cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinical consequences of analytical variance and calculation strategy in oral busulfan pharmacokinetics

Abstract Background Busulfan pharmacokinetic (PK) monitoring of the area under the concentration–time curve (AUC) is necessary to minimize adverse events associated with both under- and over-dosing of busulfan during hematopoietic stem cell transplantation (HSCT). Three strategies are frequently used to calculate the AUC including in-house polynomial methods, the trapezoidal method (also called noncompartmental analysis), and the single compartment model with first-order elimination method. We compared these 3 methods, their clinical performance, and the relationship of AUC variance to analytical variance when each of these methods is used. Methods Clinical busulfan PK data was reviewed from 159 patients receiving the first dose of oral busulfan while undergoing HSCT. These data were used as templates to simulate AUC results and actions with varying amounts of analytical precision. Results Based on a predefined goal therapeutic target, the method for calculating AUC significantly changed the number of recommended busulfan dose adjustments (p Conclusion Analytical variance and the AUC calculation method play a considerable role in the clinical management of busulfan dosing during HSCT. With better understanding and optimization of the analytical method, the reliability of clinically actionable information from busulfan PK can increase.
Extensive electron-nuclear angular momentum exchange in vibrational autoionization of np and nf Rydberg states of NO.

Vibrational autoionization of individual rotational levels of {ital np} ({nu}=1) and {ital nf} ({nu}=1) Rydberg states of nitric oxide (NO) with 11{le}{ital n}{le}15 have been studied employing two-color double-resonance excitation via the NO {ital A}{sup 2}{Sigma}{sup +} ({nu}{sub {ital i}}=1) state. The rotational state distributions of the resulting NO{sup +} {ital X}{sup 1}{Sigma}{sup +} ({nu}{sup +}=0) ion have been determined by time-of-flight photoelectron spectroscopy. These measurements show the occurrence of angular momentum exchange between the outgoing electron and the molecular-ion core, a process that has been commonly neglected in theoretical treatments of vibrational autoionization. {copyright} {ital 1996 The American Physical Society.}
Toward a preliminary macro theory of drug addiction

Currently, the drug addiction literature is replete with micro‐level theories of addiction that offer important insights into individual and small‐group processes leading to addiction. However, few offer much consideration of macro‐level matters (e.g., social structural and cultural). Macro theories of addiction are even more scarce. This inattention to macro‐level factors may ultimately impede the ability to reduce addiction and related social problems. The purpose of this article is to offer preliminary formulations for a macro theory of drug addiction. A critique of leading micro‐oriented theories, coupled with Hall and Jefferson's (1976) Cultural Studies school, helps facilitate this effort. The discussion centers on drug subcultures instead of individual addicts and brings macro‐level matters (e.g., economic and social inequality and cultural norms and values) to the center of the debate. Furthermore, the new theoretical formulations offer important insights into rates of addiction among population s...
Complications of the Percutaneous Kidney Biopsy

Percutaneous kidney biopsy is an integral part of a nephrologist's practice. It has helped to define nephrology as a subspecialty. When indicated, it is a necessary procedure to help patients, as it allows for diagnostic, prognostic, and therapeutic information. Although very safe, this procedure can give rise to complications, mainly related to bleeding. Since its development in the 1950s, modifications have been made to the approach and the technique, which have improved the diagnostic yield while keeping it a safe procedure. Alterations to the standard approach may be necessary if risk factors for bleeding are present. In addition, obesity, pregnancy, and solitary kidney biopsy are all special circumstances that change the procedure itself or the risk of the procedure. Today, kidney biopsy is a vital procedure for the nephrologist: clinically relevant, safe, and effective.
Comments on: Intensity modulated radiation therapy treatment plan optimization

Cancer is the second leading cause of death and it is blamed for 25% of deaths in the U.S. (American Cancer Society 2008). As mentioned by the authors, approximately 1.4 million people in the U.S. will be newly diagnosed with cancer this year. This year alone, about 565,650 Americans are expected to die of cancer, which is about 1,550 people a day.
Wavelength generalization and discrimination in the pigeon

This three-part study describes wavelength generalization gradients around a series of training wavelengths ranging from 480 to 645 om. Luminance was controlled for the pigeon's spectral sensitivity. The response measure was probability of keypecking during a 2-sec stimulus presentation. Both an extinction procedure, where stimulus wavelengths occurred in 15-nm steps, and a maintained discrimination procedure, where step size was 2 to 4 om, were used to obtain gradients. During a portion of the maintained discrimination procedure, new luminances were introduced, so that the effect of luminance level on gradient slope could be examined. Comparison of the resulting functions across training wavelengths revealed: (1) consistent differences in gradient slope in different spectral regions and (2) an increase in slope with luminance increase. The findings are related to recent electroretinographic wavelength contrast data and to psychophysical measures of wavelength discriminability. The way in which discriminability relates to stimulus generalization, although much discussed in the past, has remained unclear. Some principal experiments in this field have dealt with the wavelength dimension in pigeons (Guttman & Kalish, 1956) and in humans (Kalish, 1958). These studies examined generalization gradients in various areas of the spectrum and compared the findings with appropriate wavelength
Synchroneity of tropical and high-latitude Atlantic temperatures over the last glacial termination.

A high-resolution western tropical Atlantic sea surface temperature (SST) record from the Cariaco Basin on the northern Venezuelan shelf, based on Mg/Ca values in surface-dwelling planktonic foraminifera, reveals that changes in SST over the last glacial termination are synchronous, within ±30 to ±90 years, with the Greenland Ice Sheet Project 2 air temperature proxy record and atmospheric methane record. The most prominent deglacial event in the Cariaco record occurred during the Younger Dryas time interval, when SSTs dropped by 3° to 4°C. A rapid southward shift in the atmospheric intertropical convergence zone could account for the synchroneity of tropical temperature, atmospheric methane, and high-latitude changes during the Younger Dryas.
Mixture model framework facilitates understanding of zero-inflated and hurdle models for count data.

In this note, we comment on the zero-inflated and hurdle models for count data presented by Rose et al., 2006, J. Biopharma. Stat. 16:463–481. By viewing these models as finite mixture models, one gains a better understanding of the components of the models, including assumptions about the latent variable(s) in the finite mixture models. Deciding whether a zero-inflated or hurdle model is appropriate for a given data set requires close collaboration with subject matter experts. For instance, in modeling vaccine adverse event count data, the pharmacokinetic rationale for the occurrence of an adverse event and the likelihood of detecting or reporting the adverse event are important considerations for mixture model development.
Inhibition of the proteolytic contaminant in commercial xanthine oxidase preparations by serum protein fractions

Abstract Commercial xanthine oxidase, widely used for generation of oxygen radicals in vitro, is usually contaminated by proteolytic activity, which limits its utility in studies of oxygen radical damage to protease sensitive substrates. An easily prepared fraction of fetal calf serum was found to inhibit virtually all of the proteolytic contaminant without affecting superoxide generation. The effects attainable with the “purified” enzyme were demonstrated with two protease sensitive targets: proteoglycan subunit from cartilage and fibronectin from human plasma.
Laser plasma sources for soft x-ray projection lithography

Compact laser plasma soft x-ray sources are under serious consideration for projection lithography. Current baseline designs for soft x-ray projection lithography systems place stringent performance and cost requirements on a laser plasma soft x-ray source. The x-ray source must meet specific criteria relating to x-ray fluence in the 13 nm region, the wavelength of preference for projection lithography, to output stability at high (kHz) repetition-rates, to continuous long term operation and to operating costs. Moreover the source must operate in a vacuum enclosure in close proximity to costly x-ray and optical elements which must remain in pristine condition, free from degradation by particulate and plasma emission emanating from the source. We discuss these requirements, and review experiments leading to the optimal design of a laser plasma soft x-ray source.
100 curricula in electrical engineering

During the past decade a great many changes have taken place in the engineering schools and still other changes are in progress today. The results of an analysis of the curricula of more than 100 colleges offering courses in electrical engineering are presented.
Architecture initiatives: component-based simulation modeling

This paper presents a component-based framework for designing simulation models and discusses its implementation in a package called Simkit. In this framework, Components are defined to be monolith software entities that interact with other components in one of only three ways. Although seemingly restrictive, this approach supports more extensibility and customization of simulation models than conventional Object-Oriented design.
Intake of fatty acids and antioxidants and pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area

There are no well-established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p(trend) or=0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25-0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51-0.94); p(trend) = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49-0.92); p(trend) = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p(trend) < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega-3 fatty acids, vitamins C and E may reduce the risk.
Occupational, Industrial and Environmental Toxicology

edited by Michael I. Greenberg, Richard J. Hamilton, and Scott D. Phillips, 1997, Mosby, St. Louis, MO, 620 pages; $89.95.edited by Michael I. Greenberg, Richard J. Hamilton, and Scott D. Phillips, 1997, Mosby, St. Louis, MO, 620 pages; $89.95.
Education for Citizenship in Romania and the UK: A Comparison

The article compares the development of Citizenship Education in the United Kingdom and Romania since 1989, the year when Communism was overthrown in several Eastern European countries including Romania (and when, coincidentally, Citizenship made its first formal appearance in the English National Curriculum as a cross-curricular theme). Findings are presented from two case study high schools, one in the UK and one in Romania. Staff and students offer views on the nature of citizenship, on how Citizenship Education might be taught in school and on issues influencing the development of a programme to help students become effective individuals with a commitment to community participation in its broadest sense. The analysis develops the view that, if Citizenship Education is to make a genuine contribution to the creation of a vibrant, participatory democracy in which young people are fully involved, the structures and processes via which Citizenship Education is devised and delivered should themselves reflect the principles of democratic participation.
Value of proctoscopy in the diagnosis of amebiasis

A study of 115 consecutive patients who had amebic dysentery was carried out for the purpose of determining how much value proctoscopy has in the diagnosis of the condition.
The “reputation” of neoliberalism

“Flexibility” has been described as the cornerstone of the current neoliberal agenda—embodied in mandates for the fluid movements and restructuring of labor, capital, and information and, at the individual level, in a supple capacity for creative self-invention and self-mastery. Flexibility is also a central quality revered within a realm of oppositional cultural practice known in the analytical paradigm of Caribbean anthropology as “reputation.” What is striking about these different logics of flexibility is that one (reputational flexibility) is grounded in a set of cultural values of the Caribbean subaltern in opposition to bureaucratic hierarchy and (neo)colonial domination, and the other (neoliberal flexibility) sits firmly in the center of contemporary global capitalist orthodoxy. On the basis of fieldwork I conducted between 2001 and 2006, I argue that the quest for flexibility among emergent middle-class entrepreneurs in Barbados represents a new path of opportunity and upward mobility as well as a gendered tightrope of respectability. In this quest, I argue, these entrepreneurs are redefining the dialectics of reputation–respectability and class in Barbados and the cultural meanings of neoliberalism itself.
Specificity of inhibition of ras-p21 signal transduction by peptides from GTPase activating protein (GAP) and the son-of sevenless (SOS) ras-specific guanine nucleotide exchange protein.

In previous studies, involving molecular modeling of wild-type and oncogenic forms of the ras-p21 protein bound to GTPase activating protein GAP and the ras-specific guanine nucleotide exchange-promoting protein, SOS, we identified specific domains of GAP and SOS proteins that differ in conformation when the computed average structures of the corresponding wild-type and oncogenic complexes are superimposed. Additionally, in these previous studies, we have synthesized peptides corresponding to these domains and found that all of them inhibit either or both oncogenic (Val 12-containing) p21- and insulin-activated wild-type p21-induced oocyte maturation. To document further the specificity of the inhibition of these peptides for the ras signal transduction pathway, we have now tested their effects on progesterone-induced maturation that occurs by a ras-independent pathway. None of these peptides, including a peptide corresponding to residues 980–989 of SOS that completely blocks oncogenic p21-induced maturation and also causes extensive inhibition of insulin-induced maturation, affects progesterone-induced maturation, suggesting that all of these peptides are specific for the ras pathway. Since our approach to the design of peptides that can inhibit oncogenic ras-p21 selectively is based on identifying domains that differ in conformation between oncogenic and wild-type complexes, we have now further synthesized peptides that correspond to domains of GAP (residues 903–910) and SOS (residues 792–804) that do not differ in conformation when the average structures are superimposed. These peptides do not inhibit either oncogenic p21- or insulin-induced oocyte maturation, supporting the overall strategy of using peptides from domains that change conformation as the ones most likely to inhibit oncogenic and/or wild-type ras-p21. These results further support the specificity of inhibition of the GAP and SOS peptides from the conformationally distinct domains of both proteins.
Response thresholds to sucrose predict foraging division of labor in honeybees

Division of labor, where thousands of individuals perform specific behavioral acts repeatedly and non-randomly, is the hallmark of insect societies. Virtually nothing is known about the underlying neurophysiological processes that direct individuals into specific behavioral roles. We demonstrate that sensory-physiological variation in the perception of sucrose in honeybees measured when they are 1 week old correlates with their foraging behavior 2–3 weeks later. Workers with the lowest response thresholds became water foragers, followed with increasing response thresholds by pollen foragers, nectar foragers, bees collecting both pollen and nectar, and finally those returning to the colony empty (water<pollen<nectar<both<empty). Sucrose concentrations of nectar loads were positively correlated with response thresholds measured on 1-week-old bees. These results demonstrated how the variable response thresholds of a sensory-physiological process, the perception of sucrose, is causally linked to the division of labor of foraging.
STUDIES IN ACROMEGALY II. HISTORICAL NOTE

Owing to the protean nature of the disease acromegaly, the literature concerning it has grown extremely voluminous. Each one who had an opportunity to investigate the clinical picture or post-mortem findings in a personally observed case was apt to stress the outstanding features presented by his particular patient, with a resulting confusion of opinions regarding the nature and origin of this strange malady. There have thus grown up “schools” of opinion, each championed by some outstanding contributor whose numerous followers have all inserted their personal modifications to the original hypotheses. It is not the aim of this present note to review the entire literature on the subject of acromegaly, but merely to touch upon those points which appear to be essential to our present conception of the disease. The paper therefore will serve merely as an introduction to certain studies concerning diabetes, metabolism, the rOle of other endocrine organs than the hypophysis, etc., which are to follow.
Single-Frame Chemical Imaging: Dimension Reduction Fiber-Optic Array Improvements and Application to Laser-Induced Breakdown Spectroscopy:

A single-frame approach to chemical imaging with high spectroscopic resolution is described that makes use of a second-generation dimension-reduction fiber-optic array. Laser-induced plume images are focused onto a 17 X 32 rectangular array of square close-packed 25 mu m cross-sectional f/2 optical fibers that are drawn into a 544 X 1 distal array with serpentine ordering. The 544 X 1 side of the array is imaged with an f/2 spectrograph equipped with a holographic grating and a gated intensified charge-coupled device (ICCD) camera for spectral analysis. Software is used to extract the spatial/spectral information contained in the ICCD images and deconvolute them into wavelength-specific univariate reconstructed images or position-specific spectra that span an 86 nm wavelength space. Temporal resolution is provided by imaging sequential laser plumes with varying time delays after each laser pulse on the gated intensifier.
Evidence that pcpA encodes 2,6-dichlorohydroquinone dioxygenase, the ring cleavage enzyme required for pentachlorophenol degradation in Sphingomonas chlorophenolica strain ATCC 39723.

An enzyme that catalyzes an Fe2+-dependent reaction of 2,6-dichlorohydroquinone with O2 has been isolated from Sphingomonas chlorophenolica sp. strain ATCC 39723, a soil microorganism capable of complete mineralization of pentachlorophenol. The product of the reaction is too unstable to allow spectroscopic characterization, but is apparently negatively charged and retains the two chlorine atoms of the substrate. The enzyme was partially sequenced using electrospray LC−MS, and one peptide was used to search the NCBInr database. This peptide matched a part of PcpA, a protein of unknown function that is induced in S. chlorophenolica in response to pentachlorophenol. Several other peptides could also be mapped onto the sequence of PcpA, suggesting that the enzyme is encoded by pcpA. PcpA has low but significant sequence similarity to an unusual class of extradiol dioxygenases. On the basis of the sequence analysis, the Fe2+ and O2 dependence of the enzyme, and the characteristics of the product, the enzyme is...
Radiozinc studies in experimental wound healing.

Summary Studies of radiozinc retention in experimental wound healing have been carried out in rats with incised abdominal wounds and excised back wounds. A prefeential accumulation of radioctivity was demonstrated in the acute healing stage of incised wounds, coinciding with the development of vascularity and biochemical alterations. Measurements made on the scar connective tissue of the excised wounds after 100 days showed very low retention of radiozinc compared to the surrounding skin and hair.
Born-Type Rigid Motion in Relativity

Rigid motions of collections of particles as defined by Born, Herglotz, and Noether are studied in special and general relativity. An approximate method for solving the field equations of general relativity, the equations of motion of a perfect fluid undergoing a rigid motion, and the boundary condition $p=0$ is described and the first-order solution for the first two sets of equations is obtained. It is shown that in the classical limit the boundary conditions may be satisfied to this order.
Plant biology in the future

In the beginning of modern plant biology, plant biologists followed a simple model for their science. This model included important branches of plant biology known then. Of course, plants had to be identified and classified first. Thus, there was much work on taxonomy, genetics, and physiology. Ecology and evolution were approached implicitly, rather than explicitly, through paleobotany, taxonomy, morphology, and historical geography. However, the burgeoning explosion of knowledge and great advances in molecular biology, e.g., to the extent that genes for specific traits can be added (or deleted) at will, have created a revolution in the study of plants. Genomics in agriculture has made it possible to address many important issues in crop production by the identification and manipulation of genes in crop plants. The current model of plant study differs from the previous one in that it places greater emphasis on developmental controls and on evolution by differential fitness. In a rapidly changing environment, the current model also explicitly considers the phenotypic variation among individuals on which selection operates. These are calls for the unity of science. In fact, the proponents of "Complexity Theory" think there are common algorithms describing all levels of organization, from atoms all the way to the structure of the universe, and that when these are discovered, the issue of scaling will be greatly simplified! Plant biology must seriously contribute to, among other things, meeting the nutritional needs of the human population. This challenge constitutes a key part of the backdrop against which future evolution will occur. Genetic engineering technologies are and will continue to be an important component of agriculture; however, we must consider the evolutionary implications of these new technologies. Meeting these demands requires drastic changes in the undergraduate curriculum. Students of biology should be trained in molecular, cellular, organismal, and ecosystem biology, including all living organisms.
Dissociation dynamics in hyperthermal energy molecular ion/surface collisions

Abstract The processes of electron transfer and dissociative scattering are explored for collisions of state-selected hyperthermal energy (5–80 eV) NO+(X1Σ+, ν) on GaAs(110) and Ag(111). In conjunction with classical and quantum mechanical calculations, the experimental data reveal the sequence of neutralization, dissociation, and electron attachment steps responsible for the emergence of O−(2P) ions. This mechanism is compared to those which govern the formation of negative ion fragments in the scattering of state-selected OCS + (X 2 II 3 2 ) on Ag(111). In the scattering of OCS+, impulsive mechanical dissociation forms O−(2P) ions; dissociative neutralization leads to S−(2P); and atom elimination yields SO−(2II).
Peroxisome proliterators and cancer: mechanisms and implications

Abstract Plasticizers (e.g. di-(2-ethylhexyl)-pthalate (DEHP)) in common use in PVC plastics and hypolipidemic drugs (e.g. clofibrate) are two types of compound is to which we may be frequently exposed. Yet these are among a group of diverse compounds which cause hepatic peroxisome proliferation, a condition which can lead to hepatic cancer by non-mutagenic means. Janardan Reddy and Sambasiva Rao discuss the possible mechanisms of induction of peroxisome proliferator pleiotropic responses leading to the development of liver tumors, focusing in particular on the hypothesis that the mechanism involves a single biological receptor, or a set of receptors.
Association of star-shaped poly(D,L-lactide)s containing nucleobase multiple hydrogen bonding.

A new family of associating polymers based on four-arm, star-shaped poly(d,l-lactide) (PDLLA) containing peripheral complementary hydrogen-bonding sites is described. Hydroxy-terminated, four-arm, star-shaped PDLLAs of controlled molar mass were functionalized with complementary DNA base pairs, adenine (A) and thymine (T), to obtain PDLLA−A and PDLLA−T, respectively. 1H NMR spectroscopy confirmed quantitative functionalization and the subsequent formation of PDLLA−A and PDLLA−T hydrogen-bonded complexes. Job's analysis revealed a 1:1 optimal stoichiometry for the hydrogen-bonded complexes, and the association constant (Ka) that was determined using the 1H NMR-based Benesi−Hildebrand treatment was 84 M-1 for the low molar mass complementary polymers. Furthermore, the PDLLA-based hydrogen-bonded complexes exhibited higher solution viscosities compared to the corresponding non-hydrogen-bonded precursors, which further confirmed strong complementary multiple-hydrogen-bonding associations between the star-shap...
On symbolic manipulation and code generation of a hybrid three-dimensional solid element

A symbolic procedure is utilized to derive the analytical expressions of the component matrices resulting to the closed-form integration of a stiffness matrix of a hybrid finite element. In order to alleviate the expression growth problem, we employ special techniques, including the use of symmetry conditions, pattern search, and introduction of intermediate variables, so that the final form of the derived stiffness matrix is suitable for coding implementation. Application of the symbolic procedure is made on a hybrid three-dimensional 8-node solid element. The same procedure is equally applicable to other types of hybrid elements.
Forbidden coupling and inhibited decay: A study of disconnected quark diagrams

An attempt is made to correlate deviation from ideal-mixing mass formula, high-energy scattering behavior, and violation of the Okubo-Zweig-Iizuka rule. Pole or cut nature of the intermediary is discussed. Timelike and spacelike forbidden communications are compared. Off-shell effects are examined. Some problems for phenomenology are revealed.
Ecological genetics of Bromus tectorum. II. Intraspecific variation in phenotypic plasticity.

For Bromus tectorum, an alien annual grass now widespread in western North America, we assessed the sensitivity of the phenotypic expression of populational differences in phenology and demography to variation in plant density. Plants were grown in an unheated glasshouse from seeds collected from six habitat types located along a moisture-temperature gradient. Survival to flowering was high with a mean overall survival of 91%. Survival was highest among plants from the coolest, most mesic site. Time to first flowering decreased at the higher sowing density and was dependent on seed source. Plant dry weight and average seed production was lowest within high density plots; the magnitude of this reduction was significantly dependent on seed source. Individual seed weight was also dependent on the interaction of seed source and sowing density. Seed weight did not vary as much as seed number or plant weight in response to density. Differences among sources in hierarchies of plant size and seed production were detected at low sowing densities. The degree of inequality in the distributions of plant size and seed number increased at high density.
Dietary administration of 2(3)-t-butyl-4-hydroxyanisole elevates mouse liver microsome-mediated DNA binding and mutagenicity of aflatoxin B1.

Abstract Administration of the phenolic antioxidant 2(3)- t -butyl-4-hydroxyanisole (BHA) to mice resulted in a 2–3-fold increase in the liver microsome catalyzed irreversible binding of aflatoxin B 1 (AFB 1 ) to calf thymus DNA and up to a 5-fold increase in the ability to induce mutations in Salmonella typhimurium TA98. Maximum induction of AFB 1 binding to DNA occurred after 2 days of BHA administration whereas cytosolic glutathione S -transferase was maximally induced (6-fold) only after 10 days of BHA feeding. The induction of a new cytochrome P -450 species was indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and an enhanced sensitivity to inhibition by metyrapone and α-naphthoflavone. Addition of control cytosol (containing glutathione S -transferase) + glutathione to control microsomes decreased AFB 1 binding to DNA by 26%. However, replacement of control cytosol by BHA cytosol which contained 6 times more glutathione S -transferase only marginally enhanced the inhibition to 38%. These data suggest that BHA may exert its effect in the liver primarily through an alteration of the cytochrome P -450 dependent activation process although an increase in the conjugation of reactive metabolite may play a contributory role.
Rail Component Detection, Optimization, and Assessment for Automatic Rail Track Inspection

In this paper, we present a real-time automatic vision-based rail inspection system, which performs inspections at 16 km/h with a frame rate of 20 fps. The system robustly detects important rail components such as ties, tie plates, and anchors, with high accuracy and efficiency. To achieve this goal, we first develop a set of image and video analytics and then propose a novel global optimization framework to combine evidence from multiple cameras, Global Positioning System, and distance measurement instrument to further improve the detection performance. Moreover, as the anchor is an important type of rail fastener, we have thus advanced the effort to detect anchor exceptions, which includes assessing the anchor conditions at the tie level and identifying anchor pattern exceptions at the compliance level. Quantitative analysis performed on a large video data set captured with different track and lighting conditions, as well as on a real-time field test, has demonstrated very encouraging performance on both rail component detection and anchor exception detection. Specifically, an average of 94.67% precision and 93% recall rate has been achieved for detecting all three rail components, and a 100% detection rate is achieved for compliance-level anchor exception with three false positives per hour. To our best knowledge, our system is the first to address and solve both component and exception detection problems in this rail inspection area.
Upregulation of metabotropic glutamate receptor 8 mRNA expression in the rat forebrain after repeated amphetamine administration

Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors and are densely expressed in the forebrain of adult rats. Accumulative evidence suggests a critical role of mGluRs in the regulation of normal physiological activity of neurons and pathogenesis of mental illnesses such as schizophrenia, depression, and substance addiction. In this study, we investigated alterations in mGluR8 subtype mRNA expression in the rat forebrain in response to repeated intraperitoneal administration of amphetamine (twice daily for 12 days, 5 mg/kg per injection) using quantitative in situ hybridization. We found that mGluR8 mRNA levels were profoundly increased in the dorsal (caudate putamen) and ventral (nucleus accumbens) striatum 1 day after the discontinuation of amphetamine treatments. Such increases were sustained up to 21 days of withdrawal. Increases in mGluR8 mRNAs were also found in the cerebral cortex, including the cingulate and sensory cortex but not the piriform cortex, at 1 and 21 days. These data demonstrate a positive response of mGluR8 in mRNA abundance in most forebrain regions to repeated stimulant exposure.
Predictive modeling of laser hardening of AISI5150H steels

Abstract This paper presents accurate predictive modeling of the laser hardening process in terms of laser operating parameters and initial microstructure without the need of any experimental data. The model provides the diagrams that are useful for predicting hardness profiles, optimizing practical process parameters and assessing the potential of laser hardening for different steels. It is shown that the hardness and depth of the hardened layer in hypoeutectoid steels (carbon wt% The model combines a three-dimensional transient numerical solution for a rotating cylinder undergoing laser heating by a translating laser beam with a kinetic model describing pearlite dissolution, carbon redistribution in austenite and subsequent transformation to martensite by utilizing the feedback from the CCT diagram. In order to validate the thermal model and assert the accuracy of temperature predictions the temperature was measured using an infrared camera and a good agreement between the predicted and measured temperatures is shown. Results are presented as processing maps, which show how the case depth and hardness depend on input operating parameters. The good agreement between the measured and predicted hardness profiles ascertains the accuracy of the thermal-kinetic model developed for AISI5150H steels.
The improvement of cryogenic mechanical properties of Fe-12 Mn and Fe-8 Mn alloy steels through thermal/mechanical treatments

An investigation has been made to improve the low temperature mechanical properties of Fe-8Mn and Fe-12Mn-0.2 Ti alloy steels. A reversion annealing heat treatment in the two-phase (α+ γ) region following cold working has been identified as an effective treatment. In an Fe-12Mn-0.2Ti alloy a promising combination of low temperature (-196°C) fracture toughness and yield strength was obtained by this method. The improvement of properties was attributed to the refinement of grain size and to the introduction of a uniform distribution of retained austenite (γ). It was also shown that an Fe-8Mn steel could be grain-refined by a purely thermal treatment because of its dislocated α martensitic structure and absence of e martensite. As a result, a significant reduction of ductile to brittle transition temperature was obtained.
The dose of aspirin for the prevention of cardiovascular and cerebrovascular events.

ABSTRACTBackground: Low dose aspirin (ASA) (75–325 mg daily) is commonly used for the secondary prevention of cardiovascular and cerebrovascular events, as recommended by US national guidelines. Questions remain, however, as to whether there is a difference in the efficacy and safety across this low dose range.Scope: Double-blind controlled studies, meta-analyses, and observational analyses were reviewed to assess the body of evidence regarding the safety and efficacy of aspirin dosing.Findings: Only one double-blind study directly compared two doses of aspirin within the recommended low dose range. No difference in efficacy or safety was observed, although there was a trend toward greater efficacy with ASA 325 mg vs. ASA 81 mg. Three meta-analyses did not find a difference in bleeding events within the low dose range, while one found that higher doses were associated with more events. One meta-analysis found ASA 75–150 mg was as effective as ASA 160–325 mg. Observational analyses of low dose (75–325 mg) ...
A systematic approach to identifying and modeling the source of pharmacokinetic (PK) non-linearity

Purpose To develop a systematic approach to identify and model the source of nonlinearity, detected as non-constant AUC/dose and Cmax/dose ratios, observed in PK analyses of ascending dose exposures (6–100 mg) of talampanel, an innovative antiepileptic drug. Methods: Graphical evaluations of partial-AUC/dose ratios from a 4-arm single dose-escalation PK study (n=24), were followed by population PK analyses (NONMEM) using model discrimination criteria to identify the likely source of nonlinearity. Results: Graphical patterns of partial AUC/dose and Cmax/dose ratios revealed greatest non-linearity in the early post-dose time period, leading to the assumption that absorption is the most probable source of nonlinearity. Saturable first-pass bioavailability (F) was modeled as an asymptotic function of dose (F=Dose/(Kd+Dose). A parallel zero-/first-order absorption model coupled with a 1-compartment linear model adequately described the entire PK profile of talampanel. Kd (dose yielding 50% F) was 4.7 mg (intersubject variability of F=77%). A similar model was evaluated using Michaelis-Menten elimination, but was rejected due to a Km estimate 4–5 times higher than the highest Cmax, and little improvement of model fitting criteria (decreased objective function value, diagnostic plots). Conclusion: Graphical analyses of dose normalized AUC and Cmax values, coupled with population PK model testing can be used to identify and model the source of nonlinearity observed in PK analysis. Clinical Pharmacology & Therapeutics (2004) 75, P90–P90; doi: 10.1016/j.clpt.2003.11.346
The interpersonal nature of self-esteem: Do different measures of self-esteem possess similar interpersonal content?

The present study examined the interpersonal content of various self-esteem instruments in order to determine the interpersonal similarity of these measures. This was accomplished by measuring selfesteem and interpersonal style across seven samples (N = 1422). Each of the self-esteem instruments possessed significant interpersonal content and demonstrated interpersonal cohesion to the extent that all of the measures were located in either the Assured-Dominant or Gregarious-Extraverted regions of the interpersonal circumplex. These findings suggest that the self-esteem instruments included in the present study possess similar interpersonal content but that differences between these measures may exert subtle influences on how self-esteem is conceptualized in interpersonal contexts. Implications for the measurement and conceptualization of self-esteem will be discussed.
HOUSEHOLD RISK FACTORS FOR TRYPANOSOMA CRUZI SEROPOSITIVITY IN TWO GEOGRAPHIC REGIONS OF ECUADOR

Few studies on the relationship between environmental factors and Trypanosoma cruzi transmission have been conducted in Ecuador. We conducted a cross-sectional study of household risk factors for T. cruzi seropositivity in 2 distinct geographical regions of Ecuador. Exposure information was collected via household surveys, and subjects were tested for serological evidence of T. cruzi infection. In total, 3,286 subjects from 997 households were included. In the coastal region, factors associated with seropositivity were living in a house with a palm roof (odds ratio [OR] = 2.63, 95% confidence interval, [1.61, 4.27]), wood walls (OR = 5.75 [2.04, 16.18]), or cane walls (OR = 2.81 [1.31, 6.04]), and the presence of firewood in the peridomicile (OR = 2.48 [1.54, 4.01]). Accumulation of trash outside the home was associated with a reduced risk of seropositivity (OR = 0.25 [0.12, 0.51]). In the Andean region, living in a house with adobe walls was the only factor predictive of T. cruzi seropositivity. In concl...
STUDIES OF SPERMATOGENESIS IN THE HEPATICAE : III. Continuity between Plasma Membrane and Nuclear Envelope in Androgonial Cells of Blasia

An ultrastructural study of late-stage androgonial cells of Blasia pusilla, a thallose liverwort, showed the nearly spherical nuclei often lying close or appressed to the cell walls. In some cells the two membranes comprising the nuclear envelope separated, the inner membrane continuing intact as a limiting boundary of the nucleus and the membrane on the outer, cytoplasmic side recurving away from the nucleus to continue without evident interruption around the periphery of the cell as the plasma membrane. It is believed that Blasia offers the first completely convincing demonstration of the heretofore problematic continuity of cytoplasmic membranes. A possible sequence of events leading to this unusual relationship between nucleus and cytoplasm is suggested. The sequence includes blebbing of the outer membrane of the nuclear envelope and subsequent membrane proliferation, apparent isolation of cytoplasmic ground substance, fusion of internal membrane with the ectoplast, and migration that finally brings the nucleus into flat contact with the wall. While this manifestation of membrane continuity may be anomalous, it is not presently considered the result of cell injury.
Clinicopathological analysis of primary epithelial appendiceal neoplasms.

Appendiceal carcinomas are classified into three distinct histopathological disease entities: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), or peritoneal mucinous carcinomatosis with intermediate or discorant features (PMCA I/D). The treatment of appendiceal tumors should be based on accurate histopathological classification, per previously reported case series. The objective of this study was to evaluate the clinicopathologic presentation and outcome of patients with appendiceal tumors treated at our institution over a 15-year period. We identified patients with appendiceal tumors diagnosed or treated at our institution from January 1989 through May 2004. Chart review for age, gender, signs and symptoms at diagnosis, and treatment was performed. Review of the pathologic specimens was performed and tumors were classified as DPAM, PMCA I/D, or PMCA. Forty patients were identified (median age 52.5 years; males 38%). The number of patients with DPAM, PMCA I/D, and PMCA was 15 (38%), 6 (15%), and 18 (46%), respectively. Peritoneal involvement was seen in 11 (73%) of patients with DPAM, 5 (83%) of PMCA I/D, and 11 (61%) of PMCA. The median survival for patients with DPAM, PMCA I/D, and PMCA was 7.7 years (90% CI: 2.9—upper limit not estimable), 1.2 years (90% CI: 0.9–1.6), and 0.7 years (90% CI: 0.4–1.5), respectively. The difference in survival across the three groups was statistically significant. Three distinct histopathological disease entities exist in appendiceal tumors. The prognosis and management of these tumors should be based on the extent of disease and pathologic diagnosis.
A time dependent performance model for multihop wireless networks with CBR traffic

In this paper, we develop a performance modeling technique for analyzing the time varying network layer queueing behavior of multihop wireless networks with constant bit rate traffic. Our approach is a hybrid of fluid flow queueing modeling and a time varying connectivity matrix. Network queues are modeled using fluid-flow based differential equation models which are solved using numerical methods, while node mobility is modeled using deterministic or stochastic modeling of adjacency matrix elements. Numerical and simulation experiments show that the new approach can provide reasonably accurate results with significant improvements in the computation time compared to standard simulation tools.
Src Regulates Sphingosine-1-Phosphate Mediated Smooth Muscle Cell Migration

Background Sphingosine-1-phosphate (S-1-P) is a bioactive sphingolipid released from activated platelets at sites of arterial injury that stimulates migration of smooth muscle cells (SMC). The kinase src is a significant focal point in transmembrane signaling. This study examines the role of src during smooth muscle cell migration in response to S-1-P. Methods Human coronary arterial SMCs were cultured in vitro . Boyden microchemotaxis assays of migration were performed in response to S-1-P in the presence and absence the src inhibitor (PP2, 10 μM) and a dominant negative src construct (DNsrc). siRNA to S-1-P receptors was used to down-regulate the S-1-P receptors. Western blotting was performed for src and MAPK phosphorylation. Results Inhibition of src with PP2 but not PP3 partially blocked S-1-P-mediated cell migration. S-1-P induced time-dependent activation of src, which was inhibited by PP2 and adenoviral DNsrc. PP3 or an empty vector had no effect. Activation of src by S-1-P was inhibited by siRNA to S-1-PR1 and S-1-PR3 but not by S-1-PR2. When the VSMC were transfected with adenovirus containing βARK CT , an inhibitor to Gβγ, src activation was significantly attenuated. Src inhibition with PP2 reduced p38 MAPK and JNK activation but did not alter ERK1/2 activation. Conclusion S-1-P mediated VSMC migration is modulated by a G-protein-coupled src pathway partially through src-mediated p38 MAPK and JNK signaling and requires S-1-PR1 and S-1-PR3 receptors.
Clinical correlates and familial aggregation of age at onset in bipolar disorder.

OBJECTIVE: To assess whether age at onset variation reflects underlying genetic heterogeneity in bipolar disorder, the authors examined the clinical and familial characteristics of age at onset in bipolar disorder subjects from families with multiple affected members. METHOD: A total of 211 families with 1,856 subjects were ascertained through bipolar I disorder probands. All the subjects were assessed with the Diagnostic Interview for Genetic Studies and assigned diagnoses by trained clinicians using best estimate procedures. Admixture analysis with the 211 bipolar disorder probands was used to decompose the age-at-onset distribution into a mixture of theoretical normal distributions. Logistic regression with general estimating equations was then used to examine clinical correlates and familial aggregation of age at onset in all 717 bipolar disorder subjects. RESULTS: The age-at-onset distribution consisted of a mixture of three normal distributions with means of 16.6 (SD=5.1), 26.0 (SD=1.4), and 34.7 (S...
Generalized Analytical Solution and Study of Conductive Ellipsoidal Field Emitters

This paper presents new equations that describe ellipsoidal field emitters in both ellipsoidal and Cartesian coordinates. Expressions are found for the potential, electric field, and field enhancement at any point in space. For both ellipsoidal and spheroidal emitters, equations are given to determine field emission current density and total current. It is also shown that the field enhancement at the surface of a spheroidal emitter is purely dependent on the surface location and the emitter's height to radius aspect ratio. Furthermore, simplified equations are given to approximate the field enhancement and total current for prolate spheroidal emitters of height to radius ratios greater than 100.
Entity Extraction is a Boring Solved Problem---Or is it?

This paper presents empirical results that contradict the prevailing opinion that entity extraction is a boring solved problem. In particular, we consider data sets that resemble familiar MUC/ACE data, and report surprisingly poor performance for both commercial and research systems. We then give an error analysis that suggests research challenges for entity extraction that are neither boring nor solved.