cssi/SciSciGPT-SciSciNet huggingface dataset:
Current status of the use of theophyllines in children.

Theophyllines have gone through cycles of popularity and unpopularity as therapeutic agents since they were first used for relief of asthma in 1936. By competitive inhibition of the enzyme phosphodiesterase, they prevent the breakdown of cyclic 39,59—AMP (adenosine monophosphate) to 59—AMP and act synergistically with beta-adrenergic agents to increase the intracellular concentration of 39 5 cyclic AMP. In lung tissue cyclic 39,59—AMP leads to relaxation of bronchial smooth muscle, perhaps by direct effect or perhaps by suppression of local histamine release.1 Theophyllines are of particular value in the epinephrine-resistant patient with asthma. Toxic effects of theophyllines are related to serum theophylline levels and represent intensifications of pharmacologic effects. They include insomnia, irritability, restlessness, tremors, convulsions, flushing, tachycardia and other cardiac arrhythmias, hypotension or hypertension, abdominal pain, anorexia, nausea, vomiting, hematemesis, dehydration, and albuminuria. Gastrointestinal side effects are centrally mediated and are not prevented or ameliorated by giving theophyllines rectally or intravenously.2 In the 19609s many physicians virtually discontinued the use of aminophylline, which is 80% theophylline by weight and hydrolyzed to free theophylline in vivo, because of numerous reports of deaths following its administration.3-6 Most of the childhood deaths attributable to this drug occurred after use of rectal suppositories.5,6 Absorption from the suppository base is slow and unpredictable,7 and cumulative effects often occur. Administration of excessive amounts of theophylline or aminophylline (or administration of the latter by rapid intravenous injection, injection into a central venous catheter,8 or administration to patients with compromised cardiovascular or renal systems3,4) has also been associated with deaths, more often in adults than in children. Idiosyncratic reactions are exceptionally rare.
Flux Pinning for In Situ Prepared Superconducting Composites

In situ superconducting composites1–3 differ from bronze process4, 5 Nb3Sn-Cu multifilamentary conductors in two major features. For in situ conductors, the filaments are discontinuous and have much smaller dimensions. This means that there must be a substantial amount of filament-filament coupling through the Cu and that the Cu-Nb3Sn interface area is comparable to the grain boundary area. The filaments for in situ wire normally have a lacy ribbon shape, 1 grain thick and about 8 to 12 grains wide. This is in contrast to the rather thick (~1 µm) Nb3Sn layers found in bronze process material.
Electromagnetic Properties of Nuclei at High Spins

A photon emitted by an excited state is likely to carry away, at most, 1 or 2ft of angular momentum. Therefore, a profusion of photons is needed to deexcite the rapidly rotating states of nuclei formed by heavy-ion reactions. The study of electromagnetic properties has become the primary source of information on nuclear structure at high spins and, also, at the warm temperatures present in the initial stage of the electromagnetic cascade process. The purpose of this paper is a review of the E1, M1, and E2 properties of such highly excited states, in order to set the stage with theoretical props for the section on this topic in the present volume. This review does not aspire to completeness or a fair distribution of credit for past achievements, but does attempt to highlight the major current research topics in the field. A chart of these topics in the plane of energy versus angular momentum is given in Fig. 1. They involve both the properties of the rotating but “cold” states on or near the yrast line, which can be experimentally resolved as discrete states, and of the increasingly closely spaced levels at higher temperature. The former reveal the response of nuclear structure to rotation, and the latter provide unique insight into the transition of a quantum system from order to chaos.
Shakow, David (1901–81)

David Shakow (1901–81) made significant scientific and professional contributions to the field of clinical psychology. As part of an interdisciplinary team of researchers at Worcester State Hospital and later at the National Institute of Mental Health, Shakow applied experimental methods to the study of the psychological nature of the schizophrenic condition, his work culminating in a cognitive theory of schizophrenia, known as segmental set theory. His work helped to establish new standards for experimental rigor in the field. Shakow also played a critical role in the development of the scientist–practitioner model in clinical psychology. Keywords: Boulder model; scientist-practitioner model; Worcester State Hospital; schizophrenia
Understanding thermal magnetic noise spectra of spin valve heads

In this paper, we present a combined experimental and micromagnetic modeling study to investigate the correlation between mug-noise spectral characteristics and the micromagnetic state of the PM layer at the abutted junction.
Abstract 2927: Rapamycin decreases expression of thymidylate synthase and enhances the response to pemetrexed in preclinical studies and a Phase I/II clinical study of subjects with non-small cell lung cancer

Non-small-cell lung cancer (NSCLC) accounts for 80-85% of lung cancers and almost half of patients with newly diagnosed NSCLC have metastatic disease. Platinum-based chemotherapy regimens given as first-line treatment for advanced NSCLC patients with metastasis are standard but have modest response rates. Pemetrexed is well tolerated and inhibits several folate-dependent enzymes including thymidylate synthase, TS. Increased expression of TS confers resistance to pemetrexed in vitro and is a predictive factor for poor response to pemetrexed. Rapamycin is a mTOR inhibitor and suppresses protein synthesis. Here, we show that rapamycin decreases endogenous expression of TS in NSCLC cells. The combination of rapamycin and pemetrexed synergistically inhibits NSCLC cell proliferation and enhances the inhibition of 4E-binding protein 1 (4E-BP1) activation that is regulated by mTOR. Although pemetrexed as a single agent upregulated expression of TS, pretreatment with rapamycin suppressed pemetrexed-upregulated TS expression. In vivo, the combination of rapamycin and pemetrexed inhibited the growth of NSCLC xenografts, which correlated with decreased mTOR activity and inhibition of pemetrexed-induced upregulated expression of TS. Based on these preclinical data, we have conducted a Phase I/II clinical trial combining rapamycin and pemetrexed in subjects with relapsed NSCLC. This regimen was well tolerated, and resulted in a 22% partial response rate that is above what is expected for response to single agent pemetrexed (9%). In biomarker analyses, pretreatment with rapamycin decreased the expression of TS in peripheral blood mononuclear cells, which correlated with increased progression free survival. Collectively, these studies identify rapamycin and pemetrexed as an effective combination in NSCLC, and suggest that rapamycin enhances the efficacy of pemetrexed by suppressing TS expression. Citation Format: Shigeru Kawabata, Chun-Te Chiang, Regan M. Memmott, Takefumi Komiya, Joell J. Gills, Phillip A. Dennis. Rapamycin decreases expression of thymidylate synthase and enhances the response to pemetrexed in preclinical studies and a Phase I/II clinical study of subjects with non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2927. doi:10.1158/1538-7445.AM2014-2927
Effects of a whey protein product and spray-dried animal plasma on growth performance of weanling pigs.

Five experiments were conducted to evaluate the effects of a high-protein, whey protein product (WPP; 73% CP, 6.8% lysine, 12.8% fat, and 5% lactose) and spray-dried animal plasma (SDAP) on growth performance of weanling pigs. In all experiments, pigs were fed experimental diets from d 0 to 14 after weaning in a pelleted form and then a common diet in meal form for the remainder of the experiment. Dietary treatments were established by substituting WPP or SDAP for dried skim milk (Exp. 1) or soybean meal (Exp. 2, 3, 4, and 5) in the control diet. In Exp. 1, we maintained a constant level of lactose in all diets by adjusting the amount of added crystalline lactose. The amount of lactose in diets used in Exp. 2 through 5 varied slightly by the addition of WPP. In Exp. 1 and 2, 180 weanling pigs (initially 5.8 kg and 19 +/- 1 d of age or 5.5 kg and 17 +/- 1 d of age, respectively) were used. Treatment diets contained SDAP (2.5 and 5%) or WPP (2.7 and 5.4% in Exp.1, and 2.5 or 5.0% in Exp. 2). In Exp. 1, from d 0 to 7 after weaning, ADG and ADFI increased with increasing SDAP (linear, P < .01). No other treatment effects were observed during the d 0 to 14 period. In Exp. 2, from d 0 to 14 after weaning, ADG and G:F increased (linear, P < .04) with increasing SDAP or WWP. In Exp. 3, 305 weanling pigs (initially 4.1 kg and 12 +/- 1 d of age) were used. The control diet contained 2.5% SDAP. The experimental diets were similar to the control diet but contained an additional 2.5 or 5.0% SDAP or 2.5 or 5.0% WPP. From d 0 to 14 after weaning, ADG, ADFI, and G:F increased (quadratic, P < .05) with increasing SDAP up to 5.0%. Increasing WPP increased ADG (quadratic, P < .07) and ADFI (linear, P < .09). In Exp. 4 and 5, 329 and 756 weanling pigs (initially 4.1 kg and 12 +/- 1 d of age and 5.2 kg and 18 +/- 1 d of age, respectively) were fed diets in which WPP was substituted for 0, 25, 50, 75, and 100% (Exp. 4) or 0, 50, and 100% (Exp. 5) of the SDAP in the control diet. In Exp. 4 and 5, from d 0 to 14 after weaning, pigs fed a 1:1 blend of each protein source had better ADG (quadratic, P < .04) than those only fed SDAP. In conclusion, WPP can be used in combination with or as a total replacement for SDAP in diets for weanling pigs without reducing performance.
Cardiovascular interactions between methionine-enkephalin and substance P in the conscious dog.

Abstract Interactions between the undecapeptide Substance P (SP) and the pentapeptide methionine-enkephalin (Met 5 -ENK) have been described in isolated organ systems and in baroreceptor reflex mechanisms. Previous studies in our laboratory have demonstrated that systemically injected Met 5 -ENK simultaneously increases mean systemic arterial pressure (MAP) and heart rate (HR) in the conscious, chronically instrumented dog. We have now evaluated cardiovascular interactions between SP and Met 5 -ENK. In this model, SP injected intravenously produces a rapid and transient decrease in MAP and increase in HR over the dose range from 1.0 to 10.0 ng/kg. SP does not appear to appreciably alter subsequent responses to Met 5 -ENK. At SP doses of 1.0 ng/kg, the peak hemodynamic response to SP and Met 5 -ENK (35 μg/kg) given together appears to represent a simple summation effect of both drugs on HR and MAP. However, at higher SP doses (5.0 ng/kg), the SP response predominates and is little altered by the presence of Met 5 -ENK. Thus, Met 5 -ENK does appear capable of modulating the hemodynamic responses to SP over certain dose ranges.
A fast numerical algorithm for calculating electromagnetic waves in an inhomogeneous slab

Consider a plane monochromatic electromagnetic wave normally incident on an absorbing dielectric slab, bounded by z = 0 and z = L, and whose electrical parameters e, μ and σ are arbitrary functions of z. The media on either side of the slab have constant but generally different electrical properties. This paper describes an efficient numerical algorithm for calculating the electromagnetic field within the slab, as well as its absolute reflection and transmission coefficients. The waveform within the slab is represented by a new complex dependent variable satisfying a modified (complex) Helmholtz equation to be solved subject to mixed inhomogeneous conditions at the boundaries of the slab. If derivatives are replaced by nth-order centred differences, the difference equation set is linear, sparse and efficiently solved by direct recursion. In this paper, complex arithmetic is avoided by replacing the complex Helmholtz equation with two coupled, real, second-order ordinary differential equations. An algorithm of second-order accuracy is developed which leads to a bitridiagonal difference equation set. Calculations are carried out for a variable-property slab problem which can also be solved analytically. Numerical comparisons indicate that the method is accurate and efficient enough that a desk-top computer is a practical computational machine.
RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation: A tail of two kinases

The transition between initiation and productive elongation during RNA Polymerase II (Pol II) transcription is a well-appreciated point of regulation across many eukaryotes. Elongating Pol II is modified by phosphorylation of serine 2 (Ser2) on its carboxy terminal domain (CTD) by two kinases, Bur1/Ctk1 in yeast and Cdk9/Cdk12 in metazoans. Here, we discuss the roles and regulation of these kinases and their relationship to Pol II elongation control, and focus on recent data from work in C. elegans that point out gaps in our current understand of transcription elongation.
Effects of Transactional form on Environmental Linkages and Power-Dependence Relations

The article provides information on a study which investigated network and environmental linkages between manufacturers and dealers. A discussion is presented about the concept of power and depende...
A parametric representation of ellipses and ellipsoids

Abstract The parametric approach to the specification of geometric form is particularly well suited to the needs of structural geologists. This note illustrates its application to ellipses and ellipsoids which may represent stress, strain, or other rank-2 tensor phenomena in rocks. Compared to traditional functional expressions, parametric equations are simpler, faster to compute, and more meaningful in terms of physical parameters.
Density of Charon formed from a disk generated by the impact of partially differentiated bodies

Abstract Formation of Pluto’s moon Charon from an impact-generated circumplanetary disk has been considered unlikely because of its composition. Such a disk is created by the collision of two similarly sized, differentiated impactors; the disk would contain material from the impactors’ outer portions; and that material has been presumed to be pure water ice. Charon has been predicted to have a density ∼ 1000 kg m - 3 if formed from a disk, much lower than its observed density ≈ 1630 kg m - 3 . Here we reconsider the composition of the circumplanetary disk. We draw on previously presented models to calculate the thermal evolution and internal structure of the impactors, each assumed to have radii ≈ 972 km and mean densities ≈ 2000 kg m - 3 . We show such bodies retain crusts of rock and ice on their surfaces about 46 km thick, comprising about 13% of the impactors’ mass; the outer layers are not pure ice. Provided ≈ 6 % of the total mass of the impactors escapes the system, an escape fraction supported by numerical simulations, the observed densities of Pluto and Charon are reproduced in a scenario involving a circumplanetary disk. Charon’s density does not rule out an origin from an impact-generated disk. We calculate the thermal evolution of Charon if it formed late from an impact-generated disk. While Charon is less heated by radioactive decay than if it formed earlier, the heat of its accretion causes its complete differentiation. Subsurface liquid and cryovolcanism may have existed on Charon, but only until 1.5 Gyr ago. These predictions may be tested by data returned by the New Horizons mission.
Behavioural variants of rat neuroblastoma cells.

Study of the biological function of the cells of the nervous system has benefited from the isolation of cloned glial or neuronal tumour cell lines that can he induced to differentiate in culture1–3. Many of their differentiated properties reflect specific biochemical changes at the cell surface, and we have observed changes in cytoskeletal organization and glycosaminoglycan-containing proteoglycan content in the tissue culture substratum adhesion sites of neuroblastoma cells during neurite extension4. To assist in defining structure function relationships of cell surface components of rodent neuroblastoma cells, I have used two cell-surface-active agents to select for phenotypically-stable variants of these cells which display some unique properties and which will be useful for further biochemical and physiological analyses.
CONSTELLATIONS OF RELIGIOUS ATTITUDES OF PARANOID SCHIZOPHRENICS

Some years ago Chaplain Boisen ( 1 ) wrote, "The conclusion follows that certain types of mental disorder and certain types of religious experience are alike attempts at reorganization." He has devoted his life to this thesis and has profoundly influenced today's psychiatric thinking in this area. Boisen proposes the classification of symptoms into religious, mystic or world-reconstruction ideas as opposed to the hostile reaction to supposed external threat and persecution. The former represents an internalization and incorporation as opposed to the latter, which involves external projection and rejection. Boisen has devoted his attention to the religious symptoms. His thinking about the type of person showing such symptoms is interesting and convincing, but what are the typological findings stemming from factor analytic views of psychotic reactions? Factor analyses of paranoid schizophrenics invariably reveal, among others, his two clear-cut types (4, 5 ) . Just recently Boisen, Jenkins, and Lorr ( 2 ) presented a factor analysis of delusional thinking. Again, these two factors emerged, but this time, without any others. This study is directed at determining the empirical constellations of religious attitudes that might exist among paranoid schizophrenics. It is hoped that research in the area of religious attitudes may be stimulated. PROCEDURE The 25 Ss in this study were drawn from a total of 51 recently diagnosed hospitalized schizophrenics. All Ss were listed in the records as Protestant. Seven patients were excluded because they were hostile and uncooperative, nine because they were querulous and perplexed, three because they were suspicious, three because they had an attention defect, and four because they showed much internal test inconsistency. The test items were developed by the authors and drew heavily upon a book by Chave ( 3 ) . Within this book there are quite a few semiformal tests of religious attitude developed by Chave and L. L. Thurstone. The original 128 items2 included seven duplications. These seven duplications made it pos-
Bladder dysfunction with herpes zoster

Abstract Herpes zoster with bladder involvement.is rare. Forty-eight cases including one of our own are reviewed. Bladder symptoms appear when sacral nerve roots are involved. Patients generally have either urinary retention or irritative symptoms. Since pain followed by skin rash usually precedes the development of bladder symptoms, there usually is no diagnostic dilemma. Patients with paralytic symptoms tend to have negative cystoscopic findings, while those with irritative symptoms tend to have mucosal lesions compatible with herpes zoster lesions. The disease is self-limited, and symptomatic management is adequate.
Act and Principle Contractualism

Unrejectability is the property shared by things no one could reasonably reject. Following the lead of T. M. Scanlon, modern contractualists hold Principle Contractualism : An act is obligatory when conformity to unrejectable principles requires its performance. This article entertains Act Contractualism : An act is obligatory when its performance is unrejectable. The article hypothesizes that Principle Contractualism owes its initial plausibility to the assumption that following it somehow realizes unrejectability, if only indirectly. The article then argues that, whereas following Act Contractualism realizes unrejectability, following Principle Contractualism realizes a convoluted, principle-mediated, non-causal conformity relation between acts and unrejectability. But then the notion that this relation is what matters ultimately in action does not seem to enjoy independent plausibility. After interrogating Scanlon's objection that the challenge to the principle-based nature of contractualism is ‘misconceived’, I conclude that Act Contractualism is the more fitting contractualist theory of obligation.
Shear correction factors and an energy-consistent beam theory

Abstract Presented here is a new derivation of shear correction factors for isotropic beams by matching the exact shear stress resultants and shear strain energy with those of the equivalent first-order shear deformation theory. Moreover, a new method of deriving in-plane and shear warping functions from available elasticity solutions is shown. The derived exact warping functions can be used to check the accuracy of a two-dimensional sectional finite-element analysis of central solutions. The physical meaning of a shear correction factor is shown to be the ratio of the geometric average to the energy average of the transverse shear strain on a cross section. Examples are shown for circular and rectangular cross sections, and the obtained shear correction factors are compared with those of Cowper (1966) . The energy-averaged shear representative is also used to derive Timoshenkos beam theory.
Moments of products of automorphic L-functions

Abstract Assuming the generalized Riemann hypothesis, we prove upper bounds for moments of arbitrary products of automorphic L-functions and for Dedekind zeta-functions of Galois number fields on the critical line. As an application, we use these bounds to estimate the variance of the coefficients of these zeta- and L-functions in short intervals. We also prove upper bounds for moments of products of central values of automorphic L-functions twisted by quadratic Dirichlet characters and averaged over fundamental discriminants.
Micro-opto-electro-mechanical system (MOEMS) for microstructure manipulation and optical characterization

Microstructure manipulation is a fundamental process to further the study of biology and medicine, as well as to advance micro- and nano-system applications. The manipulation of micro and nanostructures has been achieved through various microgripper devices developed recently, which lead to advances in single cell manipulation and micromachine assembly. However, the physical, mechanical, optical and chemical information about the microstructure under study is usually extracted from macroscopic instrumentation, such as confocal microscopy and Raman spectroscopy. In this paper we describe the design, simulation, fabrication and characterization (mechanical and optical) of a novel Micro-Opto-Electro-Mechanical-System (MOEMS) optical microgripper. This is the first device of this kind, which enables the direct manipulation, mechanical characterization, and simultaneous optical characterization of microstructures. Optical fluorescence measurements or identification, as well as absorption spectroscopy are possible with this new device. The device is implemented in SU-8 due to its suitable optical and mechanical properties. The current generation of the device was designed to manipulate structures with dimensions lower than ~5 μm.
Membrane Proteins Involved in Phagocyte Adherence to Endothelium

Article synthese sur les proteines de surface cellulaire impliquees dans l'adherence des phagocytes au niveau de l'endothelium de la veine ombilicale dans les mecanismes inflammatoires. Le role d'antigenes tels que l'antigene cD18 dans l'emigration in vivo des phagocytes est etudie
The organization of macronuclear rDNA molecules of four hypotrichous ciliated protozoans.

We have compared the structure of macronuclear DNA molecules that contain rRNA genes of four hypotricous ciliates, Stylonychia pustulata, Euplotes aediculatus, Oxytricha fallax and Oxytricha nova. The macronuclear rDNA, like all macronuclear DNA in hypotrichs, exists as achromosomal molecules of approximately single-gene size. The rDNA molecules have been cloned intact as recombinant plasmids and analyzed by restriction mapping and Southern hybridization. The sites of restriction enzymes BamHI, EcoRI, HindIII, PstI, PsuII and XhoI have similar but not identical patterns in Stylonychia and the two Oxytricha rDNAs. The restriction pattern of Euplotes rDNA is unlike those of the other three, with only one site of seventeen in the same position. Despite this divergence in nucleotide sequence, the overall structure of the rDNA molecules in the four hypotrichs is constant. The size of all the rDNA molecules is the same, 7.49 kb. Also, the positions of the regions coding for 19S and 25S rRNA are alike. The 25S coding region is at the 5′ end of the DNA template strand (3′ end of the RNA transcript), within 500 base pairs of the terminus of the DNA molecule. The 19S coding region is adjacent to the 25S region with less than 500 base pairs of spacer lying between the two genes. The largest non-coding sequence is at the 3′ end of the DNA molecule adjoining the 19S RNA gene. The 3′ non-coding regions show greater sequence divergence among the different rDNAs than do the coding regions. The similarity in size and organization of these molecules and the variability in the restriction patterns suggest that the gene structure is under tighter evolutionary constraint than is the primary nucleotide sequence.
Bayesian Analysis of Hierarchical Pattern-Mixture Models for Clinical Trials Data with Attrition and Comparisons to Commonly Used Ad-Hoc and Model-Based Approaches

This article addresses the problem of making scientifically sound inferences from clinical trials data with attrition, when reasons of attrition seem related to the outcomes of interest. The problem is particularly difficult when the effect of a covariate is to be estimated and if the dropout mechanism appears to operate differently at different levels of the covariate. In this context, multiple imputation under a multilevel pattern-mixture model that allows random variation across dropout groups is presented. Using simulated data generated around an alcoholic hepatitis trial, we compare the performance of this model and commonly used ad-hoc and model-based approaches.
Self-Blame and Self-Destruction in Women Sexually Abused as Children.

ABSTRACT Women who have been sexually abused as children often experience self-blame and self-destructive behavior as adults, and stigmatization resulting from self-blame has been suggested as a mediating factor. Two studies were conducted to assess the relationship between self-blame and self-destructive behavior in women sexually abused as children: (1) In a clinical sample of women sexually abused as children, high self-blamers were compared with low self-blamers on depression, self-destructive behavior, and reasons for living. Women who had high self-blame were more depressed and suicidal, were more likely to have self-mutilated, and had weaker survival and coping beliefs than low self-blamers; (2) In a college sample, women who had high self-blame were more depressed and suicidal, had weaker survival and coping beliefs, and had more fear of suicide and fear of social disapproval than low self-blamers. Depression, self-blame, and reasons for living predicted a significant amount of the variance in sui...
Stability, normalization and accuracy of MODIS-derived estimates of live fuel moisture for southern California chaparral

Time series of spectral vegetation indices (SVIs) derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and live fuel moisture (LFM) data for chaparral vegetation of southern California were extended to include one of the driest (2004) and one of the wettest (2005) years on record. Independent, spatially varying field-based estimates of LFM enabled accuracy of MODIS-derived estimates to be quantified. Pixel-based scaling of SVI values based on maximum and minimum values of the time series reduced effects of varying vegetation cover and substantially reduced root mean square errors for two of the three SVIs tested.
Hard coatings with high temperature adaptive lubrication and contact thermal management: review

Abstract Progress in the design and exploration of hard coatings with high temperature adaptive behavior in tribological contacts is reviewed. When coupled with most recent surface engineering strategies for high temperature contact thermal management, this progress opens a huge opportunity for adaptive coating applications on machine parts, where oils and coolants are commonly used. The adaptive mechanisms discussed here include metal diffusion and formation of lubricant phases at worn surfaces, thermally- and mechanically-induced phase transitions in hexagonal solids, contact surface tribo-chemical evolutions to form phases with low melting point, formation of easy to shear solid oxides, and others. All of these adaptive mechanisms are combined in nanocomposite coatings with synergistic self-adaptation of surface structure and chemistry to lubricate from ambient temperatures to 1000 °C and provide surface chemical and structural reversibility during temperature cycling to maintain low friction coefficients. The review also highlights emerging surface adaptive concepts, where advances with ab initio modeling of intrinsically layered solids point to new compositions for thermally stable, easy to shear ceramic coatings, load- and temperature-adaptive surfaces with arrays of compliant carbon and boron nitride nanotubes as well as low friction two-dimensional structures. Approaches for self-regulation of coating thermal conductivity, heat flow, and thermal spike mitigations are discussed in the context of surface structure evolution and phase transitions. Future progress is linked to the development of in situ exploration techniques, capable of identifying adaptive surface chemistry and structural evolutions in broad temperature regimes. When combined with predictive modeling, such approaches drastically accelerate adaptive coating developments. The review identifies opportunities, strategies, and challenges for designs and applications of hard coatings with high temperature adaptive lubrication and contact thermal management.
Social structure and the effects of conformity

Conformity is an often criticized feature of human belief formation. Although generally regarded as a negative influence on reliability, it has not been widely studied. This paper attempts to determine the epistemic effects of conformity by analyzing a mathematical model of this behavior. In addition to investigating the effect of conformity on the reliability of individuals and groups, this paper attempts to determine the optimal structure for conformity. That is, supposing that conformity is inevitable, what is the best way for conformity effects to occur? The paper finds that in some contexts conformity effects are reliability inducing and, more surprisingly even when it is counterproductive, not all methods for reducing its effect are helpful. These conclusions contribute to a larger discussion in social epistemology regarding the effect of social behavior on individual reliability.
Abstract C146: LNA (locked nucleic acid) oligonucleotide based GLI2 RNA antagonist EZN‐4482 effectively inhibited tumor growth and increased survival of animals with liver metastasis

Background: The Hedgehog (Hh) pathway has been implicated in the growth of a number of human malignancies and cancer stem cells. In the presence of Hh ligands, PTCH1 inhibition of a membrane protein, Smoothened (SMO), is relieved. SMO activation triggers a cascade of downstream events that ultimately activate the zinc finger transcription factors GLI2 and GLI3 and induce transcription of their target genes such as GLI1, PTCH1, Cyclin D, and BCL2. Emerging evidence suggests that GLI1 and GLI2 represent the main activators of Hh pathway due to amplification, overexpression of Hh ligand, and mutations of components along the Hh pathway. Therefore, specific down regulation of GLIs with RNA antagonists such as siRNA and antisense molecules may offer an effective therapeutic approach for cancer treatment. We reveal here the biological activities of LNA‐based GLI2 mRNA antagonist, EZN‐4482 and 4496. Material and Methods:In vitro, the ability of the antagonists to down modulate mRNA and cell growth was evaluated by qRT‐PCR and MTS respectively. In vivo, GLI2 mRNA down‐modulation in tumors, which were grown on the flank of nude mice, was evaluated after intravenous administration of the antagonists. The effect of antagonists on tumor growth and survival of mice were evaluated in PC3 prostate tumor grown on the flank and in A549 lung carcinoma cells that had metastasized to the liver respectively. Results: Both antagonists, when transfected into tumor cells, were potent down‐modulators of GLI2 mRNA (IC50 ≤ 2 nM), resulting caspase ativation and growth inhibition. Interestingly, we found that without any transfection reagent, 1–10 micromolar concentrations of these antagonists were able to down modulate GLI2 mRNA and inhibit the growth of multiple cell lines while their scrambled control oligonucleotides showed no effect, suggesting that the effect was specific. In mice, EZN‐4482 (3 mg/kg given q3d x4) down modulated GLI2 mRNA in PC3 prostate tumors. Moreover, using murine specific probes, we found EZN‐4482 also inhibited GLI1/2 and PTCH1 in the same tumors. Moderate tumor growth inhibition was found with EZN‐4482 in the PC3 xenograft model. Additionally, we show that EZN‐4482 prolonged the survival of animals with liver metastasis derived from A549 cells. Conclusions: GLI2 antagonists potently and specifically inhibited GLI2 mRNA expression and tumor growth in two tumor models. The possible mechanisms of efficacy include inhibition of mRNA levels of GLI1/2 and PTCH1 in mouse stromal cells. While small molecule inhibitors of SMO are being evaluated clinically, this approach is limited to tumors where pathway activation is upstream of GLIs or tumors that are resistant to such inhibitors. Therefore, a GLI2 RNA antagonist may be an effective therapy to treat a broad spectrum of cancers including ones that fail treatment with SMO inhibitor therapy. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C146.
DOMAIN STRUCTURE OF THE STAPHYLOCOCCUS AUREUS COLLAGEN ADHESIN

Sequence analysis of surface proteins from Gram-positive bacteria indicates a composite organization consisting of unique and repeated segments. Thus, these proteins may contain discrete domains that could fold independently. In this paper, we have used a panel of biophysical methods, including gel permeation chromatography, analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy, to analyze the structural organization of the Staphylococcus aureus collagen adhesin, CNA. Our results indicate that the structure, function, and folding of the ligand-binding domain (A) are not affected by the presence or absence of the other major domain (B). In addition, little or no interaction is observed between the nearly identical repeat units within the B domain. We propose that CNA is indeed a mosaic protein in which the different domains previously indicated by sequence analysis operate independently.
Er2O3 for high-gain waveguide amplifiers

Following the demonstration of room-temperature luminescence, Er2O3 has been explored as a high-gain medium for ultra-compact waveguide amplifiers. With sputtered and annealed films, we measure three radiative lifetimes (7 ms, 0.8 ms, and 0.5 ms) and upconversion coefficients at 4.2 K. We have correlated these measurements with three crystalline phases: the thermodynamically stable bcc phase and the metastable fcc and hcp phases. The 7-ms lifetime is correlated with the fcc phase, implying the metastable crystal state has a profound influence on inhibiting upconversion interaction between neighbor Er atoms. Measurements indicate optical gain >3 dB/cm is possible.
Computations of Unsteady Cavitation With a Pressure-Based Method

A computational approach based on the conservative form of the Favre-averaged Navier-Stokes equations, transport equation-based turbulent cavitation models and a pressure-based operator-splitting algorithm is applied to study turbulent cavitating flows through convergent-divergent nozzles. The implications of the compressibility effect, reflected via the speed of sound definition in the two-phase mixture, are assessed with two modeling approaches. Depending on the geometric confinement of the nozzle, compressibility model, and cavitation numbers, auto-oscillations and quasi-steady behaviors are observed. Detailed flow structures and cavitation dynamics are highlighted, and implications of the cavitation model discussed.Copyright © 2003 by ASME
Epidemiology and potential methods for prevention of neonatal intestinal viral infections.

Viral infections of the gastrointestinal tract remain a major problem during the neonatal period. In addition to causing acute diarrhea, rotaviruses and other enteric viruses may be involved in the pathogenesis of necrotizing enterocolitis and other neonatal enteric diseases. There are several potential methods for the prevention and treatment of gastrointestinal viral infections. Antiviral immunoglobulins might be used to inhibit intestinal viral replication. Since only small concentrations of serum immunoglobulins are present at mucosal surfaces, oral administration of immunoglobulins might be utilized to maximize antiviral efficacy. Alternatively, inhibitors of specific glycoproteins of virus-cell binding might be used to prevent the productive infection of intestinal epithelial cells. In addition, since many enteric viruses require proteolytic enzymes for protein cleavage, protease inhibitors may prove effective for inhibition of intestinal viral replication. At this time, these methods have proven useful for the inhibition of rotavirus infection in experimental animals. The successful application of these and other methods for the prevention of enteric infections in humans might substantially reduce the morbidity and mortality associated with enteric diseases in high-risk neonates. Viral infections remain important causes of morbidity and mortality in low-birth-weight infants. While a number of organ systems can be infected by virus during the newborn period, the neonatal gastrointestinal tract is an important target organ for these pathogenic agents. Epidemiologic studies have demonstrated that the replication of viruses within the neonatal intestinal tract can lead to a number of clinical consequences, ranging in severity from self-limited watery diarrhea to more prolonged di
Magnitude of the placebo effect in randomized trials of antiepileptic agents.

Abstract Placebo-controlled randomized trials ideally produce unbiased estimates of the treatment effect after accounting for nonpharmacological effects (regression to the mean, Hawthorne, and placebo effects). Recognizing that the magnitude of these effects may help understand why investigators need to control for them, we sought to measure this magnitude. We reviewed published meta-analyses of randomized, placebo-controlled add-on trials of antiepileptic medications versus placebo, included in the Cochrane Library. In randomized trials of antiepileptic agents for epilepsy, 9.3–16.6% of patients in the placebo arm had a >50% reduction in seizure frequency. This effect represents 20–50% of the effect observed with active agents. Because patients with epilepsy in the placebo arm of randomized trials experience a large clinical benefit due to nonpharmacological effects, randomized controlled trials are necessary to gauge the true magnitude of the treatment effect of new antiepileptic agents.
GENETIC VARIATION IN ALETES ACAULIS AND ITS RELATIVE, THE NARROW ENDEMIC A. HUMILIS (APIACEAE).

We compared the organization of genetic variability in Aletes humilis, a species restricted to seven populations in north-central Colorado, with A. acaulis, a closely related widespread species. Genetic variability was scored at 11 electrophoretically detectable protein loci. Nine of these loci were polymorphic (i.e., P > 0.95) in both taxa, and were used for interpopulation and interspecific comparisons. Levels of genetic variability and patterns of organization of this variability are very comparable in both species. In contrast to many other narrow endemics, A. humilis is not genetically depauperate when compared to its presumed progenitor. Both biochemical and morphological evidence suggest that A. humilis is derived from A. acaulis; the comparable levels of variability in the two species suggest that A. humilis was derived from a source containing a substantial portion of the original A. acaulis genome, because there is no evidence of a genetic bottleneck or appreciable loss of allelic variability.
Early dysregulation of the memory CD8+ T cell repertoire leads to compromised immune responses to secondary viral infection in the aged.

Background Virus-specific memory CD8+ T cells persist long after infection is resolved and are important for mediating recall responses to secondary infection. Although the number of memory T cells remains relatively constant over time, little is known about the overall stability of the memory T cell pool, particularly with respect to T cell clonal diversity. In this study we developed a novel assay to measure the composition of the memory T cell pool in large cohorts of mice over time following respiratory virus infection.
Real-time in-situ determination of free Cu(II) at picomolar levels in sea water using a fluorescence lifetime-based fiber optic biosensor

A continuing issue in chemical oceanography and environmental monitoring is the need for frequent and continuous monitoring of analytes in complex matrices such as sea water and ground waters. Particularly for analytes at trace levels such as Cu(II) in sea water, sampling and analysis of discrete specimens is costly, slow, labor intensive, employs ship time inefficiently, and risks error by contamination. We have developed a fluorescence lifetime- based fiber optic biosensor which demonstrates real time determination of free Cu(II) in coastal waters, in situ, with a subpicomolar detection limit.
A new way to look at fat.

Stimulated Raman scattering (SRS) microscopy is used to directly visualize lipids in cells and model organisms, and facilitates screening for genes involved in fat storage.
Visualizing genetic influences on human brain functions.

Abstract Egan and colleagues (2003), in this issue of Cell , integrate genetics and functional brain imaging by showing that variation in the human brain-derived neurotrophic factor (BDNF) gene is associated with variation in episodic memory ability and in hippocampal neurochemistry and function.
Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients

Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG.
Factors that control Jc in high Tc superconductors

Abstract A study of critical currents, flux creep and vortex line energy was undertaken for a variety of materials to determine some of the factors that control the intragranular critical current. Creep measurements for Nd 1.85 Ce 0.15 CuO 4 and TI 2 Ba 2 Ca 2 Cu 3 O 10 , plotted as a function of reduced temperature, t = T / T c , show essentially the same behaviour. This implies that the Nd compound, which has a much longer coherence distance and may have many electron carriers, has the same effective pinning potential to kT ratio at the same reduced temperature. Hence these two factors do not seem to be dominant in controlling J c . A change in the vortex line energy, however, seems to be very important. With the addition of small amounts of Fe, the line energy and J c both fall exponentially with Fe content in Y 1 Ba 2 (Cu 1− x , Fe x ) 3 O 7−σ . Hence the free energy per unit length of vortex is a very important factor controlling the intragranular critical currents.
Comparisons of HELIOS, ORIGEN2, and monteburns calculated 241Am and 243Am concentrations to measured values for PWR, BWR, and VVER spent fuel

A study was performed at Los Alamos National Laboratory to explore the accuracy of several reactor analysis codes in calculating 241 Am and 243Am concentrations in light water reactor spent fuel. Calculated higher-actinide concentrations were compared to measured values from the literature for three reactor fuels. The fuel samples were taken from the Mihama Unit 3 pressurized water reactor, the Garigliano boiling water reactor, and a VVER-440. The 241Am and 243Am concentrations were calculated using the HELIOS-1.4 lattice-physics code, the ORIGEN2 burnup code, and a linked MCNP/ORIGEN2 code named Monteburns 3.01. Comparisons were made between the calculated and measured values. It was determined that all codes performed consistently well for the Mihama Unit 3 measurements (within ±5% for 241Am and ±20% for 243Am) and the Garigliano measurements (within ±12% for 241 Am and ±20% for 243Am). It was determined that the ORIGEN2 pressurized water reactor libraries are insufficient for the VVER-440 measurements....