cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3814: FAK inhibition targets nucleostemin, a nucleolar protein, impacting breast cancer spheroid growth and tumor progression

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that controls cell proliferation and survival downstream of integrin-matrix receptors. However, under deprivation of anchorage, FAK translocates to the nucleus. The nucleolus, a non-membrane structure within the nucleus, is important in the control of ribosome biogenesis, regulates the sequestration of nuclear proteins, and increased nucleolar size is a marker of aggressive tumors. Nucleostemin, a nucleolar-localized protein, acts to modulate cell cycle progression and anchorage-independent cell growth. Although many drugs have low efficacy on tumor cells cultured in suspension, nanomolar small molecule FAK inhibitor (PF-271 or PND-1186) addition can prevent anchorage-independent growth of tumor cells as spheroids through mechanism(s) that remain unresolved. Here, we show that pharmacological FAK inhibitor (FAK-I) treatment or kinase-dead (KD) FAK re-expression analyses reduced breast cancer (MDA-MB-231 and 4T1-L) anchorage-independent cell growth with a G0/G1 cell cycle block. This was associated with a specific decrease in nucleostemin protein levels. As FAK-KD forms a complex with nucleostemin, and proteasome inhibitor treatment increased nucleostemin levels in FAK-KD cells, FAK-KD may function as a scaffold to facilitate nucleostemin degradation. In orthotopic breast cancer mouse tumor models, oral FAK-I administration or FAK-KD expression resulted in smaller tumors, decreased Ki67 positive cells, and lower levels of tumor-associated nucleostemin. Ongoing experiments are focused on understanding the molecular mechanisms of FAK nucleolar localization and the regulation of nucleostemin protein levels. Our results point to a novel function of FAK in nucleolar function, spheroid growth, and breast cancer progression. Supported by NIH CA102310 and Susan G. Komen for the Cure (KG111237). Citation Format: Isabelle Tancioni, Sean Uryu, Nichol L. G. Miller, Christine Lawson, Christine Jean, Xiao Lei Chen, David D. Schlaepfer. FAK inhibition targets nucleostemin, a nucleolar protein, impacting breast cancer spheroid growth and tumor progression. [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 3814. doi:10.1158/1538-7445.AM2014-3814
Estrogen and skin: therapeutic options.

As the population of postmenopausal women increases, interest in the effects of estrogen grows. The influence of estrogen on several body systems has been well-documented; however, one area that has not been explored is the effects of estrogen on skin. Estrogen appears to aid in the prevention of skin aging in several ways. This reproductive hormone prevents a decrease in skin collagen in postmenopausal women; topical and systemic estrogen therapy can increase the skin collagen content and therefore maintain skin thickness. In addition, estrogen maintains skin moisture by increasing acid mucopolysaccharides and hyaluronic acid in the skin and possibly maintaining stratum corneum barrier function. Sebum levels are higher in postmenopausal women receiving hormone replacement therapy. Skin wrinkling also may benefit from estrogen as a result of the effects of the hormone on the elastic fibers and collagen. Outside of its influence on skin aging, it has been suggested that estrogen increases cutaneous wound healing by regulating the levels of a cytokine. In fact, topical estrogen has been found to accelerate and improve wound healing in elderly men and women. The role of estrogen in scarring is unclear but recent studies indicate that the lack of estrogen or the addition of tamoxifen may improve the quality of scarring. Unlike skin aging, the role of endogenous and exogenous estrogen in melanoma has not been well established.
Low Dimensional Middle Cubes Are Hamiltonian

Let Qn be the n-dimensional hypercube. If n=2k+1, then the subgraph Mn of Qn induced by the nodes having exactly k or k + 1 ones is called the middle cube of dimension n. A famous conjecture is that Mn is hamiltonian if n>1.
Effect of Ferritic Density and Zinc on Magnetic Properties of Cobalt Ferrite Nanocomposites

Cobalt ferrite nanocomposite was investigated for RF applications. Magnetic nanocomposites were fabricated at different ferritic densities. Cobalt zinc ferrite nanocomposite was also prepared to study the effect of zinc. The size of magnetic nanoparticle was measured by transmission electron microscopy (TEM), while its crystalline structure was characterized by X-ray diffraction (XRD). Toroidal sample was made by compact method. The density of ferrite was controlled by compact pressure and filler loading. The effect of ferritic density and zinc on magnetic properties was analyzed by measuring complex permeability at frequencies up to 1 GHz, using an Agilent Impedance Analyzer, model E4991A. Experimental result showed that the permeability remained almost unchanged at a frequency range from 10 MHz to 1 GHz, while the magnetic loss was less than 0.2. The incorporation of zinc enhanced the magnetic property of cobalt ferrite nanocomposite significantly.
SOLAR ECLIPSE EFFECTS OBSERVED IN THE PLANETARY BOUNDARY LAYER OVER A DESERT

Boundary-layer meteorologicalmeasurements were made before, during, and after theMay 10, 1994 partial (94%) solar eclipse over thedesert at the Atmospheric Profiler Research Facilityat White Sands Missile Range, New Mexico, U.S.A. A largenumber of sensors were located in the middle of theTularosa Basin to measure mean and turbulentquantities and the refractive index structureparameter (Cn2). This event permitted a rareopportunity to measure, examine, and document theeffects upon the atmospheric boundary layer of asudden cut-off and subsequent turn-on of the sun'sradiant energy. At the peak of the eclipse, whichoccurred for more than three hours, all of the heatexchange parameters were affected, the turbulentprocesses were diminished, and the refractive indexstructure parameter decreased dramatically. A time-heightdisplay from the FM-CW radar shows a Kelvin–Helmholtzwave that developed during theeclipse. The results of several analyses arepresented to document and characterize the eclipse-modifiedboundary layer.
Financialization and Structural Change in Commodity Futures Markets

The first decade of the 21 st century has perhaps witnessed more structural change in commodity futures markets than all previous decades combined. Not only have trading volumes and open interest increased markedly, but this time period also saw historic changes in both trading and participants. The available literature indicates that the irrational and harmful impacts of the structural changes in commodity futures markets over the last decade have been minimal. In particular, there is little evidence that passive index investment caused a massive bubble in commodity futures prices. There is intriguing evidence of several other rational and beneficial impacts of the structural changes over the last decade. In particular, the expanding market participation may have decreased risk premiums, and hence, the cost of hedging, reduced price volatility, and better integrated commodity markets with financial markets.
Shared mycorrhizal networks of forest herbs: Does the presence of conspecific and heterospecific adult plants affect seedling growth and nutrient acquisition?

Arbuscular mycorrhizal fungi can colonize the roots of a large number of plant species and individuals, simultaneously creating a network of hyphae connecting the roots of many plants. In this study, I examined the effect of the mycorrhizal network produced by conspecific and heterospecific adult plants on growth and nutrient content of seedlings of Arisaema triphyllum (L.) Schott. and Maianthemum racemosum (L.) Link ssp. racemosum. Seedlings of both plant species were planted so that they could become colonized by the mycorrhizal network or remain uncolonized, and were planted in the presence of a conspecific or heterospecific adult plant. After 2 years of growth, seedlings were harvested and biomass and nutrient content were determined. Biomass of A. triphyllum seedlings was not affected by the identity of the adult plant or colonization by mycorrhizal fungi. Biomass of M. racemosum seedlings was significantly affected by adult plant identity and mycorrhizal colonization. Maianthemum racemosum seedlings...
It Still Isn't Over: Event Boundaries in Language and Perception

The interaction between language and perception networks in the brain can hold the key to the biological bases of language evolution. In language, every sentence is built around a verb, which describes an event. During perception, humans constantly and automatically segment reality into individualized event (verb) units. The cognitive connection between the perceptual segmentation of events and their grammatical expression in language is a novel direction for research into the neurobiology of language, but it may be a key example of the emergence of linguistic structure – grammatical category – from individualized meaning. This article summarizes the current state of this research, and is divided into three parts. The initial overview of cross-linguistic typology of events shows that events and their boundaries are of vital importance to linguistic communication. We then summarize what is known about perceiving and identifying event boundaries in the most well-studied domain, that of visual perception. Here, sign languages provide the link between visual perception and linguistic expression, showing a complex mapping from perceptual and cognitive event segmentation to linguistic structures at the phonology–syntax interface. The last section reviews current evidence for neural bases of event processing, showing that identification of an event boundary (linguistic or perceptual) is used for memory updates, and suggesting the possible role of an event-type universal in the syntactic structure of human languages.
Genetic and Genomic Analyses of RNA Polymerase II-pausing Factor in Regulation of Mammalian Transcription and Cell Growth

Many mammalian genes are occupied by paused RNA polymerase II (pol II) in the promoter-proximal region on both sides of the transcription start site. However, the impact of pol II pausing on gene expression and cell biology is not fully understood. In this study, we used a Cre-Lox system to conditionally knock out the b subunit of mouse negative elongation factor (Nelf-b), a key pol II-pausing factor, in mouse embryonic fibroblasts. We found that Nelf-b was associated with the promoter-proximal region of the majority of expressed genes, yet genetic ablation of Nelf-b only affected the steady-state mRNA levels of a small percentage of the Nelf-b-associated genes. Interestingly, Nelf-b deletion also increased levels of transcription start site upstream transcripts at multiple negative elongation factor-associated genes. The direct target genes of Nelf-b were highly enriched with those involved in the control of cell growth and cell death. Correspondingly, Nelf-b knock-out mouse embryonic fibroblasts exhibited slower progression from quiescence to proliferation, as well as in a cycling cell population. Furthermore, Nelf-b deletion also resulted in increased apoptosis. Thus, the genetic and genomic studies provide new physiological and molecular insight into Nelf-mediated pol II pausing.
Monte Carlo simulation of stored energy driven interface migration

The linear relationship, V = μF where V is the interface velocity, μ is the mobility and F is the driving force is captured only under restricted conditions in conventional Monte Carlo simulations of recrystallization that use a bulk deformation stored energy term in the energy Hamiltonian. In this paper, the migration of an interface driven by a difference in the stored energy of deformation across the interface is simulated using a Monte Carlo approach where the stored energy of deformation is represented as the surface energy of cells/subgrains formed by dynamic recovery during deformation. The interface migration velocity is calculated as a function of the driving force as well as the interface mobility. The simulations capture the linear relationship between interface velocity and driving force for constant interface mobility, and also between interface velocity and mobility for constant driving force, assuming that there is no recovery of the subgrain structure in the bulk of the material during interface migration, and the lattice temperatures are high enough to prevent the locking of the interface in positions of local energy minima. In the presence of simultaneous recovery by subgrain growth in the bulk, the driving force across the interface gradually decreases during interface migration, causing a decrease in the interface velocity. The relevance of these results to mesoscale modelling of recrystallization is discussed.
Hollow needle tissue insertion force model

Abstract In this study, a mechanistic approach using elementary cutting tool (ECT) edges of varying inclination and normal rake angles is demonstrated to be capable to predict hollow needle insertion force. A needle force model is developed and validated for the specific case of 11 gauge two-plane symmetric needles. Blades of varying inclination and rake angles are inserted into bovine liver to determine the specific force of initial tissue cutting for the given edge geometry; this information is applied to the ECT force model which is validated against experimental force results of hollow needles inserted into bovine liver.
Selective Formation of a Symmetric Sc3N@C78 Bisadduct: Adduct Docking Controlled by an Internal Trimetallic Nitride Cluster

In this paper we report a regioselective Bingel−Hirsch reaction of Sc3N@C78 yielding a single mono- and a dominate bis-ethyl malonate derivative for the first time. The Cs-symmetric monoadduct 1 and C2v-symmetric bisadduct 2 were isolated by HPLC and characterized by MS, UV−vis, and NMR spectroscopy. The symmetric bisadduct 2 clearly demonstrate the remarkable regioselectivity control exerted by the encapsulated Sc3N cluster. We have employed a LUMO electron density surface computational approach to predict multiadduct docking sites on the ellipsoidal fullerene cage surface.
Interaction of the Poliovirus Receptor CD155 with the Dynein Light Chain Tctex-1 and Its Implication for Poliovirus Pathogenesis

The cellular receptor for poliovirus CD155 (or PVR) is the founding member of a new class of membrane-associated immunoglobulin-like proteins, which include the mouse tumor-associated antigen E4 (Tage4) and three proteins termed "nectins." Using a yeast two-hybrid screen we have discovered that the cytoplasmic domain of CD155 associates strongly and specifically with Tctex-1, a light chain of the dynein motor complex, the latter representing the major driving force for retrograde transport of endocytic vesicles and membranous organelles. We confirmed the interaction biochemically and by co-immunoprecipitation, and we mapped the Tctex-1 binding site to a SKCSR motif within the juxtamembrane region of CD155. Tctex-1 immunoreactivity was detected in mouse sciatic nerve and spinal cord (two tissues of central importance for poliovirus pathogenesis) in punctate, possibly vesicular, patterns. We propose that the cytoplasmic domain may target CD155-containing endocytic vesicles to the microtubular network. Neurotropic viruses like poliovirus, herpesvirus, rabies virus, and pseudorabies virus all utilize neuronal retrograde transport to invade the central nervous system. Association with Tctex-1 and, hence, with the dynein motor complex may offer an explanation for how poliovirus hijacks the cellular transport machinery to retrogradely ascend along the axon to the neuronal cell body.
Convergence of MAP kinase pathways on the ternary complex factor Sap-1a

The serum response element (SRE), which is pivotal for transcriptional up-regulation of the c-fos proto-oncogene, is constitutively occupied by a protein complex comprising the serum response factor and a ternary complex factor (TCF). Phosphorylation of the TCFs Elk-1 and Sap-1a by the ERK and JNK subclasses of MAP kinases triggers c-fos transcription. We demonstrate here that Elk-1 is barely activated by a third subclass of MAP kinases (p38), most likely because the critical residues Ser383 and Ser389 are poorly phosphorylated by p38 MAP kinase. In contrast, the TCF Sap-1a is efficiently phosphorylated by p38 MAP kinase in vitro and in vivo on the homologous residues Ser381 and Ser387. Mutation of these sites to alanine severely reduces c-fos SRE-dependent transcription mediated by Sap-1a and p38 MAP kinase. Thus, Sap-1a may be an important target for mitogens, stress and apoptotic signals to elicit a nuclear response. However, signaling from p38 MAP kinase to Sap-1a or from Sap-1a to the basal transcription machinery does not occur in all cell types nor at promoters other than the c-fos SRE, which may ensure the specificity of signaling.
Chronic cold stress reduces the spontaneous activity of ventral tegmental dopamine neurons

The dopamine (DA) neurons in the ventral tegmental area and medial substantia nigra (VTA/mSN) projecting to the limbic forebrain and prefrontal cortex have long been postulated to play a major role in cognitive and behavioral effects of stress. In this study, the effects of a chronic stressor (prolonged exposure to cold) on the spontaneous activity of DA neurons in the VTA/mSN were examined. Extracellular single-unit recordings of DA neurons were performed in rats following a 17-day continuous exposure to a cold (4°C) environment. Compared to controls, cold-exposed rats displayed 64% fewer spontaneously active DA neurons. The average spike activity (average firing rate, average spikes fired in bursts) of the DA cells that remained active in the cold-exposed rats did not differ significantly from controls. However, a significantly larger proportion of those cells showed excessive burst activity, compared to the DA cell population in controls. These results show that chronic stress can lead to the cessation of spontaneous activity in a subpopulation of VTA/mSN DA cells. These changes may indicate that unlike acute stress, which can potently activate the mesolimbic/mesocortical DA systems, chronic stress leads to an adaptive reduction in the number of active DA cells, perhaps altering the response of these systems to subsequent stressors.
Conductivity fluctuations and the superlinear current-voltage characteristics in one-dimensional disordered systems

Abstract The current-voltage ( I-V ) characteristic of a one-dimensional (1D) specimen in the strong localization regime is considered. The conductivity of such a specimen is a non-self-averaged quantity since its average value is exponentially larger than the typical one. A finite voltage difference introduces energy averaging that leads to the superlinear I-V curve with gigantic mesoscopic fluctuations. The typical current values and the scale of fluctuations with respect to the current and the voltage are obtained.
Observation on Tile Drainage Performance

In arid and semi-arid climates, tile must maintain the plant rootzone as a low-salt environment. Through evapotranspiration, the rootzone serves to concentrate salts in the soil water, and the tile system provides egress for the saline water below that rootzone. "Envelopes" are material placed around tile to improve water movement from the soil into the tile. "Filters" are envelopes having the additional function of excluding loose soil particles that might enter and clog the tile. The need for filters is demonstrated only in alluvial soils. Periodic flushing out of tile appears to be an alternative to using filters. Materials clogging tile lines have been in the D\D50\N size range of 0.06 mm to 0.12 mm. Satisfactory filter design criteria are based on the standard deviation of normally distributed particle sizes in a large sample, and the well established filter to aquifer ratio. For the size materials that have been found to clog tile lines, filters with D\D50\N = 1.0 mm and σ ≥ 1.0 mm are desirable. A technique to protect tile lines during "subbing-in" and to lessen envelope requirements is discussed.
A processor-time-minimal design for 3D rectilinear mesh algorithms

The paper, using a directed acyclic graph (dag) model of algorithms, investigates precedence constrained multiprocessor schedules for the nx×ny×nz directed rectilinear mesh. Its completion requires at least nx+ny+nz−2 multiprocessor steps. Time-minimal multiprocessor schedules that use as few processors as possible are called processor-time-minimal. Lower bounds are shown for the nx×ny×nz directed mesh, and these bounds are shown to be exact by constructing a processor-time-minimal multiprocessor schedule that can be realized on a systolic array whose topology is either a two dimensional mesh or skewed cylinder.
Glycosylated polyproline II rods with kinks as a structural motif in plant hydroxyproline-rich glycoproteins.

Hydroxyproline-rich glycoproteins (HRGPs) are the major proteinaceous components of higher plant walls and the predominant components of the cell wall of the green alga Chlamydomonas reinhardtii. The GP1 protein, an HRGP of the C. reinhardtii wall, is shown to adopt a polyproline II helical configuration and to carry a complex array of arabinogalactoside residues, many branched, which are necessary to stabilize the helical conformation. The deduced GP1 amino acid sequence displays two Ser-Pro-rich domains, one with a repeating (SP)x motif and the other with a repeating (PPSPX)x motif. A second cloned gene a2 also carries the PPSPX repeat, defining a novel gene family in this lineage. The SP-repeat domains of GP1 form a 100-nm shaft with a flexible kink 28 nm from the head. The gp1 gene encodes a PPPPPRPPFPANTPM sequence at the calculated kink position, generating the proposal that this insert interrupts the PPII helix, with the resultant kink exposing amino acids necessary for GP1 to bind to partner molec...
Tourism, telecommunications and transnational banking.

Abstract The massive growth of international tourism has been paralleled by the increasing globalization of communications and financial services, which in their turn have contributed to the expansion of the tourism industry. This article examines the links between the two and argues that the global tourism infrastructure now forms an important component of international relations. The article attempts to provide a framework for the policy analysis of international tourism and suggests where future research and action are needed.
Dorsal Coloration as an Indicator of Different Life History Patterns for Striped Bass within a Single Watershed of Atlantic Canada

Abstract The striped bass Morone saxatilis spawning within a single river system are generally considered to be members of a single population unit. For some rivers in Canada, however, fishers have reported different-colored groups of striped bass in the watershed during the prespawning and spawning seasons, which suggests the existence of population subgroups. We examined this “colormorph” phenomenon for a striped bass population in the Shubenacadie watershed of Nova Scotia, Canada. Spawning fish had three dorsal coloration patterns: green, which was indicative of fish from the ocean; black, which was indicative of fish that overwinter in a freshwater headwater lake; and mottled, which were fish of unknown origin. Body morphology appeared to be similar among the three groups. Although the age structures of the spawning populations revealed a wider range of age-classes among greenbacked fish, the growth aspects (e.g., length, weight, and length at age) were similar. We estimated that during the prespawnin...
Influence of spark plasma sintering (SPS) processing parameters on microstructure and mechanical properties of nickel

Abstract The influence of variations in the processing parameters employed during spark plasma sintering (SPS) of elemental nickel powders on its microstructure and mechanical properties (i.e., tensile yield strength and ductility) has been investigated in a systematic manner. Bulk polycrystalline nickel samples were fabricated from high purity micron-size powder via SPS for three different pressures (i.e., 50, 65, and 80 MPa) and three different temperatures (i.e., 700, 850, and 1000 °C). These SPS processed nickel samples exhibited an average grain size ranging from 5 to 45 μm, tensile yield strength ranging from 130 to 278 MPa, and ductility ranging from 40% to 60%. The results clearly indicate that as compared to the sintering pressure, the sintering temperature plays a more dominant role in controlling the grain growth and mechanical properties of SPS processed pure nickel. A quantitative Hall–Petch relationship, relating the yield strength to the grain size of SPS processed nickel, has been developed.
Stochastic lot-sizing problem with deterministic demands and Wagner-Whitin costs

In this paper, we consider a two-stage stochastic uncapacitated lot-sizing problem with deterministic demands and Wagner-Whitin costs. We develop an extended formulation in the higher dimensional space that provides integral solutions by showing that its constraint matrix is totally unimodular. We also provide the integral polyhedron of the problem in the original space by projecting the extended formulation to the original space.
PPy/PMMA/PEG-based sensor for low-concentration acetone detection

A polymer pellet-based sensor device comprised of polypyrrole (PPy), polymethyl methacrylate (PMMA) and polyethylene glycol (PEG), its fabrication methods, and the experimental results for low-concentration acetone detection are presented. The design consists of a double layer pellet, where the top layer consists of PPy/PMMA and the bottom layer is composed of PPy/PMMA/PEG. Both sets of material compositions are synthesized by readily realizable chemical polymerization techniques. The mechanism of the sensor operation is based on the change in resistance of PPy and the swelling of PMMA when exposed to acetone, thereby changing the resistance of the layers. The resistances measured on the two layers, and across the pellet, are taken as the three output signals of the sensor. Because the PPy/PMMA and PPy/PMMA/PEG layers respond differently to acetone, as well as to other volatile organic compounds, it is demonstrated that the three output signals can allow the presented sensor to have a better sensitivity and selectivity than previously reported devices. Materials characterizations show formation of new composite with PPy/PMMA/PEG. Material response at various concentrations of acetone was conducted using quartz crystal microbalance (QCM). It was observed that the frequency decreased by 98 Hz for 290 ppm of acetone and by 411 Hz for 1160 ppm. Experimental results with a double layer pellet of PPy/PMMA and PPy/PMMA/PEG show an improved selectivity of acetone over ethanol. The reported acetone sensor is applicable for biomedical and other applications.
Evolution of Microstructures during Laser Surface Cladding of Magnesium Alloy Castings Using Welding Wire

The feasibility of laser repair was studied based on single-/two-layer multi-bead cladding using a continuous wave (CW) 4 kW Nd:YAG laser system and 1.6-mm EZ33A-T5 filler rods for 22.5-mm ZE41A-T5 magnesium alloy sand castings in the machined surface conditions. The results demonstrate the potentiality of repairing magnesium castings using laser surface cladding by wire. Similarly to weld joints, three distinct regions, i.e. clad, partially melted and heat affected zones are observed in the laser-clad beads. The microstructures in these zones and their evolutions are discussed in details.
Magnetically guided orotracheal intubation.

Objective To describe a novel endotracheal intubation technique, magnetically guided intubation (MGI), and its rate of success in inexperienced medical students and interns using an airway mannequin model. Methods This was a prospective, descriptive study of 25 medical students and interns participating in an introductory course on emergency medicine without prior experience in human orotracheal intubation. Magnetically guided intubation consists of a strong external magnet placed over the cricothyroid membrane to guide the introduction of a standard endotracheal tube containing a stylet with a magnetized tip. An airway mannequin was placed in a rigid cervical spinal collar to increase the difficulty of the intubation, and each student performed two sequential intubation attempts using MGI. The proportions of successful intubations and the time to complete intubation were determined. Descriptive statistics were used to describe point estimates and 95% confidence intervals for means and proportions of continuous and categorical data, respectively. Results Of 25 participants, 19 were students and six were interns. Their mean age was 27 years, and 76% were male. The overall proportion of successful intubations using MGI was 80% (95% CI = 69% to 91%). Of 24 intubations, 48% were attempted without visualization of the vocal cords; 67% were successful (95% CI = 46% to 87%). The mean time required to complete intubation was 17.0 seconds (95% CI = 14.5 to 19.5 seconds). Conclusions A novel method of orotracheal intubation using magnetic guidance is described as achieving a high rate of successful intubations when performed by inexperienced intubators.
Comparison of the release of [3h]dopamine from isolated corpus striatum by amphetamine, fenfluramine and unlabelled dopamine

Amphetamine-induced release of previously accumulated [3H]dopamine ([3H]DA) was compared to the release of [3H]DA produced by unlabelled DA and fenfluramine. Like unlabelled DA, amphetamine was more potent than fenfluramine in releasing [3H]DA in all tissue preparations (untreated, pargyline-treated, and pargyline- and reserpine-treated corpus striatal slices). In tissue treated with both reserpine and pargyline, benztropine greatly reduced the efflux of [3H]DA produced by amphetamine and unlabelled DA but had only a slight effect on fenfluramine-induced release of [3H]DA. In the same tissue preparation, Q10 values for the release of [3H]DA produced by 3 X 10(-7) M amphetamine (1.8) and 3 X 10(-6) M unlabelled DA (1.7) were similar to that for the spontaneous release of [3H]DA (1.7). However, when the concentrations of amphetamine and unlabelled DA were increased to 10(-4) M, the Q10 values for the release of [3H]DA were diminished at the lower temperatures. These results suggest that amphetamine may release [3H]DA by two mechanisms: (1) by accelerated exchange diffusion due to its use of the DA uptake carrier to enter into neurons (this would predominate at low concentrations of amphetamine), and (2) by passive entrance into neurons and displacement of [3H]DA from binding sites (this would predominate at high concentrations of amphetamine).
Laser nephelometric quantitation of antithrombin-III (AT-III) development of a new assay

Abstract Antithrombin-III (AT-III) concentration in normal healthy volunteers and in an out-patient population was determined by a radial immunodiffusion (RID) and by a laser nephelometric technique, developed in our laboratory. In 43 normal individuals tested, the mean AT-III concentration by laser nephelometry was 24.1 ± 3.3 mg/dL or 108 ± 13% normal human plasma pool (NHP). The coefficient of variation (CV) of the assay was in the order of 7–10% and there was a good correlation (r=0.81) between RID and laser nephelometric method. Some developmental aspects of the laser nephelometric procedure and its advantages over the RID method are discussed.
Historicism, Formalism, and “Tintern Abbey”

This article responds to Marjorie Levinson's groundbreaking historicist study Wordsworth's Great Period Poems. Beginning with a reading Wordsworth's “Tintern Abbey,” I give a different account of how we might approach the politics of Wordsworth's poetry – namely, by acknowledging Wordsworth's exploration of the interconnection between poetic and institutional forms. I relate this account to several themes that I explore in my own writing on Romantic literature and the history of secular institution-building and penal reform; I close by considering how my arguments depart from recent, competing accounts of literary form.
Treatment of angina pectoris with catron (JB516).

Abstract Catron (JB516), a monoamine oxidase inhibitor, appears to be an antianginal agent which has the combined qualities of effectiveness and low toxicity. It is worthy of extensive trial.
A New Synthetic Route to Soluble Polyquinolines with Tunable Photophysical, Redox, and Electroluminescent Properties

A new monomer bearing dialkyl groups, 3,3‘-dinonanoylbenzidine, when copolymerized with diacetyl monomers gave six new alternating conjugated copolymers, poly(2,2‘-arylene-4,4‘-bis(4-alkylquinolines))s, which are soluble in organic solvents. The thermal, electrochemical, photophysical, and electroluminescent properties of the new polyquinolines varied with the arylene linkage, including p-phenylene, 4,4‘-biphenylene, stilbene, 5,5‘-bithienylene, bis(thienyl)vinylene, and 3,7-phenothiazinylene. The new conjugated polymers combined high glass transition temperature (110−254 °C) with quasi-reversible electrochemical reduction from which 2.72−3.00 eV electron affinities were estimated. The optical band gap varied from 2.19 to 2.86 eV whereas the photoluminescence emission maximum varied from blue-green (477 nm) to deep red (646 nm). Some of the new polymers with alternating donor−acceptor architecture showed strong intramolecular charge transfer. Electroluminescence of moderate brightness (up to 209 cd/m2) wa...
WE-C-BRB-09: Development of a GPU-Based Monte Carlo Dose Calculation Package for Proton Radiotherapy

Purpose:Monte Carlo(MC) simulation is considered to be the most accurate method for proton therapydose calculation. However, the long computation time limits it from routine clinical applications. Recently, graphics processing units (GPUs) have been widely used to accelerate computationally intensive tasks in radiotherapy. The purpose of this project is to develop a fast MCdose calculation package, gPMC, for protondose calculation on a GPU. Methods: gPMC supports proton transport in the energy range of 0.5∼300 MeV. Proton transport is modeled by the Class II condensed history simulation scheme with continuous slowing down approximation. Ionization,elastic and inelastic proton nucleus interactions are considered. Energy straggling and multiple scattering are modeled. Secondary electrons and charged nuclear fragments are not transported and their energies are locally deposited. Secondary protons are stored in a stack and transported after the primary protons finish, while secondary neutral particles are neglected. gPMC is implemented on GPU under the CUDA platform with each GPU thread responsible for the transport of a single proton. A high performance random number generator and hardware linear interpolation are utilized. Results: We have validated gPMC in various cases including homogeneous phantoms with different materials and a phantom of a half slab geometry. A mono‐energetic mono‐directional proton beam is used. Good agreements between results from gPMC and Geant4 are observed, and the gamma passing rate for 3%/3mm criterion is over 99.9% in the region with dose greater than 10% maximum dose. It takes 6.3∼24.1 sec to simulate 10 million source protons depending on the phantoms and the energy. A high efficiency has been achieved compared to the computational time of tens of CPU hours for Geant4. Conclusions: We have developed a GPU‐based MCprotondose calculation package, gPMC. The achieved accuracy and efficiency is promising for clinical applications.
The life course as a theoretical orientation: Sequences of person‐situation interaction1

The life course is proposed as a theoretical orientation concerned with the problems of describing, understanding, generalizing about, predicting, and intentionally changing the course of lives. A life course orientation provides a framework for analyzing the causal and probabilistic structure of the course of experience in individual lives, groups of lives, and lives in general. The life course can be conceptualized as a sequence of person-situation interactions, or as a sequence of behavior-determining, person-determining, and situation-determining processes. This perspective is illustrated through an analysis of the careers of heroin users, and through a critical examination of several common strategies for predicting behavior. The study of lives is distinguished from the study of personality, and the historical and theoretical background for a life course orientation is briefly reviewed.
Isolation, observation, and computational modeling of proposed intermediates in catalytic proton reductions with the hydrogenase mimic Fe2(CO)6S2C6H4

Proposed electrocatalytic proton reduction intermediates of hydrogenase mimics were synthesized, observed, and studied computationally. A new mechanism for H2 generation appears to involve Fe2(CO)6(1,2-S2C6H4) (3), the dianions {[1,2-S2C6H4][Fe(CO)3(μ-CO)Fe(CO)2]2− (32−), the bridging hydride {[1,2-S2C6H4][Fe(CO)3(μ-CO)(μ-H)Fe(CO)2]}−, 3H−(bridging), and the terminal hydride 3H−(term-stag), {[1,2-S2C6H4][HFe(CO)3Fe(CO)3]}−, as intermediates. The dimeric sodium derivative of 32−, {[Na2(THF)(OEt2)3][32−]}2 (4) was isolated from reaction of Fe2(CO)6(1,2-S2C6H4) (3) with excess sodium and was characterized by X-ray crystallography. It possesses a bridging CO and an unsymmetrically bridging dithiolate ligand. Complex 4 reacts with 4 equiv. of triflic or benzoic acid (2 equiv. per Fe center) to generate H2 and 3 in 75% and 60% yields, respectively. Reaction of 4 with 2 equiv. of benzoic acid generated two hydrides in a 1.7 : 1 ratio (by 1H NMR spectroscopy). Chemical shift calculations on geometry optimized structures of possible hydride isomers strongly suggest that the main product, 3H−(bridging), possesses a bridging hydride ligand, while the minor product is a terminal hydride, 3H−(term-stag). Computational studies support a catalytic proton reduction mechanism involving a two-electron reduction of 3 that severs an Fe–S bond to generate a dangling thiolate and an electron rich Fe center. The latter iron center is the initial site of protonation, and this event is followed by protonation at the dangling thiolate to give the thiol thiolate [Fe2H(CO)6(1,2-SHSC6H4)]. This species then undergoes an intramolecular acid–base reaction to form a dihydrogen complex that loses H2 and regenerates 3.
Structure and Activity of the Flagellar Rotor Protein FliY A MEMBER OF THE CheC PHOSPHATASE FAMILY

Rotating flagella propel bacteria toward favorable environments. Sense of rotation is determined by the intracellular response regulator CheY, which when phosphorylated (CheY-P) interacts directly with the flagellar motor. In many different types of bacteria, the CheC/CheX/FliY (CXY) family of phosphatases terminates the CheY-P signal. Unlike CheC and CheX, FliY is localized in the flagellar switch complex, which also contains the stator-coupling protein FliG and the target of CheY-P, FliM. The 2.5 Å resolution crystal structure of the FliY catalytic domain from Thermotoga maritima bears strong resemblance to the middle domain of FliM. Regions of FliM that mediate contacts within the rotor compose the phosphatase active sites in FliY. Despite the similarity between FliY and FliM, FliY does not bind FliG and thus is unlikely to be a substitute for FliM in the center of the switch complex. Solution studies indicate that FliY dimerizes through its C-terminal domains, which resemble the Escherichia coli switch complex component FliN. FliY differs topologically from the E. coli chemotaxis phosphatase CheZ but appears to utilize similar structural motifs for CheY dephosphorylation in close analogy to CheX. Recognition properties and phosphatase activities of site-directed mutants identify two pseudosymmetric active sites in FliY (Glu35/Asn38 and Glu132/Asn135), with the second site (Glu132/Asn135) being more active. A putative N-terminal CheY binding domain conserved with FliM is not required for binding CheY-P or phosphatase activity.
Differential Regulation of Serum Immunoreactive Luteinizing Hormone and Bioactive Follicle-Stimulating Hormone by Testosterone in Early Pubertal Boys*

The microheterogeneity and bioassayable activity of serum FSH (B-FSH) can be regulated by exogenous GnRH in boys with idiopathic hypogonadotropic hypogonadism and by estrogen in a woman with gonadal dysgenesis, presumably via hormonally mediated changes in the degree of FSH glycosylation. To test the hypothesis that testosterone (T) regulates the circulating forms of B-FSH, we raised the serum T levels of early pubertal boys to adult levels. In this model, high dose T inhibits the pubertal nocturnal augmentation of LH secretion, apparently through decreased GnRH secretion. This model allowed us to test a second hypothesis, that B-FSH is a sensitive indicator of hypothalamic GnRH release. The boys were studied on two consecutive weekends, during which they received either saline (S) or T infusions. Beginning at noon on the study day, after an overnight acclimatization, the boys received either S or T at 33% or 100% of the adult male production rate. Blood was sampled from 2000-0800 at 10-min intervals for ...
THE EFFECTS OF NITROGEN SOURCE AND CONCENTRATION ON THE GROWTH AND MINERAL COMPOSITION OF PRIVET

Nursery crops are fertilized with nitrogen (N) to enhance their growth and appearance, and crop responses to fertilization vary with form of N supplied and with plant species. This experiment, conducted in a greenhouse, examined privet (Ligustrum ibolium L.) growth and composition as affected by three N sources: 100% of the N as nitrate, 100% of the N as ammonium and a 50%–50% mixture of nitrate-N and ammonium-N. Nine different concentrations (in treatments incrementally ranging 0 to 300 mg N/L) of the three N regimes on privet growth and composition were studied in sand culture. After 240 days of treatment, total growth (mass or shoot extension) of privet did not differ among the three N sources. However, growth increased with increased N concentration with maximum growth occurring between 50 and 250 mg N/L. Although root mass did not vary among the N sources during the experiment, privet grown with ammonium nutrition had more blackened, discolored roots than plants grown with nitrate or mixed nutrition;...
Self-concept assessment for young children: Development of a self-report, peer comparison measure☆

Abstract The present investigation concerned the development of the Primary Self-Concept Inventory (PSCI), a group-administered self-report self-concept inventory for children of ages 5 through 8. Replicated analysis of the factor structure of the PSCI data indicated that a seven-component pattern provides an appropriate fit. As a result of this analysis, seven subscales were formed. Acceptable test—retest reliability estimates were obtained for administrations separated by a 6-month interval. On the basis of these results, the PSCI was accepted as a research tool, and recommendations for further investigation of the inventory were made.
A 5-HT3 receptor agonist induces a chloride secretory response in the presence of neural blockade in rat distal colon

Abstract Introduction: Serotonin (5-HT) is a well-described intestinal secretagogue. The 5-HT3 receptor is one of many 5-HT subtypes and is generally accepted to reside at the level of the enteric neuron. We hypothesize that a further subtype of the 5-HT3 receptor may be found on a nonneural cell in rat colon. Methods: Partial-thickness sheets of rat distal colon (n = 9) were mounted in Ussing chambers and short-circuited. The selective 5-HT3 receptor agonist, 2-met-5-HT (50 micromol), was added in the presence or absence of 1 micromol of the neural sodium channel blocker, tetrodotoxin (TTX). Control tissue received no drug. Changes in short-circuit current (Isc), a measure of electrogenic chloride secretion, was measured continuously. Results: Histologic examination of the stripped colon revealed intact mucosa and muscularis mucosa, scant submucosa, and virtually no neural ganglia (HE ANOVA) or TTX alone (p Conclusions: In this in vitro preparation of rat colon, the selective 5-HT3 receptor agonist, 2-met-5-HT, induced a chloride secretory response that was TTX-insensitive. These findings suggest the presence of a nonneural 5-HT3 receptor located at the level of the mucosa. TableMean (+/− SEM) changes in Isc from baseline in microamps/cm 2 MinControl2Met5HT∗2Met5HT + TTX∗TTX5−1.3 ± 0.911.3 ± 2.28.1 ± 3.0−0.3 ± 0.210−1.8 ± 1.912.0 ± 3.37.3 ± 1.9−0.8 ± 0.315−3.3 ± 3.09.3 ± 1.86.7 ± 1.6−0.8 ± 0.430−4.3 ± 4.18.6 ± 1.95.2 ± 1.2−0.9 ± 0.660−5.0 ± 4.35.5 ± 2.12.0 ± 0.8−1.1 ± 0.7∗p
Different mechanisms for inhibition of cell proliferation via cell cycle proteins in PC12 cells by nerve growth factor and staurosporine.

PC12 cells have previously been shown to cease cell division during nerve growth-factor (NGF)-induced differentiation by affecting specific cell cycle proteins. Staurosporine, a protein kinase inhibitor, also causes PC12 cell differentiation, independently of neurotrophins or plasma membrane receptors. We have investigated the relationship of the tumor suppressor protein, p53, and other cell cycle proteins to the antiproliferative effects of NGF and staurosporine in PC12 cells. NGF treatment of PC12 cells stimulated an increase of p53 protein in the nucleus and, more slowly, an increase in total cellular p53 protein. Levels of the cyclin-kinase inhibitor p21/WAF1, cyclin D1, and cyclin G, all downstream transcriptional targets of p53, increased after short times of NGF treatment. Cessation of replication and differentiation occurred more rapidly in defined medium (2 days) than in serum medium (6 days), in correspondence with the more rapid changes in both p53 and p21/WAF1 levels in defined medium (1 hour) than in serum (1 day). Levels of p34cdc2 and p33cdk2 kinase dropped after 6 to 10 days treatment with NGF in serum, close to the time of terminal differentiation. Staurosporine, on the other hand, inhibited DNA replication of PC12 cells in a time- and dose-dependent fashion by affecting cyclin-dependent kinases. Staurosporine had no effect on the protein levels of p53, p21/WAF1, or cyclin G. The kinase activity of both p34cdc2 and p33cdk2 were inhibited in vitro with IC50 values of 20 nM and 75 nM, respectively. In vivo p34cdc2 kinase activity was inhibited within 1 day, before the decrease in the levels of p34cdc2 protein at days 2 to 3. In contrast, in vivo p33cdk2 kinase activity only decreased in concert with protein levels. Although both NGF and staurosporine inhibit DNA replication concomitant with induction of differentiation by affecting the activity of p34cdc2 and p33cdk2, the mechanism of the two agents is quite different. NGF achieves inhibition of activity of these cyclin-dependent kinases by signalling through the TrkA receptor to the tumor supressor protein p53 and then to p21/WAF1. In contrast, staurosporine directly inhibits the activity of p34cdc2 and p33cdk2 by binding to them and also indirectly by alteration of their phosphorylation through other regulatory kinases. J. Neurosci. Res. 49:461–474, 1997. © 1997 Wiley-Liss, Inc.
Multigenic control of immune responses of inbred mice against the terpolymers poly(Glu57Lys38Ala5) and poly(Glu54Lys36Ala10) and linkage withH-2 haplotype

Results of immunizations of recombinant inbred and congenic strains of mice with the random polymers poly(glu57 lys38ala5) or GLA5 and poly(glu54lys36ala10) or GLA10 indicate that there is an association of the responsiveness with theH-2 haplotype. Although the C57BL/6J mice (H-2 b haplotype) are “non responders”, the C57BL/6By originally derived from mice of the same haplotype are responders. The immune response pattern of recombinant strains carrying haplotypes derived by crossing over within theH-2 complex indicate that the responsiveness is under control of anIr gene which maps to the left of theIB subregion. Studies with the backcross mice indicated multigenic control of the responsiveness, with one locus beingH-2 linked and another locus segregating independently ofH-2.