cssi/SciSciGPT-SciSciNet huggingface dataset:
New perspectives on the theory of permeability and resistance in the study of drug transport and absorption

Permeability coefficient (P) expressed as distance per unit time has been commonly interpreted to represent the velocity of drug movement across a heterogeneous medium such as skin and intestinal epithelium. The basis of such an interpretation is questioned on several grounds. For example, the basic assumption for calculating P (as defined conventionally) according to the Fick's law of diffusion requires the entire medium to be homogeneous and rate-limiting in transport. The theoretical basis of the widely used total resistance or resistance additivity concept is reviewed. Such a concept is shown to be applicable to the study of total transit time across the medium but may not be applicable to the study of steady-state flux or absorption across the medium under normal conditions. Based on the diffusional, compartmental, absorptive clearance or carrier-mediated-transport analysis it is shown that only the first transport resistance from the bulk medium across the surface (such as cellular membranes) of the permeation medium (such as a cell or a tissue) is usually the deciding factor in drug transport or absorption. Resistances on the other side of the surface barrier usually only affect the drug accumulation vs. time profile in the medium, but not the steady-state flux or absorption. The role of unstirred water layer adjacent to the internal capillary wall is postulated to play an important role in causing the blood-flow dependency in absorption, a phenomenon that cannot be rationalized by the conventional effective permeability concept. The conventional concept of sink conditions on the serosal side is questioned. The present analysis further supports the use of the absorptive or transport clearance concept in absorption or transport study. Effective permeability is regarded as a mathematical operator for transport across a barrier or a tissue, and may be unrelated to the Fick's law of diffusion under most conditions. The velocity unit for P is regarded simply as a "collapsed" unit based on the absorptive or transport clearance per unit gross surface area. It is hoped that this commentary will stimulate further research and discussions in this general area of drug transport and absorption. It appears that there is a need to experimentally confirm the total resistance theory in biological systems.
WARM AND FUZZY: TEMPERATURE AND DENSITY ANALYSIS OF AN Fe XV EUV IMAGING SPECTROMETER LOOP

The Hinode EUV Imaging Spectrometer (EIS) and X-Ray Telescope (XRT) were designed in part to work together. They have the same spatial resolution and cover different but overlapping coronal temperature ranges. These properties make a combined data set ideal for multithermal analysis, where EIS provides the best information on the cooler corona (log T 6.5). Here, we analyze a warm non-flaring loop detected in images made in a strong EIS Fe XV emission line with a wavelength of 284.16 A and peak formation temperature of log T = 6.3. We perform differential emission measure (DEM) analysis in three pixels at different heights above the footpoint and find multithermal results with the bulk of the emission measure in the range 6.0 7.2); analysis with XRT data alone resulted in a DEM that was missing most of the cooler emission measure required to produce many of the EIS lines. Thus, both results were misleading and unphysical. It was only by combiningmore » the EIS and XRT data that we were able to produce a reasonable result, one without ad hoc assumptions on the shape and range of the DEM itself.« less
Possible association of the exetended MHC haplotype B44-SC30-DR4 with autism

We previously reported that the complement C4B null allele appears to be associated with infantile autism. Since the C4B null allele is known to be part of the extended or ancestral haplotype [B44-SC30-Dr4], we investigated the incidence of [B44-Sc30-DR4] in 21 autistic children and their parents. This extended haplotype was increased by almost six-fold in the autistic subjects as compared with healthy controls. Moreover, the total number of extended haplotypes expressed on chromosomes of autistic subjects was significantly increased as compared with those expressed on chromosomes of healthy subjects. We conclude that a gene related to, or included in, the extended major histocompatibility complex may be associated with autism.
Housing conditions of low‐income families in the private, unassisted housing market in the United states

Abstract The housing conditions of low‐income Americans, particularly those in or near poverty, have been documented in several government and private reports, as well as academic articles. These studies have either ignored or given scant attention to the differences in housing conditions between those families who receive various forms of public assistance and those who do not. Although most welfare programmes are provided as entitlements to those eligible, housing assistance is provided to only a few households who qualify — about one‐in‐four. The remaining households find their housing in the private, unassisted market. Little is known about the housing conditions of poor families who do not receive housing assistance, not to mention those who receive no public assistance. Asserting a serious scarcity of minimal standard housing units which are affordable to the poor, previous studies suggest that those not receiving housing assistance face virtually insurmountable obstacles to physically and financial...
MINIMUM INDUCED LOSS WINDMILLS AND PROPELLERS

Abstract Horizontal axis wind turbines can be designed advantageously to utilize minimum induced loss radial loading, exactly inverse to that of high efficiency airplane propellers, as described by Betz, Prandtl, (1919) and Goldstein (1929). Benefits include reduced tower load and increased wind energy for windmills downstream in an array. At M.I.T. the authors have developed a rotor design and analysis code, HELICE, which exploits analytic simplications possible with near minimum induced loss loading. Earlier versions have been used to design propellers for human powered airplanes (1979) and windmills (1980). Algorithms and exmples are given.
Diffusion of radiation patterns due to scattering by random inhomogeneities

Abstract A ray acoustic treatment suggested previously by Chernov and Lighthill is applied to the problem of estimating the alteration of directivity patterns due to random inhomogeneities in the medium in which the patterns propagate. The pattern is assumed to evolve from a basic pattern taken from Gutin type formulae which solve for the directivity in a homogeneous, uniform medium. As shown by Chernov and Lighthill, the expected value of the directivity pattern may be computed in terms of a probability distribution function which obeys a diffusion equation. Some calculations are presented of such diffusion as a function of spinning mode lobe number, the wavenumber of the waves, the mean radius at which the lobe is generated, the drag-to-thrust ratio of the dipole source generating the mode, the diffusion constant associated with the inhomogeneity and the radius of measurement of the directivity pattern. Estimates are presented of the diffusion constant likely when the source of inhomogeneity is turbulent motion of the medium.
Divergent Evolution of Human p53 Binding Sites: Cell Cycle Versus Apoptosis

The p53 tumor suppressor is a sequence-specific pleiotropic transcription factor that coordinates cellular responses to DNA damage and stress, initiating cell-cycle arrest or triggering apoptosis. Although the human p53 binding site sequence (or response element [RE]) is well characterized, some genes have consensus-poor REs that are nevertheless both necessary and sufficient for transactivation by p53. Identification of new functional gene regulatory elements under these conditions is problematic, and evolutionary conservation is often employed. We evaluated the comparative genomics approach for assessing evolutionary conservation of putative binding sites by examining conservation of 83 experimentally validated human p53 REs against mouse, rat, rabbit, and dog genomes and detected pronounced conservation differences among p53 REs and p53-regulated pathways. Bona fide NRF2 (nuclear factor [erythroid-derived 2]-like 2 nuclear factor) and NFκB (nuclear factor of kappa light chain gene enhancer in B cells) binding sites, which direct oxidative stress and innate immunity responses, were used as controls, and both exhibited high interspecific conservation. Surprisingly, the average p53 RE was not significantly more conserved than background genomic sequence, and p53 REs in apoptosis genes as a group showed very little conservation. The common bioinformatics practice of filtering RE predictions by 80% rodent sequence identity would not only give a false positive rate of ∼19%, but miss up to 57% of true p53 REs. Examination of interspecific DNA base substitutions as a function of position in the p53 consensus sequence reveals an unexpected excess of diversity in apoptosis-regulating REs versus cell-cycle controlling REs (rodent comparisons: p < 1.0 e−12). While some p53 REs show relatively high levels of conservation, REs in many genes such as BAX, FAS, PCNA, CASP6, SIVA1, and P53AIP1 show little if any homology to rodent sequences. This difference suggests that among mammalian species, evolutionary conservation differs among p53 REs, with some having ancient ancestry and others of more recent origin. Overall our results reveal divergent evolutionary pressure among the binding targets of p53 and emphasize that comparative genomics methods must be used judiciously and tailored to the evolutionary history of the targeted functional regulatory regions.
ORNL biometric eye model for iris recognition

Iris recognition has been proven to be an accurate and reliable biometric. However, the recognition of non-ideal iris images such as off angle images is still an unsolved problem. We propose a new biometric targeted eye model and a method to reconstruct the off-axis eye to its frontal view allowing for recognition using existing methods and algorithms. This allows for existing enterprise level algorithms and approaches to be largely unmodified by using our work as a pre-processor to improve performance. In addition, we describe the ‘Limbus effect’ and its importance for an accurate segmentation of off-axis irides. Our method uses an anatomically accurate human eye model and ray-tracing techniques to compute a transformation function, which reconstructs the iris to its frontal, non-refracted state. Then, the same eye model is used to render a frontal view of the reconstructed iris. The proposed method is fully described and results from synthetic data are shown to establish an upper limit on performance improvement and establish the importance of the proposed approach over traditional linear elliptical unwrapping methods. Our results with synthetic data demonstrate the ability to perform an accurate iris recognition with an image taken as much as 70 degrees off-axis.
Altered subcellular localization of transcription factor TEAD4 regulates first mammalian cell lineage commitment

In the preimplantation mouse embryo, TEAD4 is critical to establishing the trophectoderm (TE)-specific transcriptional program and segregating TE from the inner cell mass (ICM). However, TEAD4 is expressed in the TE and the ICM. Thus, differential function of TEAD4 rather than expression itself regulates specification of the first two cell lineages. We used ChIP sequencing to define genomewide TEAD4 target genes and asked how transcription of TEAD4 target genes is specifically maintained in the TE. Our analyses revealed an evolutionarily conserved mechanism, in which lack of nuclear localization of TEAD4 impairs the TE-specific transcriptional program in inner blastomeres, thereby allowing their maturation toward the ICM lineage. Restoration of TEAD4 nuclear localization maintains the TE-specific transcriptional program in the inner blastomeres and prevents segregation of the TE and ICM lineages and blastocyst formation. We propose that altered subcellular localization of TEAD4 in blastomeres dictates first mammalian cell fate specification.
Fluid–Structure Interaction Modeling of Vertical-Axis Wind Turbines

Full-scale, 3D, time-dependent aerodynamics and fluid‐structure interaction (FSI) simulations of a Darrieus-type vertical-axis wind turbine (VAWT) are presented. A structural model of the Windspire VAWT (Windspire energy, http://www.windspireenergy.com/ )i s developed, which makes use of the recently proposed rotation-free Kirchhoff‐Love shell and beam/cable formulations. A moving-domain finite-element-based ALE-VMS (arbitrary Lagrangian‐Eulerian-variational-multiscale) formulation is employed for the aerodynamics in combination with the sliding-interface formulation to handle the VAWT mechanical components in relative motion. The sliding-interface formulation is augmented to handle nonstationary cylindrical sliding interfaces, which are needed for the FSI modeling of VAWTs. The computational results presented show good agreement with the field-test data. Additionally, several scenarios are considered to investigate the transient VAWT response and the issues related to self-starting. [DOI: 10.1115/1.4027466]
The use of tannic acid for the ultrastructural visualization of hyaluronic acid.

This study describes a method, which makes use of tannic acid (2%) as a component of a paraformaldehyde-glutaraldehyde based fixative, to reveal the presence and ultrastructure of glycosaminoglycans in the extracellular matrix. The ultrastructure of the extracellular matrix in the stage 24 chick embryo wing is examined after fixation by several procedures. After fixation in the absence of tannic acid, the intercellular spaces contain little extracellular matrix, except for occasional fibrils (collagen?). On the other hand, when tannic acid is included in the primary fixative, the intercellular spaces contain considerable amounts extracellular matrix which includes 3±0.5 nm filaments, ±30 nm granules, as well as putative collagen fibrils. The 3±0.5 nm diameter fibrils are not observed when the limbs had been injected in ovo with Streptomyces hyaluronidase (specific for hyaluronic acid) prior to fixation. Furthermore, the 3±0.5 nm fibrils resemble authentic hyaluronic acid that had been fixed by the same procedure in the presence of tannic acid. Limbs treated with tannic acid after osmication contained only small amounts of extracellular material, which was confined largely to cell surfaces. These results demonstrate that the use of tannic acid in the primary fixative can serve as a useful method for the ultrastructural visualization of several extracellular matrix materials, including hyaluronic acid.
Iron Accumulation in Bronchial Epithelial Cells is Dependent on Concurrent Sodium Transport

Airway epithelial cells prevent damaging effects of extracellular iron by taking up the metal and sequestering it within intracellular ferritin. Epithelial iron transport is associated with transcellular movement of other cations including changes in the expression or activity of Na, K-ATPase and epithelial Na(+) channel (ENaC). Given this relationship between iron and Na(+), we hypothesized that iron uptake by airway epithelial cells requires concurrent Na(+) transport. In preliminary studies, we found that Na(+)-free buffer blocked iron uptake by human airway epithelial cell. Na(+) channels inhibitors, including furosemide, bumetanide, and ethylisopropyl amiloride (EIPA) significantly decreased epithelial cell concentrations of non-heme iron suggesting that Na(+)-dependent iron accumulation involves generalized Na(+) flux into the cells rather than participation of one or more specific Na(+) channels. In addition, efflux of K(+) was detected during iron uptake, as was the influx of phosphate to balance the inward movement of cations. Together, these data demonstrate that intracellular iron accumulation by airway epithelium requires concurrent Na(+)/K(+)exchange.
Online Social Networks and Insights into Marketing Communications

Even though online social network services have become enormously popular among general public, there is a laxity of empirical investigations on the individual's level in this domain. This paper examines the impact of personality factors such as extraversion, self-esteem, opinion seeking and opinion leadership on brand communication and online social behaviors. Our results show that gender and extroversion predict online social network size and time spent online; that opinion seekers spend more time online and have larger networks relative to opinion leaders; and that opinion leaders are more likely to communicate their brand use online. We also find the mediating role of opinion leadership and opinion seeking in explaining the impact of general personality traits on online brand communication and social networking. Directions for future research are provided and some practical implications are discussed.
IONIZATION LAYERS OBSERVED AT MIDDLE LATITUDES BY ATMOSPHERE EXPLORER-C

Abstract In the early phases of the Atmosphere Explorer mission the highly elliptical orbit with apogee near 4000 km and perigee near 135 km, allowed altitude profiles of the ion composition to be obtained over limited latitude extents at middle latitudes. Data from consecutive orbits through the mid-latitude ionosphere show the repeated appearance of ionization layers that are distributed in longitude, appearing at the same geographic location but different geomagnetic locations. In this data set the layers appear at dip latitudes as high as 40° and at these locations the magnetic declination can be significant. Examination of the shape of these layers at different longitudes supports the idea that both meridional and zonal winds may play a role in the field-aligned plasma transport that is primarily responsible for their formation.
Effects of anonymity and experimenter demand on client satisfaction with mental health services.

Abstract Among the methodological issues associated with the measurement of client satisfaction are those concerning anonymity of response, experimenter demand effects, and reliability of instruments. In this study, 100 inpatients were randomly assigned in a 2 × 2 factorial design; subjects were asked or not asked to sign their names to the CSQ-8 questionnaire and were asked or not asked to “tell it like it is.” The reported satisfaction of those given anonymity was significantly lower but there was no effect due to demand. Furthermore, subjects in the anonymity group had lower scores on all 8 items of the questionnaire. A factor analysis of the CSQ-8 revealed one major factor; the internal consistency of the scale was .93. The CSQ-8 was found to be a useful measure of overall client satisfaction but, because ceiling effects are a pervasive problem in client satisfaction research, anonymity should be assured whenever possible.
Design and Application of a Nonlinear Energy Sink to Mitigate Vibrations of an Air Spring Supported Slab

In this paper we consider the application of a nonlinear energy sink (NES), a passive isolation device, to damp out energy from the low frequency modes of an air-spring supported slab to be installed at Purdue University’s Birck Nanotechnology Center. Analytical expressions to obtain energy sink design parameters, given some primary system specifications, have been derived. These expressions are then used to design the NES for the Birck air-spring supported slab. The designed NES is then analyzed via finite elements to study its efficacy in absorbing low frequency vibration from the slab. The study reveals that NES can serve as a good aid in dissipating vibrational energy induced by small disturbances in the slab.Copyright © 2005 by ASME
Emmert’s imaginal law

The apparent size of a visual afterimage increases in proportion with the distance at which that image is viewed; this is Emmert’s law. Contrary to Emmert’s law for afterimages, this paper reports that the apparent size of a mentally imaged object decreases monotonically with increases in the distance of the viewing surface.
The 9/11 effect: Toward a social science of the terrorist threat

Abstract After 9/11, public attitudes on numerous social issues changed. While many studies have examined post-9/11 attitude trends on specific topics, such as civil liberties or war, few have investigated the scope and variety of these effects. Did the events of 9/11 have a brief effect on a limited number of attitudes, or did they produce numerous, long-term changes in the way Americans think, feel and act? Drawing on a broad range of pre–post-9/11 studies, this review essay begins to answer this question by developing a framework for categorizing these effects and distinguishing short-term changes from long-term ones. The framework is intended to help facilitate an interdisciplinary social scientific research agenda on the effects of 9/11 and other terrorist acts. The essay concludes by explaining the social importance of the public's response to terrorism and the need for further research on this topic.
Molecular Recognition of the Palmitoylation Substrate Vac8 by Its Palmitoyltransferase Pfa3

Palmitoylation of the yeast vacuolar protein Vac8 is important for its role in membrane-mediated events such as vacuole fusion. It has been established both in vivo and in vitro that Vac8 is palmitoylated by the Asp-His-His-Cys (DHHC) protein Pfa3. However, the determinants of Vac8 critical for recognition by Pfa3 have yet to be elucidated. This is of particular importance because of the lack of a consensus sequence for palmitoylation. Here we show that Pfa3 was capable of palmitoylating each of the three N-terminal cysteines of Vac8 and that this reaction was most efficient when Vac8 is N-myristoylated. Additionally, when we analyzed the Src homology 4 (SH4) domain of Vac8 independent of the rest of the protein, palmitoylation by Pfa3 still occurred. However, the specificity of palmitoylation seen for the full-length protein was lost, and the SH4 domain was palmitoylated by all five of the yeast DHHC proteins tested. These data suggested that a region of the protein C-terminal to the SH4 domain was important for conferring specificity of palmitoylation. This was confirmed by use of a chimeric protein in which the SH4 domain of Vac8 was swapped for that of Meh1, another palmitoylated and N-myristoylated protein in yeast. In this case we saw specificity mimic that of wild type Vac8. Competition experiments revealed that the 11th armadillo repeat of Vac8 is an important element for recognition by Pfa3. This demonstrates that regions distant from the palmitoylated cysteines are important for recognition by DHHC proteins.
Der Kategorische Imperativ als Grundstein der Menschenwürde und Form der Offenbarung Gottes bei Immanuel Kant und Karol Wojtyla

The aim of this analysis is to show the categorical imperative as the cornerstone of human dignity and form of revelation of God in the work of Immanuel Kant and Karol Wojtyla. The suspicious and distant attitude of Christian philosophers, as well as the Catholic Church compared to Kant has a long history. To this day there are only a few researches that analyse from this point of view (Kantian influences) the philosophical thinking of Karol Wojtyla. Though Kant identified the question of God as the cardinal question of our abstract rationality, he believed in God and future life, even in his lifetime he was underestimated, misunderstood and treated with hostility. The experience of duty is”ratio conoscendi” of freedom in Kant and Wojtyla. For the two thinkers the question of freedom is the basic category of there philosophies. Through which authority moral law challenges the human being? Kant and Wojtyla, both philosophers comprehend the highest authority as divine power which formulated the moral law before man. The “holy lawmaker” – God – reveals himself in the human act.
Understanding the Molecular Basis of RNA Polymerase II Transcription

Synthetic nucleic acid analogues have profoundly advanced our knowledge of DNA and RNA, as well as the complex biological processes that involve nucleic acids. As a pivotal enzyme, eukaryotic RNA polymerase II (Pol II) is responsible for transcribing DNA into messenger RNA, which serves as a template to direct protein synthesis. Chemically modified nucleic acid analogues have greatly facilitated the structural elucidation of RNA Pol II elongation complex and understanding the key chemical interactions governing RNA Pol II transcriptional fidelity. This review addresses major progress in RNA polymerase II mechanistic studies using modified nucleic acid analogues in recent years.
Functional characterization of the genes of bacteriophage T1

Abstract Amber mutants representing the 18 known genes of coliphage T1 Michalke 1967 were examined for DNA synthesis, head or tail production, and cell lysis in a nonpermissive host. Mutants in genes 1 or 2 are nearly completely defective in phage DNA synthesis. However, they are still capable of rapidly shutting off host DNA synthesis. This shutoff is caused by a phage-induced protein, since it is inhibited by chloramphenicol. Gene 1 or gene 2 mutants also affect lysis kinetics of the infected cells to permit only a delayed and incomplete lysis. The gene 4 mutant causes a premature arrest of phage DNA synthesis, but lyses the host normally. Mutants in all other genes are normal in DNA synthesis and lysis, but are defective in some stage of maturation. An in vitro complementation assay and electron microscopy of lysates from the nonpermissive host were used to ascertain that the mutants of gene 3 and genes 5 to 11 inclusive are producers of heads, but not tails. Presumably, these genes are involved in tail biosynthesis. Conversely, gene 4 and genes 12 to 18 inclusive are involved in head biosynthesis because mutants in these genes produce only tails.
Negative magnetoresistance as a result of hopping conduction in polycrystalline thin films of beta -FeSi2.

Low-temperature negative magnetoresistance has been measured in polycrystalline thin films of semiconducting iron disilicide prepared by pulsed laser deposition. The onset of negative magnetoresistance occurs at a temperature of \ensuremath{\sim}20 K and increases with decreasing temperature. No saturation is observed in the magnetoresistance, which displays an ${\mathit{H}}^{2}$ behavior for magnetic-field values below 8 kOe, and an ${\mathit{H}}^{1/2}$ behavior for higher values through 55 kOe. Resistivity measurements indicate that hopping conduction becomes the transport mechanism below \ensuremath{\sim}200 K and is therefore assumed to be responsible for the negative magnetoresistance.
Field Experimentation of Cots-Based UAV Networking

Low-cost and high-performance Commercial Off-The-Shelf (COTS) wireless equipment, such as IEEE 802.11 wireless LAN ("Wi-Fi"), has so advanced that it is now practical to use it in small low-altitude Unmanned Aerial Vehicles (UAVs). This new capability has inspired many novel application ideas in UAV networking. We argue that field experimentation of UAV networking is essential in collecting link measurement data, developing network protocols and applications, and evaluating their performance in realistic environments, and that it is feasible to conduct these experiments cost-effectively with COTS-based equipment. We describe several ongoing field experiments and initial results. Lastly, we briefly describe future testing plans as well as suggest methods of facilitating rapid and inexpensive UAV networking field experimentation.
Interactive view-dependent rendering of large isosurfaces

We present an algorithm for interactively extracting and rendering isosurfaces of large volume datasets in a view-dependent fashion. A recursive tetrahedral mesh refinement scheme, based on longest edge bisection, is used to hierarchically decompose the data into a multiresolution structure. This data structure allows fast extraction of arbitrary isosurfaces to within user specified view-dependent error bounds. A data layout scheme based on hierarchical space filling curves provides access to the data in a cache coherent manner that follows the data access pattern indicated by the mesh refinement.
Simian Virus 40 Large T Antigen Induces IFN-Stimulated Genes through ATR Kinase

Polyomaviruses encode a large T Ag (LT), a multifunctional protein essential for the regulation of both viral and host cell gene expression and productive viral infection. Previously, we have shown that stable expression of LT protein results in upregulation of genes involved in the IFN induction and signaling pathway. In this study, we focus on the cellular signaling mechanism that leads to the induction of IFN responses by LT. Our results show that ectopic expression of SV40 LT results in the induction of IFN-stimulated genes (ISGs) in human fibroblasts and confers an antiviral state. We describe a LT-initiated DNA damage response (DDR) that activates IFN regulatory factor 1, causing IFN-β production and consequent ISG expression in human cells. This IFN-β and ISG induction is dependent on ataxia-telangiectasia mutated and Rad3-related (ATR) kinase, but independent of ATM. ATR kinase inhibition using a selective kinase inhibitor (ETP-46464) caused a decrease in IFN regulatory factor 1 stabilization and ISG expression. Furthermore, expression of a mutant LT that does not induce DDR also does not induce IFN-β and ISGs. These results show that, in the absence of viral infection, LT-initiated activation of ATR-dependent DDR is sufficient for the induction of an IFN-β–mediated innate immune response in human cells. Thus, we have uncovered a novel and critical role for ATR as a mediator of antiviral responses utilizing LT.
Multiple time level adjustment for data assimilation

Time-stepping schemes in ocean–atmosphere models can involve multiple time levels. Traditional data assimilation implementation considers only the adjustment of the current state using observations available, i.e. the one time level adjustment. However, one time level adjustment introduces an inconsistency between the adjusted and unadjusted states into the model time integration, which can produce extra assimilation errors. For time-dependent assimilation approaches such as ensemble-based filtering algorithms, the persistent introduction of this inconsistency can give rise to computational instability and requires extra time filtering to maintain the assimilation. A multiple time level adjustment assimilation scheme is thus proposed, in which the states at times t and t − 1, t − 2, . . . , if applicable, are adjusted using observations at time t. Given a leap frog time-stepping scheme, a low-order (Lorenz-63) model and a simple atmospheric (global barotropic) model are used to demonstrate the impact of the two time level adjustment on assimilation results in a perfect model framework with observing/assimilation simulation experiments. The assimilation algorithms include an ensemble-based filter (the ensemble adjustment Kalman filter, EAKF) and a strong constraint four-dimensional variational (4D-Var) assimilation method. Results show that the two time level adjustment always reduces the assimilation errors for both filtering and variational algorithms due to the consistency of the adjusted states at times t and t − 1 that are used to produce the future state in the leap frog timestepping. The magnitude of the error reduction made by the two time level adjustment varies according to the availability of observations, the nonlinearity of the assimilation model and the strength of the time filter used in the model. Generally the sparser the observations in time, the larger the error reduction. In particular, for the EAKF when the model uses a weak time filter and for the 4D-Var method when the model is strongly nonlinear, two time level adjustment can significantly improve the performance of these assimilation algorithms.
A Measure of Paradigm Beliefs About the Social World

This study examined the reliability and construct validity of, along with age differences in, a measure of paradigm beliefs about the social world, beliefs that have been proposed to develop across the adolescent and adult life span. The scale is a 27-item, forced-choice preference measure of absolute, relativistic, and dialectical paradigm beliefs. In a series of investigations with 445 subjects, ranging in age from 16 to 83 years, it was shown to have good internal consistency and test-retest reliability, and both convergent and discriminant validities. It predicted performance on an in-depth interview about paradigm beliefs and was related to two other measures of paradigm beliefs. It was not related to selected personality variables (i.e., social dogmatism, intolerance of ambiguity and social desirability); nor was it related to a measure of verbal intelligence. The scale also showed predicted developmental trends, supporting its utility for developmental research.
Dumje: paradox and resolution in Sherpa ritual symbolism

Ritual may be usefully viewed as a symbolic attempt to resolve contradictory ideas and affects within a single cultural tradition. One such paradox faced by Buddhism in practice is the necessity of simultaneously affirming and denying the value of worldly existence. The Sherpa seasonal festival of Dumje may be understood as an attempt periodically to express and resolve this problem through a complex juxtaposition of sexual, aggressive, and ecological metaphors and symbols.
“I’ll Have What He’s Having”: Group Ordering Behavior in Food Choice Decisions

Current research has focused on whether nutrition labeling and pricing policies (e.g., soda taxes) influence food decisions; however, less attention has been given to how peers influence one’s food decisions. This study uses sales receipts from a full-service restaurant to take a closer look at how people order in groups. Results of the study revealed people may be less variety-seeking than previous research suggests; in fact, diners were more likely to seek variety when choosing an individual item, but not when choosing a menu category. In other words, diners wanted to be different from their dining companions, but not too different. This result was further confirmed with a model of food choice which shows diners derived more utility from an entree when a fellow diner ordered an entree in the same category. Interestingly, the presence of calorie labels on menus did not change the marginal utility of calories, suggesting peer effects may outweigh the effects of nutritional information.
Germination of Bacillus megaterium Spores After Various Extraction Procedures

The initiation of germination of Bacillus megaterium QM B1551 spores, grown in supplemented nutrient broth, has been studied. The initiation properties depend on buffer concentrations and the particular batch of spores. Initiation in l-alanine, KBr, calcium dipicolinate, or in buffer alone increases as a function of the spore age; whereas initiation in glucose, l-leucine, or l-proline remains relatively constant. Extraction of spores with alkali, sodium dodecyl sulfate-dithiothreitol, or lithium diiodosalicylate removes variable amounts of dipicolinic acid, hexosamine, and protein. These extracted spores are still capable of initiation and, in some cases, initiation is stimulated. However, extraction of spores with 8 M urea-10% mercaptoethanol inhibits subsequent initiation.
Therapeutic drug monitoring of psychoactive drugs during pregnancy in the genomic era: challenges and opportunities.

Various symptoms of mental illness occur commonly during pregnancy. It is estimated that serious mental disorders, including major depression, bipolar disorder, schizophrenia, panic and other anxiety disorders, occur with a frequency of 10 to 25% in community samples of US women in their child-bearing years. As a result, approximately a third of all women take at least one psychoactive drug during pregnancy. Fetal drug exposure has been documented for all psychoactive drugs studied to date. However, the rate and extent of placental transfer within and between psychoactive drug classes remains ill defined. The contribution of various genetic factors such as the role of polymorphic drug metabolizing enzymes and drug transporters in controlling the variability of fetal drug exposure is also unclear. Therapeutic drug monitoring (TDM) has traditionally played an important role in psychiatric pharmacotherapy during pregnancy to ensure an adequate drug dose to achieve desired benefits while avoiding excessive fe...
Analysis Methods in Time-Based Claims

Assessing the impact of delay and resolving disputes are contentious issues since courts and administrative boards do not specify standard delay analysis practices. First, the advantages and disadvantages of widely used delay analysis methods, including the as-planned versus as-built, impact as-planned, collapsed as-built, time impact, and productivity analysis methods are summarized. Fifty-eight claim cases associated with time-based disputes in government work during the 1992–2005 period are extracted and analyzed to observe issues in time-based claims, including the reasons why they occur and the common practices in their resolution. The effects of various factors on the selection of a delay analysis method are examined. These factors include the type of schedule used, the schedule updating practice, the use of existing versus newly created schedules, and the availability of expertise, information, time, and funds. A project management system that makes use of regularly updated network schedules, and t...
Noninvasive Imaging of Tumor Burden and Molecular Pathways in Mouse Models of Cancer

Imaging plays a central role in the diagnosis of cancer and the evaluation of therapeutic efficacy in patients with cancer. Because macroscopic imaging is noninvasive and quantitative, the development of specialized instruments for small animals has spurred increasing utilization in preclinical cancer studies. Some small-animal imaging devices are miniaturized derivatives of clinical imaging modalities, including computed tomography, magnetic resonance imaging, positron-emission tomography, single-photon emission computed tomography, and ultrasonography. Optical imaging, including bioluminescence imaging and fluorescence imaging, has evolved from microscopic cellular imaging technologies. Here, we review how current imaging modalities are enabling high-resolution structural imaging with micrometer-scale spatial resolution, thus allowing for the quantification of tumor burden in genetically engineered and orthotopic models of cancer, where tumors develop within organs not typically accessible to measurements with calipers. Beyond measuring tumor size, imaging is increasingly being used to assess the activity of molecular pathways within tumors and to reveal the pharmacodynamic efficacy of targeted therapies. Each imaging technology has particular strengths and limitations, and we discuss how studies should be carefully designed to match the imaging approach to the primary experimental question.
Software requirements and support for image-algebraic analysis, detection, and recognition of small targets

The detection of hazardous targets frequently requires a multispectral approach to image acquisition and analysis, which we have implemented in a software system called MATRE (multispectral automated target recognition and enhancement). MATRE provides capabilities of image enhancement, image database management, spectral signature extraction and visualization, statistical analysis of greyscale imagery, as well as 2D and 3D image processing operations. Our system is based upon a client-server architecture that is amenable to distributed implementation. In this paper, we discuss salient issues and requirements for multispectral recognition of hazardous targets, and show that our software fulfills or exceeds such requirements. MATRE's capabilities, as well as statistical and morphological analysis results, are exemplified with emphasis upon computational cost, ease of installation, and maintenance on various Unix platforms. Additionally, MATRE's image processing functions can be coded in vector-parallel form, for ease of implementation of SIMD-parallel processors. Our algorithms are expressed in terms of image algebra, a concise, rigorous notation that unifies linear and nonlinear mathematics in the image domain. An image algebra class library for the C + + language has been incorporated into the our system, which facilitates fast algorithm prototyping without the numerous drawbacks of descrete coding.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Pitting Corrosion of Bare Stainless Steel 304 under Chloride Solution Droplets

Pitting corrosion behavior of stainless steel 304 (SS304) under droplets of chloride solution was investigated using a Kelvin probe (KP). Droplets of different volumes of MgCl 2 solution were placed on the steel surface and exposed to a constant low relative humidity (RH). As the concentration increased during the exposure of the drop to low RH, the open-circuit potential (OCP) and the shape change of the drop were monitored by the KP. Pit initiation was detected by a sudden decrease in the OCP. Pits initiated earlier under small droplets than under large drops. The chloride concentration at initiation was between 3.0 and 8.4 M for droplets with a starting concentration of 0.88 M Cl ― . The initiation concentration increased when the initial concentration of the droplet was higher. The anodic current demand of pits growing at the OCP decreased with time as did the available cathodic current. When the current demand exceeded the available cathodic current, the active pit area decreased. A mechanism for pit formation and growth under droplets of MgCl 2 solution was proposed.
Establishing and Sustaining System Integrity via Root of Trust Installation

Integrity measurements provide a means by which distributed systems can assess the trustability of potentially compromised remote hosts. However, current measurement techniques simply assert the identity of software, but provide no indication of the ongoing status of the system or its data. As a result, a number of significant vulnerabilities can result if the system is not configured and managed carefully. To improve the management of a system's integrity, we propose a Root of Trust Installation (ROTI) as a foundation for high integrity systems. A ROTI is a trusted system installer that also asserts the integrity of the trusted computing base software and data that it installs to enable straightforward, comprehensive integrity verification for a system. The ROTI addresses a historically limiting problem in integrity measurement: determining what constitutes a trusted system state in a heterogeneous, evolving environment. Using the ROTI, a high integrity system state is defined by its installer, thus enabling a remote party to verify integrity guarantees that approximate classical integrity models (e.g., Biba). In this paper, we examine what is necessary to prove the integrity of the trusted computing base (sCore) of a distributed security architecture, called the Shamon. We describe the design and implementation of our custom ROTI sCore installer and study the costs and effectiveness of binding system integrity to installation in the distributed Shamon. This demonstration shows that strong integrity guarantees can be efficiently achieved in large, diverse environments with limited administrative overhead.
Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage

Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
Differential Expression of Inflammatory Cytokines Parallels Progression of Central Nervous System Pathology in Two Clinically Distinct Models of Multiple Sclerosis

Multiple sclerosis is an immune-mediated demyelinating disease of unknown etiology that presents with either a chronic-progressive or relapsing-remitting clinical course. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) and relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) in the SJL/J mouse are both relevant murine CD4+ T cell-mediated demyelinating models that recapitulate the multiple sclerosis disease phenotypes. To determine the cellular and molecular basis for these observed differences in clinical course, we quantitatively analyzed the temporal expression of pro- and antiinflammatory cytokine mRNA expression in the central nervous system (CNS) and the phenotype of the inflammatory mononuclear infiltrates. TMEV-infected SJL/J mice expressed IFN-gamma, TNF-alpha, IL-10, and IL-4 mRNA during the preclinical phase, and their levels continued to increase throughout the duration of the chronic-progressive disease course. These data correlated with the continued presence of both CD4+ T cells and F4/80+ macrophages within the CNS infiltrates. In contrast, SJL/J mice with PLP(139-151)-induced R-EAE displayed a biphasic pattern of CNS expression for the proinflammatory cytokines, IFN-gamma and TNF-alpha, with expression peaking at the height of the acute phase and relapse(s). This pattern correlated with dynamic changes in the CD4+ T cell and F4/80+ macrophage populations during relapsing-remitting disease progression. Interestingly, IL-4 message was undetectable until disease remission(s), demonstrating its potential role in the intrinsic regulation of ongoing disease, whereas IL-10 was continuously expressed, arguing against a regulatory role in either disease. These data suggest that the kinetics of cytokine expression together with the nature of the persistent inflammatory infiltrates are major contributors to the differences in clinical course between TMEV-IDD and R-EAE.
On characterizing nilpotent lie algebras by their multipliers

In recent work, groups of order pj whose multiplier has order , have been classified when t(G) = 0 or 1 in [2] and when t(G) = 2 in [6]. It is the purpose of this paper to obtain similar results for Lie algebras.
Optical time and frequency standard based on single indium ion

We feel that continuing advancement of the state of the art of single ion trapping and laser technology will make a single laser-cooled ion a viable candidate for a time or frequency standard in the very near future. The recent achievements in flywheel laser technology and the use of femtosecond "comb" lasers to bridge the optical-microwave gap are very important steps in this direction. These advances together with the well-known advantages of,an optical frequency and small systematics should make the prospects for a single-ion optical standard very favorable indeed.