cssi/SciSciGPT-SciSciNet huggingface dataset:
Information and learning commons, faculty and student benefits

Purpose – The purpose of this paper is to examine the benefits of information and learning commons to students and faculty.Design/methodology/approach – Based on the experiences of its author, this paper considers two cases in which Georgia Tech faculty worked with the Georgia Tech Library's East and West Commons to expand their teaching practices and their students' learning and research opportunities. It then discusses the benefits of these activities to students and faculty.Findings – This paper argues that, although information and learning commons are designed primarily to benefit college and university students, these spaces can, with little modification, benefit faculty as well.Originality/value – The idea that information and learning commons benefit students is nothing new. They are explicitly designed for that purpose. But, the idea that information and learning commons might also support college and university faculty teaching and research interests is one that has received little attention in ...
On the possibility to represent effective properties of a material with inhomogeneities in terms of concentration parameters

Abstract It is argued that representation of the effective properties of heterogeneous materials in terms of a single parameter of concentration of inhomogeneities (such as volume fraction or crack density) is generally impossible for mixtures of inhomogeneities of diverse shapes; the exceptions – when this is possible – are identified. Application of such parameters to microstructures of “irregular” microgeometries may lead to various inconsistencies. Instead, the effective constants in such cases can be represented in terms of a “tracking” parameter for a specific process of evolution of a microstructural pattern. These issues are discussed in the context of the elastic and conductive properties.
An ELDOR study at 77 K of the proton environment surrounding the methyl radical in irradiated ammonium acetate crystals

Abstract Two sets of matrix proton lines were observed in the electron-electron double-resonance (ELDOR) spectrum of the methyl radical trapped in ammonium acetate crystals irradiated at 77 K. One of the sets is due to those matrix protons which lie at an average distance of 3.3 A or greater from the unpaired electron. The second set is due to a matrix proton located at an approximate distance of 2.7 A from the unpaired electron on the methyl radical. Comparison of these distances to the corresponding crystallographic orientation and distances shows that the methyl radical does not migrate more than 0.3 A from its position in the undamaged molecule.
Inhibition of protein synthesis results in super-induction of procyclin (PARP) RNA levels.

Abstract Procyclin is an abundant surface antigen found exclusively on the procyclic forms of African trypanosomes. We are interested in the induction of procyclin gene expression during differentiation from bloodstream forms. We find that increased levels of procyclin RNA are evident as early as 15 min after triggering differentiation. The increase in procyclin RNA levels requires the temperature shift from 37°C to 27°C and is aided by addition of the tricarboxylic acid cycle intermediate cis -aconitate. Maximal induction is observed with a combination of three triggers of differentiation: citrate, cis -aconitate and the temperature shift. Protein synthesis does not appear to be required for induction of procyclin RNA during differentiation. In fact, addition of protein synthesis inhibitors results in super-induction of procyclin RNA levels, even under conditions where no induction is normally observed (i.e., at 37°C in the absence of citrate and cis -aconitate). This super-induction was observed with four different protein synthesis inhibitors that affect different stages of translation. Thus, the accumulation of procyclin transcripts may be under the control of a negative regulator whose effective levels are reduced during differentiation from bloodstream to procyclic forms.
Effects of vibronic interaction and autoionization on the photoelectron spectrum of N2O

High‐resolution and high‐sensitivity HeI photoelectron spectra (PES) are reported for the first four valence levels of N2O. The vibrational structure, including many new peaks, is completely assigned for the X 2Π, A 2Σ+, and C 2Σ+ electronic states, and in all three cases excitation of a single quantum of the bending vibration is observed. The bending mode appears as a result of vibronic coupling within and between different electronic states. The Renner–Teller splitting is resolved in the (0,1,0) band of the transition to the X 2Π state. The relative intensities of the vibrational bands in the X 2Π and A 2Σ+ states are compared to the intensities determined from the threshold photoelectron spectra (TPES) of Frey et al. [Chem. Phys. Lett. 54, 411 (1978)]. In both states, autoionization of intermediate neutral states that are nearly degenerate with the molecular ion state to which they decay increases the relative intensities of the higher vibrational bands in the TPES. This resonant autoionization process...
Abstract 3609: Homology structure-based design, synthesis and biological evaluation of a series of novel Axl and Mer kinase inhibitors

Axl and Mer kinases belong to the TAM family that was first identified as a transforming gene in chronic myeloid leukemia. Its intracellular region has the typical receptor tyrosine kinase (RTK) structure and its extracellular domain is similar to cadherin-type adhesion molecules in that it is composed of fibronectin type II and immunoglobulin (Ig) motifs. Axl binds various growth factors, with vitamin K-dependent protein growth-arrest-specific gene 6 (GAS6) being the best studied. Axl is involved in mesenchymal and neuronal development as well as in cell survival, adhesion and blood vessel function. High levels of Axl are found in various tumors, including malignant glioma and metastatic colon, ovarian and breast cancers, and it plays a role in cancer invasion. Recent development of Axl inhibitors suggested that inhibition of Axl activity may be impact both tumor angiogenesis and tumor growth. We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, inhibitors of Axl and Mer kinases. Our initial lead compound was identified via cross-docking experiments utilizing the homology model of Axl kinase and screening of a diverse in-house chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure which has 2 to 6.1 μM inhibition activity to 2-fold improvement in the Axl and Mer kinase activities to 730 nM. As a starting point for further optimization, it was considered that the modest of these series could be improved by introducing a spacer at the aryl piperazine moiety and focused on maximizing the in vitro potency, addressing the SAR and molecular properties. We further explored Leu620, hydrophobic, Gly543, Phe547 and DFG motif sites through scaffold hoping lead to the identification of an electron-withdrawing functional groups lead to the compound HCI-2084 and HCI-2091 which exhibited potent Axl kinase inhibition activity of 7 and 12 nM in Axl kinase assay and 30-50 nM is panel of cancer cell lines. These novel series of compounds were synthesized in two-step procedure via a standard cross-coupling reaction or with various substituted aryl amine derivatives under amination conditions. In a subsequent step we employed Buchwald-Hartwig amination reaction to prepare target molecules. Due to the ready synthesis accessibility, we extensively investigated the SAR improving the RO5, solubility and permeability parameters. The details of these results will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3609. doi:10.1158/1538-7445.AM2011-3609
Remote sensing of the ring current using energetic neutral atoms

Energetic neutral atom images of the storm-time ring current obtained from the ISEE-1 spacecraft provide information for a 'zero-order' global model of the energetic ion distribution. With the assumption of isotropic pressure and magnetostatic, nonconvective pressure balance, the global system of electrical currents driven by the ion pressure can be calculated using Euler potentials for the divergenceless current density. Radial pressure gradients drive azimuthal currents, and azimuthal pressure gradients drive radial currents. The radial currents cause current lines in the inner magnetosphere to close in the ionosphere, forming a partial ring current. The intensities and locations of these field-aligned currents driven into and out of the ionosphere resemble those of the observed Region 2 current system, but not all observed properties of the Region 2 system are reproduced by the zero-order model.
Classifying singularities up to analytic extensions of scalars is smooth

Abstract The singularity space consists of all germs ( X , x ) , with X a Noetherian scheme and x a point, where we identify two such germs if they become the same after an analytic extension of scalars. This is a complete, separable space for the metric given by the order to which jets (=infinitesimal neighborhoods) agree after base change. In the terminology of descriptive set-theory, the classification of singularities up to analytic extensions of scalars is a smooth problem. Over C , the following two classification problems up to isomorphism are then also smooth: (i) analytic germs; and (ii) polarized schemes.
Comparative studies on highly metabolically active histone acetylation

Histone acetate is hydrolyzed rapidly in logarithmically dividing hepatoma tissue culture cells (Jackson, V., Shires, A., Chalkley, R. and Granner, D.K. (1975) J. Biol. Chem. 250, 4856--4863). The phenomenon has been analyzed further in hepatoma tissue culture cells at various stages of the cell cycle, in stationary phase, and in the presence of actinomycin D. We also investigated the phenomenon in Tetrahymena pyriformis macronuclei, bovine thymocytes, and human foreskin fibroblasts. The data suggest that this highly metabolically active histone acetylation while altered in mitotic cells, is independent of the overall rate of cell division, and is only slightly sensitive to actinomycin D. Finally, we conclude that the same general phenomenon is found in both cancerous and normal cells and is apparently common to cells from various stages of the evolutionary scale.
Effects of functionalized fullerenes on bifenthrin and tribufos toxicity to Daphnia magna: Survival, reproduction, and growth rate.

Incorporation of carbon nanomaterials into industrial and consumer products is increasing, yet their impact on aquatic ecosystems alone and in chemical mixtures is largely unknown. Carbon nanomaterials may be found in the aquatic environment as mixtures with pesticides because of their proposed use in agriculture as smart delivery systems and nanosensors. The interaction effects of a functionalized fullerene ([1,2-methanofullerene C60]-61-carboxylic acid) (fC60) at 52.8 µg/L and the hydrophobic pesticides bifenthrin and tribufos were examined. The test organism was Daphnia magna, and response variables included 48-h survival, reproduction (bifenthrin, 70-d; tribufos, 21-d), and 10-d growth. Both pesticides reduced D. magna survival and reproduction (p 0.05). Median lethal concentrations (LC50s), median inhibition concentrations (IC50s) for days surviving, and IC50s for reproduction were 0.86, 0.55, and 0.49 µg/L for bifenthrin; 0.22, 0.39, and 0.77 µg/L for fC60-bifenthrin mix; 6.63, 9.89, and 5.79 µg/L for tribufos; and 9.17, 8.17, and 6.59 µg/L for fC60–tribufos mix. Mixtures did not affect instantaneous growth rate (p > 0.05). These results suggest that fC60 had little effect on pesticide chronic toxicity but influenced acute toxicity. Given the widespread application of nanotechnology, the influence of nanomaterials on environmental contaminants is an important consideration. Thus, our results may be useful in the development and use of nanotechnology in agricultural practices. Environ. Toxicol. Chem. 2010;29:2600–2606. © 2010 SETAC
Optic pathway glioma associated with orbital rhabdomyosarcoma and bilateral optic nerve sheath dural ectasia in a child with neurofibromatosis-1

Neurofibromatosis-1 (NF-1) is a multisystem disorder presenting with a variety of clinical and imaging manifestations. Neural and non-neural tumours, and unusual benign miscellaneous conditions, separately or combined, are encountered in variable locations. We present a 2½-year-old boy with NF-1 who demonstrated coexisting optic pathway glioma with involvement of the chiasm and optic nerve, orbital alveolar rhabdomyosarcoma and bilateral optic nerve sheath dural ectasia.
Linoleic and linolenic acids: their oxidation by normal and diabetic rats.

Summary1. Oxidation of linoleic and linolenic acids, both randomly labeled with C14, to CO2 was compared in a) fasted and glucose-fed normal rats; b) normal and diabetic fed rats; and c) insulin-treated and untreated, fed diabetic rats. 2. Administration of glucose spared oxidation of both linoleic and linolenic acids. 3. Oxidation of linoleic acid by ad lib.-fed diabetic rat exceeded that by similarly fed normal rat. 4. Insulin spared oxidation of polyunsaturated fatty acids in the diabetic rat.
Redefining MicroRNA Targets

Animal microRNAs (miRNAs) guide proteins to repress the translation of target mRNAs via imperfect base pairing between the miRNA and the target. Computational analyses suggest that each miRNA regulates tens or hundreds of targets [1, 2], yet genetic studies usually show that the repression of a few targets plays a physiological role [3-5]. The extent of miRNA-mediated repression (which rarely exceeds 2-fold [1, 2]) is also surprisingly lower than most well-tolerated, intrinsic variations in gene expression [6, 7]. Although miRNA targets are well conserved among closely related species, they differ greatly between more distant animals [8]. The prevailing view is that miRNAs "tune" expression of most of their targets [1, 2]. Here, I propose an alternative hypothesis that could resolve these three paradoxes: many computationally identified miRNA targets may actually be competitive inhibitors of miRNA function, preventing miRNAs from binding their authentic targets by sequestering them. Depending on the prevalence of this type of miRNA:mRNA interaction, this new conception of miRNA regulation could have profound implications on our assumptions about miRNA function.
Paradigms for primary prevention of ovarian carcinoma.

Objective: To provide the clinician with current concepts regarding prevention of ovarian cancer. Specifically, in this review, we provide a rationale for chemoprevention of ovarian cancer, a description of promising chemopreventive agents, and an overview of surgical strategies used in the prevention of ovarian cancer. Data Sources: A computerized search of articles published through December 2001 was performed using the MEDLINE database from the period of 1966 to present. Search terms utilized included ovarian neoplasms, primary prevention, chemoprevention, oral contraceptives, NSAIDs, retinoids, ovariectomy, and tubal sterilization. Additional sources were identified through cross-referencing. Methods of Study Selection: All identified references relevant to prevention of ovarian carcinoma were reviewed. Tabulation, Integration, and Results: Each reference was reviewed to determine the relevant contribution to the fundamental science of ovarian cancer prevention. Particular attention was paid to those studies that offered insight into the development of translational trials in ovarian cancer chemoprevention. Conclusions: Investigation into chemoprevention for ovarian cancer represents a vastly underdeveloped area of research. Continued research efforts toward identification of novel compounds will accelerate the progress of clinical trials in this neglected area of investigation.
Stigma of manic depression: a psychologist's experience.

THE LANCET • Vol 352 • September 26, 1998 1053 and provide a haven for real distress at the worst times of illness. All this requires money as well as new socially inclusive attitudes from the community and its representatives. Mental illness is no respecter of persons. It affects many in society, black and white, young or old, rich or poor. But to be black, poor, and mentally ill is to suffer the most extreme discrimination that society can impose. The UK Disability Discrimination Act 1996 should be widened to encompass social discrimination against people with mental illness, and the Equal Opportunities Commission charged with tackling this last bastion of endemic discrimination. Little has been heard of the UN Commission on Human Rights, Declaration on the Rights of Mentally Ill People adopted in 1991. With the incorporation of the European Convention on Human Rights into UK law, perhaps the UK Government could go one step further and enshrine the rights set out in the Declaration. Those suffering discrimination as a result of mental illness would then have a statute against which to claim protection and redress. Other jurisdictions might then follow. Only a bold move of that sort, demonstrating governments’ real determination to outlaw discrimination against disabled people, will change attitudes to those who have been unjustifiably neglected for so long.
Genome-Wide Association Study of Serum Minerals Levels in Children of Different Ethnic Background

Calcium, magnesium, potassium, sodium, chloride and phosphorus are the major dietary minerals involved in various biological functions and are commonly measured in the blood serum. Sufficient mineral intake is especially important for children due to their rapid growth. Currently, the genetic mechanisms influencing serum mineral levels are poorly understood, especially for children. We carried out a genome-wide association (GWA) study on 5,602 European-American children and 4,706 African-American children who had mineral measures available in their electronic medical records (EMR). While no locus met the criteria for genome-wide significant association, our results demonstrated a nominal association of total serum calcium levels with a missense variant in the calcium –sensing receptor (CASR) gene on 3q13 (rs1801725, P = 1.96 × 10-3) in the African-American pediatric cohort, a locus previously reported in Caucasians. We also confirmed the association result in our pediatric European-American cohort (P = 1.38 × 10-4). We further replicated two other loci associated with serum calcium levels in the European-American cohort (rs780094, GCKR, P = 4.26 × 10-3; rs10491003, GATA3, P = 0.02). In addition, we replicated a previously reported locus on 1q21, demonstrating association of serum magnesium levels with MUC1 (rs4072037, P = 2.04 × 10-6). Moreover, in an extended gene-based association analysis we uncovered evidence for association of calcium levels with the previously reported gene locus DGKD in both European-American children and African-American children. Taken together, our results support a role for CASR and DGKD mediated calcium regulation in both African-American and European-American children, and corroborate the association of calcium levels with GCKR and GATA3, and the association of magnesium levels with MUC1 in the European-American children.
Proton precipitation during the auroral breakup

Abstract Rapid measurements of the spatial and temporal variations of the Balmer beta line of hydrogen in aurorae have been obtained with a meridian-scanning photometer. The data confirm previous spectographic evidence which shows that the pre-breakup 'hydrogen arc' is a stable, weak and diffuse arc of considerable latitudinal extent. This description is consistent with theoretical calculation for the precipitation pattern of low-energy isotropic protons. The photometric data also reveal that the hydrogen emissions participate in the auroral breakup. At that time the H-beta line increases markedly in intensity, becomes spatially discrete, and appears within the bright breakup arc. Such behaviour implies an increase in the proton flux and either a large increase in the energy of the incident protons or a drastic narrowing of their pitch angle distribution. Both effects may occur, but the present data does not provide specific information on pitch angle distributions. On the other hand, the observational evidence from the concurrent behaviour of the other auroral emissions and from other types of measurements indicates that the characteristic energy of the incident protons increases from approx 15 keV to 150 keV during the breakup of an auroral display. The possibility of electron excitation of ambient hydrogen has been re-examined. Taking extreme values for the electron flux, H-beta excitation cross-section and atmospheric hydrogen density, it is possible that up to 40 per cent of the hydrogen emission observed in bright, discrete breakup arcs can be attributed to electron excitation of ambient hydrogen. However, there is insufficient data at this time to determine whether or not this mechanism is actually contributing significantly to the observed hydrogen intensity.
Using the centre of percussion to design a steering controller for an autonomous race car

Understanding how a race car driver controls a vehicle at its friction limits can provide insights into the development of vehicle safety systems. In this paper, a race car driver's behaviour inspires the design of an autonomous racing controller. The resulting controller uses the vehicle's centre of percussion (COP) to design feedforward and feedback steering. At the COP, the effects of rotation and translation from the rear tire force cancel each other out; consequently, the feedforward steering command is robust to the disturbances from the rear tire force. Using the COP also simplifies the equations of motion, as the vehicle's lateral motion is decoupled from the vehicle's yaw motion and highlights the challenge of controlling a vehicle when the rear tires are highly saturated. The resulting dynamics can be controlled with a linear state feedback based on a lane-keeping system with additional yaw damping. Utilising Lyapunov theory, the closed-loop system is shown to remain stable even when the rear tires are highly saturated. The experimental results demonstrate that an autonomous vehicle can operate at its limits while maintaining a minimal lateral error.
Who Bears the Balloon Risk in Commercial MBS

Much of the literature on the pricing of commercial mortgages underlying commercial mortgage-backed securities pools focuses on the effect of term default (default during the term of the loan), and ignores the possibility of balloon risk, the borrower9s inability to pay off the mortgage at maturity through refinancing or property sale. A contingent-claims mortgage pricing model that includes two default triggers—a cash flow trigger and an asset value trigger—may be used to assess the effect of balloon risk on the pricing of CMBS tranches. Simulations of cash flows for individual loans in a CMBS framework reveal how individual tranches are affected by balloon risk. Balloon risk is low at the whole-loan level, but under a number of scenarios total credit risk and balloon risk creep into investment-grade CMBS tranches and significantly impact their valuation.
Exocytic pathway-independent plasma membrane targeting of heterotrimeric G proteins

Heterotrimeric G proteins are lipid-modified, peripheral membrane proteins that function at the inner surface of the plasma membrane (PM) to relay signals from cell-surface receptors to downstream effectors. Cellular trafficking pathways that direct nascent G proteins to the PM are poorly defined. In this report, we test the proposal that G proteins utilize the classical exocytic pathway for PM targeting. PM localization of the G protein heterotrimers αsβ1γ2 and αqβ1γ2 occurred independently of treatment of cells with Brefeldin A, which disrupts the Golgi, or expression of Sar1 mutants, which prevent the formation of endoplasmic reticulum to Golgi transport vesicles. Moreover, the palmitoylation of αq was unaffected by Brefeldin A treatment, even though the palmitoylation of SNAP25 was blocked by Brefeldin A. Non-palmitoylated mutants of αs and αq failed to stably bind to βγ and displayed a dispersed cytoplasmic localization when co-expressed with βγ. These findings support a refined model of the PM trafficking pathway of G proteins, involving assembly of the heterotrimer at the endoplasmic reticulum and transport to the PM independently of the Golgi.
Membrane filter evaluations using poliovirus

Poliovirus 1, with and without radioactive label, has been used to evaluate membrane filters for several purposes in virology. Filters of several polymers will pass virus and retain larger particles. Cellulose nitrate can adsorb virus for concentration purposes. Polycarbonate does not adsorb virus and is well suited to particle sizing.
Resonance field analysis and electromagnetic coupling effects in metamaterial structures

The results of full-wave simulations of resonance responses of metamaterial structures incorporating multiple unit cells are presented. The structures under consideration include conventional metamaterials comprising arrays of split-ring resonators and cut wires, metamaterials composed of dielectric resonators, and electromagnetic shell-type cloaks consisting of either metallic or dielectric resonator arrays. The conducted studies have revealed drastic interactions between partcles in all types of metamaterials that can modify the mechanisms of wave propagation in these structures and need to be accounted for at the designing of metamaterials. The potential of utilizing integrated resonance responses to increase the tailorability of metamaterial properties is demonstrated.
A comparative analysis of contractile characteristics of the diaphragm and of respiratory system mechanics

The mean inspiratory flow rate (VT/TI) is used as an index of central respiratory 'drive', and, at rest, it varies interspecifically in proportion to body weight (BW) raised to the 0.74 power (Boggs and Tenney, 1984). VT/TI is determined by the level of central neural respiratory output, the velocity of contraction of respiratory muscles, and the mechanical characteristics of the respiratory system. We have examined the last two factors in 13 species ranging in weight from 0.025 to 515 kg. We determined the 'effective' inspiratory mechanical characteristics of the respiratory system (time constant, resistance, and compliance) and the time course of diaphragmatic contraction during bilateral supramaximal phrenic nerve stimulation in anesthetized animals. We also measured passive expiratory mechanical variables and made morphometric measurements of the diaphragm. We found that VT/TI during phrenic nerve stimulation was proportional to BW0.82. The 'effective' respiratory time constant (tau'rs) and passive expiratory time constant (tau rs) scaled in proportion to body weight with nearly similar exponents: tau'rs alpha BW0.26 and tau rs alpha BW0.21. In addition, the time constant of diaphragmatic contraction (tau mc) was proportional to BW0.20. Inspiratory time is proportional to tau'rs and tau mc, and tidal volume during stimulation was almost directly proportional to body weight. Thus, interspecific changes in VT/TI during stimulation were related to interspecific changes in the mechanical characteristics of the respiratory system and the velocity of muscular contraction. We conclude that interspecific changes in VT/TI need not reflect interspecific variation in central respiratory drive under resting conditions. We found that diaphragm weight and volume and diaphragm muscle thickness were geometrically similar in all species studied. Inspiratory pressure is an interspecific constant; therefore, by the Law of Laplace, smaller animals must develop greater tension per unit of muscle mass.
On-Site Inspection for Underground Nuclear Tests

The paper provides a brief review of the status in late 1962 of the VELA UNIFORM effort for developing and testing on-site inspection techniques. Of the techniques tested to date, it is tentatively concluded that ten had utility under the conditions existing at the GNOME event in southeastern New Mexico and at the Nevada Test Site locale of the NOUGAT-STORAX underground nuclear explosion series. Promising techniques include visual and photographic reconnaissance, changes in solid-state characteristics of certain minerals, gamma ray surveys, and after-shock monitoring. Problems still exist with respect to deeply buried explosions, polar areas, and regions of shallow water cover.
New multigrid approach for three-dimensional unstructured, adaptive grids

A new multigrid method with adaptive unstructured grids is presented. The three-dimensional Euler equations are solved on tetrahedral grids that are adaptively refined or coarsened locally. The multigrid method is employed to propagate the fine grid corrections more rapidly by redistributing the changes-in-time of the solution from the fine grid to the coarser grids to accelerate convergence. A new approach is employed that uses the parent cells of the fine grid cells in an adapted mesh to generate successively coaser levels of multigrid. This obviates the need for the generation of a sequence of independent, nonoverlapping grids as well as the relatively complicated operations that need to be performed to interpolate the solution and the residuals between the independent grids. The solver is an explicit, vertex-based, finite volume scheme that employs edge-based data structures and operations. Spatial discretization is of central-differencing type combined with a special upwind-like smoothing operators. Application cases include adaptive solutions obtained with multigrid acceleration for supersonic and subsonic flow over a bump in a channel, as well as transonic flow around the ONERA M6 wing. Two levels of multigrid resulted in reduction in the number of iterations by a factor of 5.
Aberrant Receptor Internalization and Enhanced FRS2-dependent Signaling Contribute to the Transforming Activity of the Fibroblast Growth Factor Receptor 2 IIIb C3 Isoform

Alternative splice variants of fibroblast growth factor receptor 2 (FGFR2) IIIb, designated C1, C2, and C3, possess progressive reduction in their cytoplasmic carboxyl termini (822, 788, and 769 residues, respectively), with preferential expression of the C2 and C3 isoforms in human cancers. We determined that the progressive deletion of carboxyl-terminal sequences correlated with increasing transforming potency. The highly transforming C3 variant lacks five tyrosine residues present in C1, and we determined that the loss of Tyr-770 alone enhanced FGFR2 IIIb C1 transforming activity. Because Tyr-770 may compose a putative YXXL sorting motif, we hypothesized that loss of Tyr-770 in the 770YXXL motif may cause disruption of FGFR2 IIIb C1 internalization and enhance transforming activity. Surprisingly, we found that mutation of Leu-773 but not Tyr-770 impaired receptor internalization and increased receptor stability and activation. Interestingly, concurrent mutations of Tyr-770 and Leu-773 caused 2-fold higher transforming activity than caused by the Y770F or L773A single mutations, suggesting loss of Tyr and Leu residues of the 770YXXL773 motif enhances FGFR2 IIIb transforming activity by distinct mechanisms. We also determined that loss of Tyr-770 caused persistent activation of FRS2 by enhancing FRS2 binding to FGFR2 IIIb. Furthermore, we found that FRS2 binding to FGFR2 IIIb is required for increased FRS2 tyrosine phosphorylation and enhanced transforming activity by Y770F mutation. Our data support a dual mechanism where deletion of the 770YXXL773 motif promotes FGFR2 IIIb C3 transforming activity by causing aberrant receptor recycling and stability and persistent FRS2-dependent signaling.
Russian gas and aluminium Revisiting the outlook for consumption and exports in a post-depression economy

Abstract This paper examines the export implications for natural gas and aluminium of Russia's ongoing economic transition. The rapid run-up in aluminium exports and the formation of a large capacity surplus (‘bubble’) in natural gas are seen as a direct result of the drastic shifts in the level and mix of aggregate demand, and the marked rise in the real price of these commodities. Based on a set of macroeconomic, structural and price assumptions, the paper provides a set of quantitative projections for the prospective evolution of Russian domestic demand for aluminium and gas, and draws out the potential implications for the international markets. For natural gas, the capacity hangover is seen to deflate by 2000, in tandem with the buildup of domestic consumption. In the case of aluminium, the recently experienced ‘export bubble’ is predicted to ease back gradually, and eventually disappear by 2005.
Mechanisms of corneal drug penetration. II: Ultrastructural analysis of potential pathways for drug movement.

Ultrastructure analysis was conducted in an effort to augment the results of classical kinetic studies. Scanning electron microscopy (SEM) allowed visual inspection of cellular junctions on corneal epithelium and endothelium. The addition of calcium-chelating agents to in vivo and in vitro mounted corneas demonstrated a concentration-dependent progressive expansion of the intercellular spaces of epithelium and endothelium, as seen by SEM. The expansion of these cellular junctions correlates with increases in permeability of the cornea to glycerol under similar conditions. The size of the intercellular space was estimated by transmission electron microscopy. Use of lanthanum as a marker of aqueous diffusional pathways demonstrated that the epithelial surface is not a totally occlusive barrier to transport of small hydrophilic compounds. Development of a method whereby an administered drug could be visualized in its actual pathway of movement through the cornea was undertaken, involving precipitation of specific compounds in the tissue with osmium tetroxide vapor. Results suggest that separate pathways of drug movement exist in the cornea for hydrophilic and hydrophobic compounds. Hydrophilic compounds were preferentially located in intercellular spaces, whereas hydrophobic compounds were associated with the lipid structures of the tissue. The results of these studies are consistent with a currently proposed ‘pore’ model for the penetration of drugs through the cornea.
A Molecular Modeling Based upon an X-Ray Crystal Structure: The Enzyme-Ligand Complexes between Porcine Pancreatic Elastase and Acetyl-Alanine-Alanine(Glycine)-Alanine

Molecular models of the complexes between porcine pancreatic elastase (PPE, EC 3.4.4.7), and acetyl-alanine-alanine-alanine (AAA) and acetyl-alanine-glycine-alanine (AGA) are constructed by means of molecular mechanics (MM) calculation, based upon the previously reported X-ray structure between PPE and acetyl-alanine-proline-alanine (APA). The MM calculations have been carried out in a 12 A scoop region from the alpha carbon atom of the second residue of the ligand. During the energy minimization, bond distance, bond angles, improper dihedral angles and dihedral angles are relaxed without a constrain. The resulting structures suggested that the ligands, AAA and AGA could be bound to the active site of PPE in the similar binding arrangements which had been shown in the X-ray structure between PPE and APA. The stronger inhibition of APA in vivo may be caused by the structural stability to enzymatic hydrolysis.
Broadband Cavity Ringdown Spectroscopy for Sensitive and Rapid Molecular Detection

We demonstrate highly efficient cavity ringdown spectroscopy in which a broad-bandwidth optical frequency comb is coherently coupled to a high-finesse optical cavity that acts as the sample chamber. 125,000 optical comb components, each coupled into a specific longitudinal cavity mode, undergo ringdown decays when the cavity input is shut off. Sensitive intracavity absorption information is simultaneously available across 100 nanometers in the visible and near-infrared spectral regions. Real-time, quantitative measurements were made of the trace presence, the transition strengths and linewidths, and the population redistributions due to collisions and the temperature changes for molecules such as C2H2, O2, H2O, and NH3.
Implications of the nuclear EMC effect

The discovery more than twenty years ago, by the EMC Collaboration, that the deep-inelastic-scattering DIS structure functions are influenced by the nuclear environment stunned the nuclear physics community and brought quarks and gluons into the field with great impact. A great length of time has passed, but despite a semi-infinite number of papers on the subject, there is no explanation that is universally accepted. Many models (related in one way or another to QCD) have been successful in reproducing data for deep inelastic scattering on nuclear targets, but fewer have described both the DIS and nuclear Drell-Yan experiments. Although there are some positive indications, no model has been used to predict correctly and unambiguously new independent phenomena. We review the history and discuss the best experimental prospects for future discovery.
Interfractional variations in patient setup and anatomic change assessed by daily computed tomography.

Purpose: To analyze the interfractional variations in patient setup and anatomic changes at seven anatomic sites observed in image-guided radiotherapy. Methods and Materials: A total of 152 patients treated at seven anatomic sites using a Hi-Art helical tomotherapy system were analyzed. Daily tomotherapy megavoltage computed tomography images acquired before each treatment were fused to the planning kilovoltage computed tomography images to determine the daily setup errors and organ motions and deformations. The setup errors were corrected before treatment and were used, along with the organ motions, to determine the clinical target volume/planning target volume margins. The organ motions and deformations for 3 representative patient cases (pancreas, uterus, and soft-tissue sarcoma) and for 14 kidneys of 7 patients are presented. Results: Interfractional setup errors in the skull, brain, and head and neck are significantly smaller than those in the chest, abdomen, pelvis, and extremities. These site-specific relationships are statistically significant. The margins required to account for these setup errors range from 3 to 8 mm for the seven sites. The margin to account for both setup errors and organ motions for kidney is 16 mm. Substantial interfractional anatomic changes were observed. For example, the pancreas moved up to ±20 mm and volumes of the uterus and sarcoma varied ≤30% and 100%, respectively. Conclusion: The interfractional variations in patient setup and in shapes, sizes, and positions of both targets and normal structures are site specific and may be used to determine the site-specific margins. The data presented in this work dealing with seven anatomic sites may be useful in developing adaptive radiotherapy.
Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism.

Rationale When administered chronically to rats, drugs that are effective in bipolar disorder—lithium and the anticonvulsants, valproic acid and carbamazepine—have been shown to downregulate the expression of certain enzymes involved in brain arachidonic acid (AA) release and cyclooxygenase (COX)-mediated metabolism. Phase II clinical trials with the anticonvulsant topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-d-fructopyranose sulfamate] suggest that this drug may also be effective for bipolar disorder.
The cost of graceful degradation for omission failures

An implementation of a shared object O is t-tolerant if the object remains correct and wait-free even when up to t base objects (objects used in the implementation of O) fail. The implementation is gracefully degrading if, no matter how many base objects fail, O does not fail more severely than its base objects. For the omission failure mode, we derive a lower bound on the space complexity of a gracefully degrading t-tolerant implementation. This result lets us conclude that, for omission failures, graceful degradation can be achieved only at the cost of increased space complexity.
CMV-specific immune responses and HLA phenotypes of AIDS patients who develop CMV retinitis

Summary HLA phenotype and immune responses to CMV were studied to determine whether the subset of AIDS patients who developed CMV retinitis were immunogenetically or immunologically predisposed. CMV retinitis develops in approximately 28–35% of AIDS patients and CMV encephalitis develops in 40% of those with retinitis, often leading to death. T-cell proliferation responses to CMV and HIV were assayed prospectively in individuals enrolled in a longitudinal study at the HIV Neurobehavioral Research Center (HNRC) in San Diego. Seventy-three participants, at various stages of disease, have been HLA typed and followed, clinically and immunologically, for up to 5 years. Six HIV infected individuals who eventually developed CMV retinitis, and were assayed prospectively, had a history of low T-cell proliferation to CMV antigens before they were profoundly immunosuppressed. All 10 individuals with CMV retinitis had at least one of three HLA alleles (or combinations): A2B44 ( p =0.02), B51( p =0.02), or DR7 ( p =0.01) (collective p value = 0.007). Three of the 10 had two or more of these alleles. Of AIDS patients with CD4 counts below 100 and actively at risk for retinitis, 7/15 with A2B44,51, or DR7 have developed retinitis compared to 0/13 without these HLA alleles (relative risk = 23.8). All 4 patients with these alleles who have died, had retinitis. These results suggest that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T-cell immune responses to CMV and are pre-disposed to CMV retinitis and encephalitis as immunodeficiency progresses.
Passive Elasticity of the Human Left Ventricle The "Parallel Elastic Element"

Pressure-volume (PV) and stress-strain relationships (σ-e) were utilized for evaluation of stiffness changes in the human left ventricle. A total of 45 patients were studied with data available from routine cardiac catheterization. They were divided into eight groups from which five were chosen for statistical comparison. These were the groups of normal, idiopathic hypertrophy without obstruction (IH), congestive heart failure in severe coronary artery disease (CHF-CAD1), moderate to severe CAD2, and mild to moderate CAD3. Utilizing precise pressure volume relationships, the natural elastic stiffness (dσsp./de2) for a spherical model and the stiffness constant K2 were evaluated. In addition, stress-strain relationships for ellipsoid model were utilized for evaluation of the diastolic stiffness and the stiffness constants b1 and K3 as obtained for the modified Lagrangian strain (L-L1)/L1, and the natural strain Loge(L/Lo), respectively. The constants K2, b1 and K3 were 20.3 ± 1.5, 15.0 ± 2.4 and 15.8 ± 2.3...
Bilateral intralobar pulmonary sequestration with horseshoe lung

We present an unusual case of a young woman with a several-month history of bronchopulmonary infection, symptomatic on the left side, who underwent complete studies showing bilateral pulmonary sequestration with suspected bridging tunnel. A bilateral resection was performed as a single procedure through a left thoracotomy.
Modification of the Beckman Model DU Spectrophotometer for the Measurement of Interference Filters

The source-input system of the Beckman Model DU Spectrophotometer is altered to permit the insertion of a two-inch square interference filter into a collimated beam. The over-all spectral transmission of a 1.6-inch square can be determined.
Small blood vessels and the origin of phagocytes in the rat cerebral cortex following heavy particle irradiation

Abstract Alterations in the structure of small cerebral vessels were studied with the electron microscope at various intervals following ionizing particle irradiation. The disruption of small vessels required heavier doses of irradiation than is required for destruction of neural or glial elements. The appearance of large phagocytes which might be identified with the compound granular corpuscle is dependent upon and correlated with perivascular reaction. These cells appear to be derived from the pericytes of small vessels and not from any glial element within the brain parenchyma. The appearance of dense bodies or lamellar inclusions in cytoplasm cannot constitute evidence of phagocytosis. The only cerebral element which appears to display macrophage activity seems to be derived from the vascular pericyte. It is suggested that mesodermal elements only extend beyond the basal lamina of vessels under conditions of tissue disruption. The implications of these findings with respect to the designation “microglia” is discussed.
Prospective mathematics teachers’ sense making of polynomial multiplication and factorization modeled with algebra tiles

This study is about prospective secondary mathematics teachers’ understanding and sense making of representational quantities generated by algebra tiles, the quantitative units (linear vs. areal) inherent in the nature of these quantities, and the quantitative addition and multiplication operations—referent preserving versus referent transforming compositions—acting on these quantities. Although multiplicative structures can be modeled by additive structures, they have their own characteristics inherent in their nature. I situate my analysis within a framework of unit coordination with different levels of units supported by a theory of quantitative reasoning and theorems-in-action. Data consist of videotaped qualitative interviews during which prospective mathematics teachers were asked problems on multiplication and factorization of polynomial expressions in x and y. I generated a thematic analysis by undertaking a retrospective analysis, using constant comparison methodology. There was a pattern which showed itself in all my findings. Two student–teachers constantly relied on an additive interpretation of the context, whereas three others were able to distinguish between and when to rely on an additive or a multiplicative interpretation of the context. My results indicate that the identification and coordination of the representational quantities and their units at different categories (multiplicative, additive, pseudo-multiplicative) are critical aspects of quantitative reasoning and need to be emphasized in the teaching–learning process. Moreover, representational Cartesian products-in-action at two different levels, indicators of multiplicative thinking, were available to two research participants only.
Binge Ethanol and Liver: New Molecular Developments

Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also to develop therapeutic strategies to control it. This review summarizes these recent developments.
Modeling longitudinal data on health aging and life span

Abstract We address comments from the three discussants of our paper, paying particular attention to the properties of our model likely to be of interest in new applications to complex dynamic systems.