwin and Evans and by Nash and Jonas using equilibrium pressure denaturation and the NMR order parameters measured by Dobson and Kim for the homologous protein alpha-lactalbumin.
Contemporary Alternatives to Plant Estrogens for Menopause

Objectives Every year, millions of women begin the peri-menopause and may experience a number of symptoms related to this transition. Many women are reluctant to use exogenous hormone therapy for treatment of menopausal symptoms and are turning to botanical and dietary supplements (BDS) for relief. This paper reviews the literature on alternatives to plant estrogens for relief of menopausal symptoms.
Unilateral involvement of kidneys in mice infected with Candida albicans.

Mice injected with 103 cells of a virulent isolate of Candida albicans via the lateral tail vein developed frequent unilateral abnormalities of the right but not the left kidneys. Initially the number of colony forming units in the right and left kidneys were similar but number of colonies became consistently higher in the right kidneys as the infection progressed. The frequency of unilateral involvement decreased when the inoculum size was increased to 5×103 cells. These observations indicate that when growth of C. albicans in vivo is monitored over a period of time starting with a low inoculum, it is critical to be consistent in culturing kidneys from the same side.
Trace identities for solutions of the wave equation with initial data supported in a ball

Suppose u is the solution of the initial value problem u tt - Δ x u = 0, (x,t) ∈ R n × [0,∞) u(x, t=0) = f(x), u τ (x, t=0) = g(x), x ∈ R n Suppose n ≥ 1 is odd, f and g are supported in a ball B with boundary S, and one of f or g is zero. We derive identities relating the norm of f or g to the norm of the trace of u on S x [0,∞). These identities are derived using integral geometric and multiplier methods.
Structural similarities among cuprate superconductors

Abstract A general description is given of vacancy patterns in five compounds that contain unique oxygen vacancy patterns: LaSrCuGaO5, LaSrCuAlO5, YBa2Cu3O7, LnSr2Cu2Ga07, and Ba2La2Cu2Sn2O11. The structural similarity among the compounds is stressed by the presentation and examination of AO3−x slices. The influence of the cations on the manner in which successive AO3−x layers are stacked is discussed.
Down regulation of β-receptors by bupropion and its major metabolite in mouse brain

Abstract Mice were treated with bupropion Compound II (major metabolite of bupropion) or desmethylimpramine (DMI) twice a day intraperitoneally for either 1 or 3 weeks. The binding of dihydroalprenolol and spiroperidol in the frontal cortex and limbic forebrain areas were analyzed. There was a significant reduction in β-receptors in the frontal cortex induced by DMI at both times examined. Bupropion showed a significant reduction of β-receptor in the frontal cortex by 3 weeks. Though propiophenone did not have any significant effect on β-receptors in the frontal cortex, it down-regulated β-receptors in the limbic forebrain area significantly by 1 and 3 weeks. There was no significant effect of buropion or propiophenone on the binding of spiroperidol either in the cortex (S2 receptor) or in the limbic forebrain (dopaminergic). These results show that bupropion may exert part of its clinical effect through its metabolite propiophenone.
Dimethyl Fumarate, an Immune Modulator and Inducer of the Antioxidant Response, Suppresses HIV Replication and Macrophage-Mediated Neurotoxicity: A Novel Candidate for HIV Neuroprotection

Despite antiretroviral therapy (ART), HIV infection promotes cognitive dysfunction and neurodegeneration through persistent inflammation and neurotoxin release from infected and/or activated macrophages/microglia. Furthermore, inflammation and immune activation within both the CNS and periphery correlate with disease progression and morbidity in ART-treated individuals. Accordingly, drugs targeting these pathological processes in the CNS and systemic compartments are needed for effective, adjunctive therapy. Using our in vitro model of HIV-mediated neurotoxicity, in which HIV-infected monocyte-derived macrophages release excitatory neurotoxins, we show that HIV infection dysregulates the macrophage antioxidant response and reduces levels of heme oxygenase-1 (HO-1). Furthermore, restoration of HO-1 expression in HIV-infected monocyte-derived macrophages reduces neurotoxin release without altering HIV replication. Given these novel observations, we have identified dimethyl fumarate (DMF), used to treat psoriasis and showing promising results in clinical trials for multiple sclerosis, as a potential neuroprotectant and HIV disease-modifying agent. DMF, an immune modulator and inducer of the antioxidant response, suppresses HIV replication and neurotoxin release. Two distinct mechanisms are proposed: inhibition of NF-κB nuclear translocation and signaling, which could contribute to the suppression of HIV replication, and induction of HO-1, which is associated with decreased neurotoxin release. Finally, we found that DMF attenuates CCL2-induced monocyte chemotaxis, suggesting that DMF could decrease recruitment of activated monocytes to the CNS in response to inflammatory mediators. We propose that dysregulation of the antioxidant response during HIV infection drives macrophage-mediated neurotoxicity and that DMF could serve as an adjunctive neuroprotectant and HIV disease modifier in ART-treated individuals.
Nutritional Status and Cardiac Mass and Function in Children Infected with the Human Immunodeficiency Virus. ♦ 498

Nutritional Status and Cardiac Mass and Function in Children Infected with the Human Immunodeficiency Virus. ♦ 498
Forming agents for business process orchestration

Distributed component-based services and semantic Web services are promising technologies for next generation inter-enterprise integration. The dynamic nature of this domain presents a complex problem for potential software agent-based approaches that support this cross-organizational integration. Currently, there are few studies that measure the impact of the dynamic environmental effects on service composition. On an on-going basis, composite services or workflow processes of Web services may be constantly changing in terms of responsiveness of services, accessibility of services and their meta-information, business process schema changes, etc. This paper describes an approach, model, and supporting software toward the efficient formation of agent teams and interaction protocols for business process orchestration in response to certain environmental conditions.
Development and validation of an instrument to measure student knowledge gains for chemical and physical change for grades 6–8

Teachers tend to instruct topically, which requires the student to use multiple and interconnected concepts to succeed in each instructional unit. Therefore, it is beneficial to combine research on related concepts to form topic driven instruments to better assist teachers in assessing and instructing students. Chemical and physical change as a topic is often students' first introduction to chemical reactions; however, understanding the distinction is contingent upon a host of advanced ideas. As such, chemical and physical change is best evaluated with a strong emphasis on particle properties and behavior. To date, there was no instrument specifically designed for grades 6–8 (ages 11–14) that focused on the topic of chemical and physical change including its underlying conceptions such as the particulate nature of matter. By making use of well-designed and tested items from previously published research and item repositories, the chemical and physical change assessment (CPCA) was designed to translate findings from research to a practical and classroom-ready assessment. The CPCA went through two versions to result in a 19-item assessment that has generated valid and reliable data to date. Revisions to the assessment were driven by psychometric properties of the items as well as student validation interviews.
Harmony: an execution model and runtime for heterogeneous many core systems

The emergence of heterogeneous many core architectures presents a unique opportunity for delivering order of magnitude performance increases to high performance applications by matching certain classes of algorithms to specifically tailored architectures. Their ubiquitous adoption, however, has been limited by a lack of programming models and management frameworks designed to reduce the high degree of complexity of software development intrinsic to heterogeneous architectures. This paper proposes Harmony, a runtime supported programming and execution model that provides: (1) semantics for simplifying parallelism management, (2) dynamic scheduling of compute intensive kernels to heterogeneous processor resources, and (3) online monitoring driven performance optimization for heterogeneous many core systems. We are particulably concerned with simplifying development and ensuring binary portability and scalability across system configurations and sizes. Initial results from ongoing development demonstrate the binary compatibility with variable number of cores, as well as dynamic adaptation of schedules to data sets. We present preliminary results of key features for some benchmark applications.
Hierarchical test generation: Taking boundary scan to the next level

Development of the original IEEE 1149.1 boundary-scan standard in 1990 was motivated primarily by concerns about the complexity of testing increasingly dense printed-circuit board assemblies in manufacturing. As a result, most test generation efforts have been targeted at unit test, which is most applicable to testing MCMs and boards. As boundary-scan technology has matured, there is a new focus on extending the technique to testing all levels of an assembly's hierarchy, at all phases in its life cycle.
Genomic dark matter

Motivation: Genome resequencing and short read mapping are two of the primary tools of genomics and are used for many important applications. The current state-of-the-art in mapping uses the quality values and mapping quality scores to evaluate the reliability of the mapping. These attributes, however, are assigned to individual reads and do not directly measure the problematic repeats across the genome. Here, we present the Genome Mappability Score (GMS) as a novel measure of the complexity of resequencing a genome. The GMS is a weighted probability that any read could be unambiguously mapped to a given position and thus measures the overall composition of the genome itself. Results: We have developed the Genome Mappability Analyzer to compute the GMS of every position in a genome. It leverages the parallelism of cloud computing to analyze large genomes, and enabled us to identify the 5–14% of the human, mouse, fly and yeast genomes that are difficult to analyze with short reads. We examined the accuracy of the widely used BWA/SAMtools polymorphism discovery pipeline in the context of the GMS, and found discovery errors are dominated by false negatives, especially in regions with poor GMS. These errors are fundamental to the mapping process and cannot be overcome by increasing coverage. As such, the GMS should be considered in every resequencing project to pinpoint the ‘dark matter’ of the genome, including of known clinically relevant variations in these regions. Availability: The source code and profiles of several model organisms are available at http://gma-bio.sourceforge.net Contact: hlee@cshl.edu Supplementary Information: Supplementary data are available at Bioinformatics online.
Myths in anesthesiology.

The article by Soppitt et al. in this issue concludes that “many anesthesiologists use a single dose of propofol in expectation of an antiemetic effect, even though scientific evidence supporting this is lacking”. Specifically, this article sets forth that 84% of all surveyed participants use propofol for its antiemetic effect, with 63% using that drug in procedures lasting more than one hour. Curiously enough, this is despite results of recent scientific studies that have conclusively shown that the plasma level of propofol after one hour’s duration is well below any effective concentration. In other words, it appears that a majority of anesthesiologists are using the drug for an ineffectual purpose. Assuming that randomly questioned anesthesiologists are a representative sample of the anesthesia community, a majority of anesthesiologists have incorporated a false belief into their daily routine. False beliefs or myths of any type are rarely written down; rather, they are passed down through generations, leading one to ask: How do these myths or false beliefs develop among anesthesiologists? Despite existing standards in monitoring, pharmacology, and better understanding of physiology, much of the practice of anesthesiology still remains largely a clinical art, with further advancement dependent on quality of research and education. Research—animal or human—is stimulated mostly by the intellectual curiosity of individuals who desire to verify or refute clinical experience. Research is conducted at research institutions, medical schools, and independent industrial research departments, and the outcome is integrated into lectures at residency programs, presentations at scientific conferences, publication in medical journals, audiovisual material, reinforced in part by representatives of industries manufacturing either drugs or equipment. How significant is the contribution of each of these vehicles in disseminating the scientific based evidence or creating myths? Lectures in anesthesiology residency programs include results of scientific studies; however, even in the academic environment, daily activities are not always based on scientific methods. Primarily because institutional biases and attending anesthesiologists’ personal experiences affect daily practice, residents are not always taught material that has supporting evidence. Such false or unsupported beliefs are then reinforced by repetition, until they become habit and convenience. Eventually graduate residents carry them to their respective practices. Pharmaceutical companies affect daily practice of all physicians, not only anesthesiologists. Interaction between physicians and pharmaceutical companies starts as early as medical school and continues well into practice. Numerous studies have been conducted, and articles published about the results of that interaction show that the relationship between practitioners and companies has an impact on the rapid introduction of new drugs and their prioritization. Although none of the studies referred to in a recent review article, have shown
Mode use in deaf children: the effects of communication method and communication competence

This study examined the differential mode usage (speech, vocalize, gesture and sign) of profoundly deaf preschoolers and their hearing mothers as a function of their level of communicative competence (high vs. low) and method of communication (simultaneous vs. oral). Language and mode use of twenty-eight hearing mother/deaf child dyads (equally divided into oral and simultaneous dyads) were recorded during free play. Findings indicated significant mode use differences as a result of both method of communication and level of competence within each method. Bimodal or simultaneous use of modes was related to both higher communicative competence in both oral and simultaneous children and specific pragmatic types of communication. Findings are discussed in relation to both theoretical and applied issues in understanding early childhood deafness.
Control of nonholonomic systems with dynamically decoupled actuators

A compensator is derived for a class of nonholonomic systems incorporating both dynamically coupled and uncoupled actuators. The compensator affords exponential convergence to smooth trajectories in a reduced state space. >
Cigarette smoking and rheumatoid arthritis severity

OBJECTIVES—Cigarette smoking may influence rheumatoid arthritis (RA) disease incidence and may have direct biological effects on the lungs and systemically. This study sought to determine if cigarette smoking is associated with RA disease severity. METHODS—Clinical evaluations of patients seen in the University of Iowa rheumatology and orthopaedic ambulatory clinics were conducted. A letter of interest was mailed to 1701 patients who were first assigned an ICD-9-CM diagnostic code for RA in one of these clinics. A total of 857 patients expressed interest and were offered a clinical examination and 395 were evaluated over an 18 month period. Of these, 336 satisfied examiner criteria for prevalent RA and were included in the analysis. The disease characteristics and arthritis care utilisation of these patients seemed representative of prevalent cases in the general community. RA disease severity was assessed by radiographic bone erosions (graded as either present/absent and using the Larsen system), rheumatoid factor seropositivity, and presence of subcutaneous rheumatoid nodules. RESULTS—Pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity (p = 0.0001), radiographic erosions (p = 0.024), and nodules (p = 0.051). After adjustment for potential confounders, smokers with ≥25 pack years were 3.1 times more likely to be rheumatoid factor positive (95% CI 1.7, 5.6) and 2.4 times more likely to show radiographic erosions (95% CI 1.2, 4.5) than never smokers. Less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease. CONCLUSION—Cigarette smoking may adversely influence the severity of RA in a potentially dose dependent fashion.
Cross-protection elicited in channel catfish (Ictalurus punctatus Rafinesque) immunized with a low dose of virulent Edwardsiella ictaluri strains

Cross-protection of channel cat¢sh (Ictalurus punctatus Ra¢nesque) immunized with a low dose of virulent Edwardsiella ictaluri and challenged with six E. ictaluri strains was examined in four trials. The relative per cent survival among low-dose immunized and then challenged ¢sh ranged from 27.7% to 100%. Signi¢cant protection (Po0.05), with the exception of strain ATCC-33202, was conferred by immunization with a given E. ictaluri strain challenged either with a homologous or a heterologous strain. Antibody titres of pooled serum collected on day 22 from surviving ¢sh examined by enzyme-linked immunosorbent assay (ELISA) ranged from 1:40 to 1:320, but no diierences were apparent among diierent vaccinated groups. The protein pro¢les of six E. ictaluri strains examined by Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDSPAGE) showed a relatively homogeneous pattern. Immuno-blots probed with pooled serum from immunized and challenged ¢sh showed a pattern similar to LPS-reaction patterns observed with E. ictaluri in other studies. Since the present studies further corroborate that E. ictaluri is a clonal bacterial species with no apparent antigenic diierences, it is possible that immunization with a single E. ictaluri ¢eld strain should confer protection against any other strain.
BRAIN PARENCHYMAL AND MICROVASCULAR AMYLOID IN ALZHEIMER'S DISEASE

Brains of patients with Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily in the form of characteristic parenchymal 'plaques' (senile or neuritic plaques/SP's) and as mural deposits in the walls of capillaries and arterioles (cerebral amyloid angiopathy /CAA). A major component of this amyloid is a small and unique peptide composed of 39-43 amino acids, beta/A4, which is cleaved from a much larger precursor protein (APP) that has several isoforms. Brain amyloid can be detected in autopsy or biopsy brain tissue by classical, immunohistochemical and ultrastructural (including immuno-electron microscopic) methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is remarkably variable (e.g. predominantly parenchymal or vascular, or a mixture of parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis of the neurological deficit, neocortical atrophy and progressive synapse loss associated with AD/SDAT has yet to be determined. However, mutations in the gene that encodes APP are clearly associated with familial AD syndromes in which there is significant brain amyloid deposition. CAA, in addition to its association with AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work with recently developed transgenic mice which express large amounts of beta/A4 in the central nervous system is likely to elucidate mechanisms by which the protein is selectively or deposited in the brain in a parenchymal or microvascular form, and how it contributes to the pathogenesis of neurodegeneration.
Definition and application of approximate necessary assignments

A necessary assignment for a fault f is a line value that must be assigned by a test vector that detects f. A higher number of necessary assignments translates into a lower test generation effort since the test generation process has a larger number of values that it must assign, and therefore, fewer options that it can explore. To increase the number of available necessary assignments, we define approximate necessary assignments as line values that are assigned by most of the test vectors for a fault. We describe a heuristic procedure for computing approximate necessary assignments for inputs and demonstrate their effectiveness in reducing the test generation effort of a random test generation process.