cssi/SciSciGPT-SciSciNet huggingface dataset:
Preparation and Dielectric Measurements of the Rare Earth Green Phases R2BaCuO(5-x) (R = Y, Sm, Gd, Dy, Ho, Er, Yb)

It has been demonstrated that R2BaCuO(5-x) (R = Y, Sm, Gd, Dy, Ho, Er, Yb) does not undergo significant densification unless the sintering temperatures are near the incongruent melting point or the sintering times are long. Good quality powders of Y2BaCuO(5-x) have been synthesized by using oxide raw materials or precursors such as acetates and nitrates. The acetates- and the nitrates-derived yttrium green phase resulted in finer particle sizes, acceptable dielectric properties and lower melting temperatures than those processed via oxide raw materials. The hot pressing technique has been employed to produce a dense R2BaCuO(5-x) (R=Y,Gd) substrate with satisfactory dielectric properties. Reactivity to reducing conditions, i.e. graphite die, limited the optimization of the properties. A high sensitivity to the annealing atmosphere has been demonstrated in Y2BaCuO,.,,. Oxygen treatment at 950 OC has been shown to improve the dielectric properties while treatment in nitrogen, at the same temperature, degraded desirable properties. A high sensitivity to the annealing atmosphere has been demonstrated in Y2BaCuO(5-x). Oxygen treatment at 950 C has been shown to improve the dielectric properties while treatment in nitrogen, at the same temperature, degraded desirable properties. The dielectric constants of the rare earth green phases R2BaCuO(5-x) were found to be low. Relaxation peaks were detected at low temperatures (T less than 150 K) and at high temperatures (150 less than T greater than 420 K). The dielectric losses and conductivities at 77 K were measured to be in the range of 10(exp -4) and 10(exp -12) (Omega-cm)(exp -1), respectively. Many parameters were found to exhibit dependencies on the rare earth cation sizes.
Studies on fraction-I protein: I. Effect of crystallization of fraction-I protein from tobacco leaves on ribulose diphosphate carboxylase activity

Abstract Conditions of pH and NaCl concentration were established whereby highly purified Fraction-I protein was crystallized. Identity of the crystalline material with Fraction-I protein was shown by ultraviolet absorption, analytical centrifugation, immunological properties, and Sephadex chromatography. The specific ribulose diphosphate carboxylase 6 (3-phospho- d -glycerate carboxy-lyase (EC 4.1.1.39)) activity of crystallized Fraction-I protein was higher than either the purified Fraction-I protein used for crystallization or the protein which remained dissolved in the mother liquor. The crystals are composed of 12 faces, each being parallelograms, united to form 6 apices where 3 faces are joined and 8 apices where 4 faces are joined. The crystals show little birefringence. A model corresponding to the appearance of the crystals was constructed by combining an octahedron with a cube where 2/√2 was the ratio of the longer to shorter diameter, the angles between faces were 60°, and the acute angle of a face was 70.32° compared to the obtuse angle of 109.68°.
Articular Synovial Chondromatosis

Synovial chondromatosis is a rare disease in which multiple, metaplastic, cartilaginous masses form in the synovial membrane. These may calcify or ossify. The affection is monarticular and most commonly involves the knee. Although the clinical features are usually completely non-specific, the roentgenogram often provides important diagnostic information. Other entities that produce intraarticular and intrasynovial osteocartilaginous masses should not be included with synovial chondromatosis. In the present series of thirty-two cases, synovectomy proved to be a good form of treatment. Although cellular activity within foci in twenty-three of these thirty-two cases suggested the possibility of chondrosarcoma, the course was not clinically malignant in any of the cases.
Betting Against Efficiency: Behavioral Finance in an Nfl Gambling Exchange

Although it may be a stretch to claim that the efficient markets hypothesis of Eugene Fama (1970) has been toppled, recent work has uncovered both empirical and theoretical opposition to Fama's pillar of financial theory. Much of this substantial body of research has focused on the world's financial markets. The explosion of internet-based betting exchanges and information markets, however, provides a rich and simple dataset with which to examine market behavior. These markets provide an especially interesting environment under which to study pricing behavior because the fundamental value is always revealed at the close of each contract, unlike stock prices that merely provide repeated estimations of fundamental value. Concentrating on trading in contracts with the outcomes of National Football League (NFL) games as the underlying event, this paper first revisits two of behavioral finance's major theories: overreaction and underreaction. These behavioral theories make somewhat conflicting predictions about investor activities, and I determine what evidence of each theory exists in NFL gambling markets. The paper then focuses on two hypothesized anomalies that are more specific to NFL wagering. These contradictions to the weak and semi-strong form of the efficient markets hypothesis in the NFL market I label "implication ignorance" and "improper normal curve pricing." Implication ignorance involves the mispricing of contracts that depend on multiple distinct events. This analysis examines the prices of parlay contracts with an eye toward the behavioral work of Tversky and Kahneman (1974). Improper normal curve pricing investigates the prices of different point spread contracts in the context of Stern's (1991) normal curve approximation of the margin of victory distribution. Though no evidence of overreaction or underreaction in NFL trading is found, there is strong evidence of implication ignorance and marginal evidence of improper normal curve pricing.
Nonparametric M-regression with free knot splines

Many problems of practical interest can be formulated as the nonparametric estimation of a certain function such as a regression function, logistic or other generalized regression function, density function, conditional density function, hazard function, or conditional hazard function. Extended linear modeling provides a convenient theoretical framework for using polynomial splines and their selected tensor products in such function estimation problems and especially for obtaining rates of convergence of the resulting estimates in a unified manner. For a long time the theoretical results were restricted to fixed knot splines and to log-likelihood functions that were twice continuously differentiable. Recently, Stone and Huang extended the theory to handle free knot splines. In the present paper, the theory is further extended to handle contexts in which the log-likelihood function may not be differentiable. Specifically, we establish rates of convergence for estimation based on free knot splines in the context of nonparametric regression corresponding to M-estimates, which includes least absolute deviations (LAD) regression, quantile regression, and robust regression as special cases.
The changing face of HIV vaccine research

While there has been remarkable progress in understanding the biology of HIV-1 and its recognition by the human immune system, we have not yet developed an efficacious HIV-1 vaccine. Vaccine challenges include the genetic diversity and mutability of HIV-1 which create a plethora of constantly changing antigens, the structural features of the viral envelope glycoprotein that disguise conserved receptor-binding sites from the immune system, and the presence of carbohydrate moieties that shield potential epitopes from antibodies. Despite these challenges, there has been significant scientific progress in recent years. In 2009, a large-scale clinical trial known as RV144 demonstrated that a HIV-1 vaccine could modestly reduce the incidence of HIV-1 infection. Further, the identification of broadly neutralizing monoclonal antibodies (such as VRC01, a human monoclonal antibody capable of neutralizing over 90% of natural HIV-1 isolates, as well as PG and PGT antibodies that recognize conserved glycopeptide epitopes) has revealed new opportunities for vaccine design. Our ability to understand HIV-1 structure and antibody epitopes at the atomic level, the rapid advance of computational and bioinformatics approaches to immunogen design, and our newly acquired knowledge that it is possible for a vaccine to reduce the risk of HIV-1 infection, have all opened up new and promising pathways towards the development of an urgently needed effective HIV-1 vaccine. This article summarizes challenges to the development of an HIV-1 vaccine, lessons learned from scientific investigation and completed vaccine trials, and promising developments in HIV-1 vaccine design.
Thermoelastic damping in the contour-mode vibrations of micro- and nano-electromechanical circular thin-plate resonators

Abstract This paper presents an analytical study on thermoelastic damping (TED) in the contour-mode vibrations of micro- and nano-electromechanical circular thin-plate resonators. Instead of expressing TED in terms of a commonly used complex frequency value, this work calculates TED by using a thermal-energy approach in which the generation of thermal energy per cycle of vibration is considered. To demonstrate its validity, this thermal-energy approach is first utilized to tackle the well-known TED in a flexural-mode beam resonator. Then, it is extended to analyzing TED in the contour-mode vibrations of a circular thin-plate micro-/nano-resonator. Consequently, the behavior of TED versus the key design parameters, namely thin-plate radius and resonant frequency, is predicted, and the attainable quality factors of such type of resonators are defined. From this work, it is found that the QTED of the contour-mode vibrations of a circular thin-plate resonator is well above 1×106 when its resonant frequency is below 1 GHz and TED becomes a significant source of dissipation for circular thin-plate resonators at the nanometer scale.
EIT Reconstruction of Static Images by a Genetic Algorithm Approach

: A genetic algorithm (GA) approach is proposed for the reconstruction of static images in electrical impedance tomography (EIT). Genetic algorithms can be demonstrated to possess several advantages over more conventional “gradient-based” techniques. In particular, they are implicitly parallel and realize a good compromise between “exploration” and “exploitation”, thus being more robust against the problem of false minima. The results of GA-EIT in numerical experiments are presented, compared to those obtained by other, more established inversion methods, such as the modified Newton-Raphson method and the double-constraint method. The GA approach is relatively expensive in terms of computation time and resources, requiring (for example) from several minutes to tens of minutes on a Pentium Pro 200-based machine for normal-size EIT problems. This currently limits the applicability of GA-EIT to the field of static imaging. However, in light of the development trend in the field of computing, an extension to real-time dynamic imaging applications is not inconceivable in the near future.
Effects of environmental enrichment on nicotine-induced sensitization and cross-sensitization to d-amphetamine in rats

Abstract Introduction Research indicates that adolescent nicotine exposure may predispose individuals to use other psychostimulants later in adulthood, offering support for the incentive-sensitization theory of addiction. Preclinical studies testing the incentive-sensitization theory show that repeated nicotine exposure in adolescent rats can lead to an increased sensitivity to the motor stimulant effects of nicotine and other psychostimulants in adulthood. Although previous nicotine exposure can increase sensitivity to stimulant drugs, rats raised in enriched conditions (EC) show, decreased sensitivity to psychostimulant drugs compared to rats raised in isolation conditions (IC). Methods We examined whether nicotine sensitization or cross-sensitization to d -amphetamine induced by adolescent nicotine exposure is altered by exposure to environmental enrichment. Adolescent EC and IC male rats received subcutaneous (s.c.) injections of saline or 0.4 mg/kg of nicotine once daily for seven days. Thirty-five days following the last nicotine injection EC and IC animals were challenged with saline, nicotine (0.2 or 0.4 mg/kg) or d -amphetamine (0.5 or 1.0 mg/kg). Results EC rats failed to show nicotine sensitization at either nicotine dose tested while IC rats showed nicotine sensitization following the 0.4 mg/kg nicotine dose. EC rats also failed to show nicotine-induced cross-sensitization to the 0.5 mg/kg dose of d -amphetamine while IC rats displayed cross-sensitization. However, EC rats did exhibit nicotine-induced cross-sensitization to the 1.0 mg/kg dose of d -amphetamine. Conclusion These findings indicate that environmental enrichment can alter the ability of adolescent nicotine exposure to induce sensitization and cross-sensitization in adulthood and may be used as a protectant factor against adolescent nicotine exposure.
Isaiah and Statesmanship

Th e practical difficulty of Plato's Republic, one may suggest, is its disregard of statesmanship, at the same time as it reiterates some of its finest principles. The ideal state is a virtuous mon archy ruled by the philosopher-king, with justice defined as a perfect match of talent and position. It is distinguished from actual states in that knowledge as wisdom rules so perfectly and so divinely that law is unnecessary.1 It is much like a heavenly city—at least like a most enlightened despotism. In the Statesman, Plato admitted the necessity of revision. He revealed that the available stock of human intelligence on earth is insufficient for so divine a prospect and that the humanly best solution must be a government of laws that involves human beings in both their formulation and compliance. Studying the Statesman and the later Laws of Plato, one encounters a book of statecraft in which factors of popular assent and participation cannot be overlooked. At the same time, as Aristotle so aptly reiterated, the virtue of knowledge as wisdom possessed by the ideal monarch is not to be discarded but is to be cultivated by the magistrates and all persons in authority who would perform their roles well.2 Statesmanship requires a knowledge both of the true ends of political society and the means by which they may be attained.
The Inter-Atlantic Paradigm: The Failure of Spanish Medieval Colonization of the Canary and Caribbean Islands

L'A. etudie le paradigme inter-atlantique (contexte comparatif d'analyse) afin d'etudier, d'une part, la transition entre l'histoire medievale espagnole et la construction de l'empire espagnol et, d'autre part, l'echec de la colonisation des Caraibes et des Canaries. Repopulation, confrontation, interdependance economique et symbiose culturelle, n'ont pas fonctionne dans la conquete des Canaries et des Caraibes alors qu'elles reussirent dans la lutte contre les Maures. Les Guanches des Canaries et les Tainos des Caraibes presentaient des traits qui expliquent l'echec de cette colonisation (economies ne correspondant pas aux besoins espagnols, illettrisme et absence de la notion de revelation, etc.).
Electrochemical Growth of Ag2S on Ag(111) Electrodes. Coulometric and X-ray Photoelectron Spectroscopic Analysis of the Stepwise Formation of the First and Second Monolayers of Ag2S

Stepwise electrochemical growth of the first and second monolayers of Ag2S at a Ag(111) electrode in aqueous hydrosulfide (HS-) solutions is reported. The deposition of the first and second monolayers occurs at different electrode potentials and can be resolved in voltammetric experiments prior to the formation of a bulk Ag2S layer. Oxidative formation of the first Ag2S monolayer occurs by a kinetically facile two-electron, two-step mechanism, involving the one-electron oxidative adsorption of HS- (Ag + HS- ⇌ Ag−SH + e-) followed by a one-electron oxidative phase transition to yield a complete Ag2S monolayer (Ag−SH + Ag + OH- ⇌ Ag2S + H2O + e-). An irreversible wave corresponding to the formation of a second monolayer of Ag2S in a single two-electron step (2Ag + HS- + OH- ⇌ Ag2S + H2O + 2e-) is voltammetrically resolved at slow scan rates (<25 mV/s). Coulometric analysis of the voltammetric data demonstrates that the quantity of electricity (∼164 μC/cm2) consumed during the formation of the first and seco...
Three-spin measurements in pp-->pp at 730 MeV.

We have measured 14 spin observables for {ital pp} elastic scattering at 730 MeV and extracted the isospin-one amplitudes directly from the data. These new data complete the 730-MeV data set to the same standard as the 580-, 650-, and 800-MeV data.
The transmission loss of double expansion chamber mufflers with unequal size chambers

Abstract The double expansion chamber muffler is a commonly used silencing element in duct noise applications. The transmission loss for the case of equal size chambers is known and easily calculated. A closed form expression for the transmission loss for the case of chambers of unequal length and area is presented here. It is also shown that significant tuning benefits result with chambers of unequal size. For evenness of response, with a minimum passband, chamber length ratios of 2:1 and connecting tube lengths equal to the shortest chamber are superior.
Gestational Weight Gain, Early Pregnancy Maternal Adiposity Distribution, and Maternal Hyperglycemia

To estimate the effects of gestational weight gain (GWG), central adiposity and subcutaneous fat on maternal post-load glucose concentration, pregnant women [n = 413, 62% black, 57% with pregravid body mass index (BMI) ≥25] enrolled in a cohort study at ≤13 weeks gestation. GWG was abstracted from medical records. In a sub-sample of women (n = 214), waist circumference (WC), and biceps and triceps skinfold thicknesses were measured at enrollment. At 24-28 weeks gestation, post-load glucose concentration was measured using a 50-g 1-h oral glucose tolerance test. After adjustment for pre-pregnancy BMI, age, parity, race/ethnicity, smoking, marital status, annual family income, education, family history of diabetes, and gestational age of GDM screening, each 0.3-kg/week increase in weight in the first trimester was associated with a 2.2 (95% CI 0.1, 4.3)-mg/dl increase in glucose concentration. Each 8.6-mm increase in biceps skinfold thickness and each 11.7-mm increase in triceps skinfold thickness was associated with 4.3 (95% CI 0.2, 8.5)-mg/dl increase in maternal glucose, independent of BMI and other confounders. Neither GWG in the second trimester nor WC at ≤13 weeks was significantly associated with glucose concentration after confounder adjustment. Independent of pre-pregnancy BMI, high early pregnancy GWG and maternal subcutaneous body fat may be positively associated with maternal glucose concentrations at 24-28 weeks.
Prostaglandin effect on the physical properties of gastric mucus glycoprotein and its susceptibility to pepsin.

Abstract The effect of 16, 16-dimethyl prostaglandin E2 (DMPGE2) on gastric mucus glycoprotein viscosity, permeability to hydrogen ion and degradation by pepsin was investigated. Preincubation with DMPGE2 produced a marked enhancement in the glycoprotein viscosity. The increase was concentration dependent and at 2.6 × 10−5M DMPGE2 reached a value of 178%. Permeability measurements revealed that 2.6 × 10−7M DMPGE2 increased the retardation ability of the glycoprotein to hydrogen ion by 10%, while 22% increase was obtained with 2.6 × 10−4M DMPGE2. The results of peptic activity assay showed that DMPGE2 had no inhibitory effect on the rate of glycoprotein proteolysis, and actually a small stimulatory influence was consistently observed. The results suggest that prostaglandins beneficially effect the physical properties of mucu glycoprotein which are considered do be essential for the protective function of gastric mucus.
One-Dimensional Time-Dependent Modeling of GATE Cumulonimbus Convection.

Abstract A one-dimensional time-dependent cumulonimbus model is designed that, unlike in previous one-dimensional models, simulates cloud-top heights, vertical velocities, and water contents that are reasonably consistent with those observed in real convective cores. The model successfully simulates deep tropical oceanic cumulonimbus with results that are in agreement with aircraft observations of vertical velocity, observations of radar reflectivity, and three-dimensional model simulations. These results are achieved by improving the parameterizations of the following physical processes: vertical mixing through the inclusion of an overturning thermal circulation near cloud top, lateral entrainment by modifying the assumed shape of the cloud, initiating convection with sustained boundary-layer forcing that resembles the lifting by gust fronts associated with tropical oceanic cumulonimbus, and making the pressure perturbation internally consistent with the horizontal distribution of vertical velocity in th...
Community arts facilities

Abstract The rapid growth of local community art's organizations and their need for appropriate facilities stimulated the incorporation of off-the-shelf research methods to organize a facility development process. With the aid of a demonstration grant from the National Endowment for the Arts, a participatory process was initiated and tested with several communities that identified a need for arts' facilities. Beginning with a series of regional workshops co-sponsored with the NCAIA, North Carolina Art's Council, and North Carolina State University's Community Development Group, members of non-profit arts organizations, elected officials, planners, and architects were initiated into a process that included programme planning, design, and fund raising. Follow-up workshops focused on specific building projects and a staged process that started with assessing community needs, goal setting, building image, exploring site options, space planning, and building evaluation and management as essential ingredients for community arts facilities. The approach focused on self-managed environments where participation occurs in all phases of environmental change.
Ion implantation post-processing of amorphous carbon films

Abstract Ion implantation techniques were used to improve the hardness and wear resistance of sputtered hydrogenated amorphous carbon films and cathodic-arc non-hydrogenated amorphous carbon films. Conventional ion implantation and plasma immersion ion implantation and deposition techniques were used to implant the films with Si, Ti, Hf and W ions of mean energies in the ranges of 28–72 and 3–6 keV, respectively, and doses between 1×1015 and 1×1017 cm−2. Nanohardness measurements demonstrated an increase in the apparent film hardness, depending on the type, kinetic energy, and dose of implanted ions. The effect of the ion dose on the microstructure characteristics of implanted carbon films was studied by Raman spectroscopy. Continuous sliding tests and non-contact profilometry revealed an appreciable increase in the wear resistance of the ion implanted films. Differences in the hardness of implanted films are interpreted in terms of microstructural changes caused by competing mechanisms responsible for film densification, irradiation damage and increase of tetrahedral (sp3) bond configurations. It is shown that, under certain conditions, ion implantation post-processing techniques may significantly improve the nanohardness and sliding wear resistance of amorphous carbon films.
Modeling of collaborative design based on Colored Petri nets

This paper is focus on the collaborative design, which is an important process to enterprise. In a manufacture system, a good method can be captured to model the process of collaborative design. But the present process modeling techniques are not sufficient to model the process, which is are IDEF, UML and ARIS. Colored Petri nets is proposed to model the whole process of the collaborative design. The process of collaborative design is a dynamic process and the colored Petri nets can describe the process. The allocation of task, the conflict resolution and other processes are all expressed in the model. The result suggests that the model is suit to express the process of design and it is good to know the whole process of collaborative design. By doing it, the system can be realized successfully.
Unsteady delta-wing flow computation using an implicit factored Euler scheme

The conservative unsteady Euler equations for the flow relative motion in the moving frame of reference are used to solve for the steady and unsteady flows around sharp-edged delta wings. The resulting equations are solved by using an implicit approximately-factored finite-volume scheme. Implicit second-order and explicit second- and fourth-order dissipations are added to the scheme. The boundary conditions are explicitly satisfied. The grid is generated by locally using a modified Joukowski transformation in cross-flow planes at the grid chord stations. The computational applications cover a steady flow around a delta wing whose results serve as the initial conditions for the unsteady flow around a pitching delta wing about a large angle of attack. The steady results are compared with the experimental data and the periodic solution is achieved within the third cycle of oscillation.
Complexity classes and theories of finite models

LetL $$ \subseteq $$ Σ* be accepted in timef(n) by a nondeterministic Turing machine. Then there is a monadic existential second-order sentence σ in the language of + such that for everyx∈Σ*,x∈L if and only if a certain structureU of cardinalityf(|x|) satisfies σ. It follows that ifL is accepted in nondeterministic timen d, d a natural number, then there is a sentence whose relational symbols ared-ary or less, whose finite spectrum isL.
Erythrocyte Ascorbate Recycling: Antioxidant Effects in Blood

Ascorbic acid is an important antioxidant in human plasma, but requires efficient recycling from its oxidized forms to avoid irreversible loss. Human erythrocytes prevented oxidation of ascorbate in autologous plasma, an effect that required recycling of ascorbate within the cells. Erythrocytes had a high capacity to take up dehydroascorbate, the two-electron oxidized product of ascorbate, and to reduce it to ascorbate. Uptake and conversion of dehydroascorbate to ascorbate was saturable, was half-maximal at 400 microM dehydroascorbate, and achieved a maximal intracellular ascorbate concentration of 1.5 mM. In the presence of 100 microM dehydroascorbate, erythrocytes had the capacity to regenerate a 35 microM ascorbate concentration in blood every 3 min. Ascorbate recycling from DHA required intracellular GSH. Depletion of erythrocyte GSH by more than 50% with diamide did not acutely affect the cellular ascorbate content, but did impair the subsequent ability of GSH-depleted cells to recycle dehydroascorbate to ascorbate. Whereas erythrocyte ascorbate recycling was coupled to GSH, an overwhelming extracellular oxidant stress depleted both ascorbate and alpha-tocopherol before the GSH content of cells fell appreciably. Recycled ascorbate was released from cells into plasma, but at a rate less than one tenth that of dehydroascorbate uptake and conversion to ascorbate. Nonetheless, ascorbate released from cells protected endogenous alpha-tocopherol in human LDL from oxidation by a water soluble free radical initiator. These results suggests that recycling of ascorbate in erythrocytes helps to maintain the antioxidant reserve of whole blood.
The contribution of tourism to micro and small enterprise growth.

Tourism is an increasingly important economic sector in many developing countries. In Kenya, it represents the second greatest contribution to gross domestic product (GDP) after agriculture. Data from a survey of 449 micro and small enterprises (MSEs) in coastal Kenya were used in a modified Evans growth model to examine the contribution of tourism to the growth of farm and non-farm MSEs. The authors also examined the influence of entrepreneur and business characteristics on the growth of farm and non-farm MSEs along the Kenyan Coast. The age of the business, business income, marital status, number of employees and form of business organization were found to influence MSE growth significantly. Tourist spending and activities were also found to have a significant effect on MSE growth. The results have implications for the role of tourism in economic development, small business growth and poverty alleviation.
Evaluation of Dimethylpolysiloxane Fluids as Vehicles for Various Pharmaceuticals I: Effect on Stability and Dissolution of Aspirin

The physicochemical effects of dimethylpolysiloxane fluids as vehicles for aspirin on its stability and release characteristics were evaluated. Aspirin was extraordinarily stable in the silicone fluids. No decomposition was noted during 8 weeks of storage at 4 and 26°, and less than 0.5% degradation was detected after 8 weeks of storage at 45°. Moreover, the dissolution patterns of aspirin suspensions in the silicone fluids appeared to be quite satisfactory as compared with that of plain aspirin powder.
Melanoma inhibits macrophage activation by suppressing toll-like receptor 4 signaling.

Background Activated macrophages defend against tumors by secreting cytokines to recruit secondary immune cells, presenting antigen to T cells, and by direct tumor cytotoxicity. Peritoneal macrophages harvested from melanoma-bearing mice are less cytotoxic to melanoma cells, and produce less superoxide, nitric oxide, and tumor necrosis factor-α (TNF-α) than those from nontumor-bearing mice. Similar impairment of macrophage activation occurs in vitro using media harvested from cultured melanoma cells. Stimulation of Toll-like receptor 4 (TLR-4) activates macrophages and results in the release of TNF-α. We hypothesized that melanoma inhibits macrophage activation by suppressing TLR-4 signaling. Study design Melanoma conditioned media (MCM) was generated from B16 melanoma cells. Peritoneal macrophages from TLR-4 competent or TLR-4 incompetent mice were exposed to control or MCM for 24hours; then stimulated with lipopolysaccharide. TNF-α secretion, TNF-α mRNA production, nuclear factor-κB (NF-κB) activation, and TLR-4 surface expression were measured. Results Peritoneal macrophages exposed to MCM produced considerably less TNF-α in response to stimulus than controls (691 pg/mL versus 2,066 pg/mL, p Conclusions Melanoma inhibits macrophage activation by suppressing TLR-4 signaling downstream of the TLR-4 receptor.
New Indications for Already‐Approved Drugs: An Analysis of Regulatory Review Times

A survey of the U.S. pharmaceutical industry was conducted to obtain data on the length of the review process for supplemental indications of already-approved new chemical entities (NCEs). Responses were received from 51 firms and covered supplemental indications of 348 NCEs that were approved during 1963 to 1988. Since extensive toxicity and safety evaluation would generally not be required for supplemental indication reviews, one would expect supplemental indications, on average, to be reviewed more quickly than applications for the associated original indications. The mean +/- standard deviation review time for the 172 supplemental indications in the sample is 21.5 +/- 18 months; the average review time for the associated 94 original indications is 23.5 +/- 18 months. The difference in average review times is not statistically significant. Analysis of review times for indications grouped by Food and Drug Administration (FDA) reviewing division showed a statistically significant difference between supplemental and associated original indication review times only in the cardio-renal division. In that division, average review times were longer for supplemental indications (25.6 vs. 19.3 mo; P less than .05). Analysis of time trends showed a significant increase in average supplemental indication review time for 1985 to 1988 approvals relative to the average associated original indication review time (P less than .01) and to average supplemental indication review time for earlier time periods (P less than .01). These results suggest the need for a close examination of the supplemental indication review policy of the FDA.
Metaplastic Breast Carcinomas are Enriched in Markers of Tumor Initiating Cells and Epithelial to Mesenchymal Transition

Metaplastic breast carcinomas constitute a distinct aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition toward spindle, chondroid, or osseous cell types. During tumorigenesis, epithelial to mesenchymal transition promotes invasion and metastasis and has been linked to the presence of stem cells. We hypothesized that metaplastic carcinomas may express epithelial to mesenchymal transition markers and may be enriched in tumor-initiating cells specifically in the non-glandular metaplastic elements. In 27 primary metaplastic carcinomas of the breast we tested the expression of epithelial to mesenchymal transition inducers ZEB1 and E-cadherin and the presence of tumor-initiating cells by using aldehyde dehydrogenase-1 (ALDH-1) and CD44(+)/CD24(-/low) immunohistochemistry. Of the 27 metaplastic carcinomas, 20 (74%) had squamous and/or spindle areas and 7 (26%) had heterologous elements (6 chondroid and 1 osseous). ALDH-1-positive and CD44(+)/CD24(-/low)-expressing cells were detected in the non-glandular metaplastic components (Fisher's exact, P=0.0017). E-cadherin expression was reduced or absent (aberrant) in all metaplastic components whereas it was normal in the glandular areas. On the contrary, overexpression of ZEB1 was detected in 41% (11 of 27) of the non-glandular, metaplastic components, and in none of the glandular areas. The presence of tumor-initiating cells, aberrant E-cadherin, and ZEB1 upregulation was associated in over 90% of the spindle areas and heterologous elements (χ(2) test, P<0.05). We provide first in situ evidence that epithelial to mesenchymal transition inducers and tumor-initiating cells are present specifically in the non-glandular components of metaplastic carcinomas.
Modeling the Urban Ecosystem: A Conceptual Framework

In this paper I build on current research in urban and ecological simulation modeling to develop a conceptual framework for modeling the urban ecosystem. Although important progress has been made in various areas of urban modeling, operational urban models are still primitive in terms of their ability to represent ecological processes. On the other hand, environmental models designed to assess the ecological impact of an urban region are limited in their ability to represent human systems. I present here a strategy to integrate these two lines of research into an urban ecological model (UEM). This model addresses the human dimension of the Puget Sound regional integrated simulation model (PRISM)—a multidisciplinary initiative at the University of Washington aimed at developing a dynamic and integrated understanding of the environmental and human systems in the Puget Sound. UEM simulates the environmental pressures associated with human activities under alternative demographic, economic, policy, and environmental scenarios. The specific objectives of UEM are to: quantify the major sources of human-induced environmental stresses (such as land-cover changes and nutrient discharges); determine the spatial and temporal variability of human stressors in relation to changes in the biophysical structure; relate the biophysical impacts of these stressors to the variability and spatial heterogeneity in land uses, human activities, and management practices; and predict the changes in stressors in relation to changes in human factors.
Improved performance and student satisfaction after implementation of a problem-based preclinical obstetrics and gynecology curriculum.

Objective This study was undertaken to assess student performance and satisfaction as a preclinical obstetrics and gynecology course changed from a didactic to a problem-based format. Study design We prospectively compared examination scores and course evaluations given to 162 second-year medical students over 4 years: 2 years before and 2 years after the curricular change, to assess student performance and satisfaction with learning. We used analysis of variance for the analysis of student performance and likelihood-ratio test for analysis of student satisfaction. Results Mean examination scores increased from 79.1% to 84% after implementation of the problem-based curriculum (P Conclusion Students' satisfaction and performance in a preclinical obstetrics and gynecology course improved significantly when problem-based learning methods were introduced.
Speech and sensibility: Levinas and Habermas on the constitution of the moral point of view

For Habermas, a moral point of view is based in the procedural requirements of our linguistic competence. For Levinas, it is the way in which we find ourselves related in speech to the face of the other that we find ourselves obliged to the other. But these differing conceptions of the moral significance of language need not be seen as opposed to each other. Rather, they can be conceptualized as complimentary accounts of the ways in which a moral point of view onto life is inextricably bound up for us with our capacities as linguistic creatures. While Habermas enables us to see the importance of language as a rule-governed social practice for the constitution of a moral point of view, Levinas draws our attention to the way in which the moral significance of language so conceived lies in a form of sensibility, a sensible “exposure” or “vulnerability” to the other person, older than language itself. Appropriately coordinated, these two perspectives give us a more adequate understanding than either can on its own of the central place of language in our lives as moral agents.
Microsomal ethanol-oxidizing system (MEOS): purification and properties of a rat liver system free of catalase and alcohol dehydrogenase.

Abstract A separation of the microsomal ethanol-oxidizing system (MEOS) from alcohol dehydrogenase (ADH) and catalase in rat liver microsomes is described. After solubilization of microsomes, ADH and catalase were eluted by DEAE-cellulose chromatography with the hemoglobin containing fraction, whereas MEOS activity was recovered separately. The oxidation of ethanol to acetaldehyde required O2 and NADPH, and was partially inhibited by CO. The fractions exhibiting MEOS activity contained cytochrome P-450, NADPH-cytochrome c reductase and phospholipids. These three components also increased in total microsomes after chronic ethanol consumption and may play a role in the associated enhancement of MEOS activity.
HOW DO BACTERIA DECIDE WHERE TO DIVIDE

Following the establishment of the division site, the cell must specify the plane of division. In globular or cuboid bacteria, several possible orientations of the division septum are compatible with the production of two daughter cells of the same size and shape. In these cases, the pattern of division plane selection determines the architecture of the arrays of progeny cells that often remain associated with each other after division is completed. In chain-forming organisms, the plane of division is approximately the same in each division cycle (-x-x-x-). However, in many bacterial species, the orientation of the division septum alternates between planes that lie at right angles to each other. Interestingly, this includes E. coli rodA mutant cells that grow as spheres (Donachie et al. 1995xDonachie, W.D, Addinall, S, and Begg, K. Bioessay. 1995; 17: 569–576Crossref | PubMedSee all ReferencesDonachie et al. 1995). In these cases, one might expect that the x, y, and z planes would be selected at random since they are topologically equivalent. Instead, there is a rigid selection of certain orientations. In some species, such as Lampropedia (Murray 1984xSee all ReferencesMurray 1984), only two of the three possible planes are used, in an alternating sequence (-x-y-x-y-). This leads to formation of large square planar arrays of cells. In contrast, in organisms such as Sarcinae (Canale-Parola 1970xCanale-Parola, E. Bacteriol. Rev. 1970; 34: 82–97PubMedSee all ReferencesCanale-Parola 1970), cells are organized into three-dimensional cubical 8-celled packets that can only result from the ordered and sequential use of all three of the division planes (-x-y-z-). In each of these examples, the choice of the division plane in each generation determines the two-dimensional or three-dimensional organization of the multicellular arrays of progeny cells that are formed. Essentially nothing has been done to study the mechanisms responsible for these fascinating simple systems of multicellular differentiation.
Glial ensheathment of peripheral axons in Drosophila

The ensheathment of neurons and their axons creates an ion-sensitive microenvironment that allows rapid conduction of nerve impulses. One of the fundamental questions about axonal ensheathment is how insulating glial cells wrap around axons. The mechanisms that underlie insulation of axons in invertebrates and vertebrates are not fully understood. In the present article we address cellular aspects of axonal ensheathment in Drosophila by taking advantage of glial mutants that illustrate a range of phenotypic defects including ensheathment of axons. From the findings of these mutant studies, we summarize that loss of glial cells, defects in glial membrane wrapping, failure of glial migration, and loss of specialized ladderlike septate junctions between ensheathing glial membranes result in axon-glial functional defects. These studies provide a broad perspective on glial ensheathment of axons in Drosophila and key insights into the anatomical and cellular aspects of axonal insulation. Given the powerful genetic approaches available in Drosophila, the axonal ensheathment process can be dissected in great detail to reveal the fundamental principles of ensheathment. These observations will be relevant to understanding the very similar processes in vertebrates, where defects in glial cell functions lead to devastating neurological diseases.
Conference on transport theory firence, Italy, June 7—9, 1978.

Abstract A conference sponsored by the Consiglio Nazionale delle Ricerche, Gruppo Nazionale per la Fisica Matematica (director V. Boffi) and organized by A. Belleni-Morante of the Universita di Firenze and C. Cercignani, Politecnico di Milano, was held in Firenze June 7—9. There were 34 participants, 13 foreign and the remainder Italian, 19 of whom presented papers during the three days. It is a real tribute to the excellence of the presentation and the general enthusiasm kindled by the organizers that the participants by and large were able to forgo the overwhelming temptation to spend their time on sight-seeing and otherwise enjoying the surroundings in what is perhaps the world's most beautiful city. Instead, everyone attended the sessions, argued, discussed, debated and otherwise participated and, presumably, learned.
On laminar free convection stagnation heat transfer from an isothermal cylinder with internal sources-sinks

An analysis of the laminar free convection stagnation heat transfer from an isothermal horizontal cylinder with internal sources and/or sinks within the fluid is presented. Solutions are given for two cases: one in which only the x-direction momentum equation is used and the other in which the two dimensional Navier-Stokes equations are combined into one momentum equation which makes the heat transfer variable θ′(0) and the velocity and temperature profiles to be determined as explicit functions of the Grashof number. Heat transfer results are obtained for Prandtl number of 0.72. Two temperature dependent heat source functions are investigated. It is found that the consideration of the second momentum equation has a moderate but significant effect on the heat transfer results.
THE RIBOSOMES OF THE EXTREMELY HALOPHILIC BACTERIUM, HALOBACTERIUM CUTIRUBRUM.

The ribosomes of Halobacterium cutirubrum, a micro-organism that grows in saturated sodium chloride and probably has an internal concentration of potassium chloride near saturation, exist as 70 s particles when isolated in saturated potassium chloride containing 0·1 M -magnesium chloride at pH 7. These particles are stable in concentrations of magnesium ions as high as 0·4 M . If the potassium ion concentration is below about 4 M , or the magnesium ion concentration below 0·1 M , the ribosomes dissociate into 52 s and 31 s subunits. The requirement by the 70 s particles for potassium ions is specific; in high concentrations of ammonium or caesium ions, many of the ribosomes dissociate into subunits, while in high concentrations of sodium ions, they dissociate and aggregate in a complex way. About 53% of the RNA of the cell is accounted for by the ribosomes, which consist of 60% RNA and 40% protein. The estimated molecular weights of the ribosome and its subunits are in the ratio 3 : 2 : 1. At low concentrations of magnesium ions in the absence of potassium ions, the ribosomes lose low molecular weight RNA and up to 75% of their protein, to produce a labile 42 s component and more stable 33 s and 22 s particles, which contain about 80% RNA. It is suggested that the 42 s, 33 s and 22 s components, with molecular weights in the ratio 3 : 2 : 1, represent essentially the RNA moieties of the whole 70 s ribosome and of the 52 s and 31 s subunits respectively, together with some structural protein. Gel electrophoresis showed that the proteins which are lost are acidic. It is concluded that in these ribosomes, the stability of the ribonucleoprotein depends on potassium ions which shield negative groups, and on magnesium ions, which provide ionic cross-links between RNA and protein.
290 THE EFFECTS OF EXOGENOUS GLUCAGON ON FETAL METABO-LISM IN THE SHEEP

The effect of exogenous glucagon on fetal and maternal glucose, fructose, insulin and glucagon concentrations was studied in the chronic fetal sheep model. Eight near-term fetuses were infused with glucagon (40 ng/min) for 60 min via a fetal femoral vein catheter. Fetal plasma glucagon increased from 37.66±7.86 (SEM) to 420.50±38.59 pg/ml (p<.001) within 15 min of beginning the infusion, reaching 531.80±117.54 pg/ml (p<.001) by 60 min and returning to the baseline level 60 min after stopping the infusion. Fetal arterial glucose increased from 12.06±0.84 to 15.50±0.68 mg % (p<.0001) after 15 min of infusion (p<.001), and reached a maximum level of 17.18±0.94 mg % by 60 min (p<.001). Fetal arterial plasma insulin was significantly increased within 60 min of infusion (16.45±3.73 to 29.38±4.41 uU/ml, p<.001). Fetal fructose did not change. During the 60 min infusion and postinfusion period, there were no changes in the maternal concentrations. These results, in addition to our previous studies demonstrating an increase in fetal glucagon concentration with prolonged maternal fasting, provide further evidence that glucagon is an important regulator of fetal metabolism.