cssi/SciSciGPT-SciSciNet huggingface dataset:
“I Believed She Could Save Me”: Rape Culture in David Foster Wallace's “Brief Interviews with Hideous Men #20”

David Foster Wallace's 1999 short story collection Brief Interviews with Hideous Men offers four homonymous stories that demonstrate a similar conceit: unnamed, silent interviewer questions one or more hideous men. The fourth and final iteration of “Brief Interviews with Hideous Men,” “B.I. #20,” is seen by many as a love story in disguise, but this article argues that that interpretation is a misreading. To view the story as a love story is to identify completely with Wallace's last hideous man. These men manipulate the women in their lives and the interviewer(s), but Wallace means for the reader to both feel implicated by their hideousness and separate enough from it to judge it. In “B.I. #20,” the nesting narratives reveal a pervasive rape culture and the ways in which its values pervert love for those who live inside it.
War Souvenir Poisoning

Sir. —We recently had an alarming case of accidental atropine sulfate poisoning in a 4-year-old boy who was brought to the emergency department after injecting himself with 2 mg of atropine from a vacuum-loaded syringe. Why was such an article within reach of a young child? The boy's uncle had recently returned home from military service. He was stationed in Saudi Arabia and issued the syringe to use as an antidote in chemical warfare, ie, in case he suffered symptoms of cholinergic poisoning. The child was observed for 24 hours after receiving two consecutive doses of activated charcoal. 1 He suffered only minor symptoms of tachycardia, mydriasis, and drying of the mucous membranes, and was released the following day. We were relieved that he had no complications, since, according to reports, people have died of anticholinergic poisoning. 2 In this case, the circumstances of the accident were more alarming
Electrophoresis on uncrosslinked polyacrylamide: Molecular sieving and its potential applications

Uncrosslinked polyacrylamide, a viscous liquid, provides a molecular sieving effect in electrophoresis qualitatively the same as that of crosslinked gels. This finding confirms previous results by others using uncrosslinked polyacrylamide mixed with various gel matrices. It provides a sieving medium constituted by an entirely and necessarily random association of inert fibers, as stipulated for interpretation of migration by the Ogston theory. Ferguson plots of several proteins in uncrosslinked polyacrylamide exhibit Yo values smaller and less divergent from one another than in 5 % crosslinked gels, suggesting a curvature of the Ferguson plots of crosslinked polyacrylamide gels at low %T. If linearity of these plots at low %T, 0 %C could be demonstrated, a means would be found to determine accurate values of free mobility by their linear extrapolation to 0 gel concentration. Potentially, uncrosslinked polyacrylamide at low concentrations may provide a tool for the analytical sieving of subcellular particles. However, electrophoresis in uncrosslinked polyacrylamide at concentrations of less than 10 % is perturbed by convection, and thus these potential applications will depend on combining it with a suitable anticonvective device.
Drug Prescribing for Elderly Patients

Objective To describe the pharmacokinetic and pharmacodynamic changes that occur with aging and to discuss common problems noted with the use of medications often prescribed for elderly patients. Design We searched the medical literature, reviewed pertinent articles, and summarized drugrelated information applicable to geriatric patients. Results Use of medications is common in the elderly population; most elderly persons take two or more different medications each day. Aging is associated with anatomic and physiologic changes that can have an effect on how medications are handled. Such changes include alterations in various volumes of drug distribution and in drug absorption, metabolism, and clearance. Elderly patients may also have increased or decreased drug effects because of alteration in receptor response. These changes in pharmacokinetics and pharmacodynamics may result in a prolonged drug half-life, an increased potential for drug toxicity, and a greater likelihood for adverse drug reactions. Conclusion Medications for elderly patients should be prescribed only after the anatomic and physiologic changes of aging are understood and with increased surveillance for potential drug toxicity or adverse drug reactions.
Nucleation of voids in irradiated metals. II. The general case

Abstract An attempt was made to calculate the co-precipitation rate of vacancies, interstitials, and gas atoms into voids, thus modelling processes occurring in the fast breeder reactor. In the co-precipitation of vacancies and interstitials, the existence of a pseudo-equilibrium distribution permitted the rate to be expressed in a form very similar to the usual nucleation equations; however, the presence of gas atoms creates severe problems. It was found that if a pseudo-equilibrium distribution is to exist, it must bear a particular functional relationship to the equilibrium distribution which obtains in the absence of excess interstitials. It is generally thought that gas atoms are present in substitutional sites; in this case the constraints are so severe that it is generally impossible to define a pseudo-equilibrium distribution. The constraints are not as severe for the less-likely case of interstitial gas atoms, but even so, the free energy of void formation must have a special functional form. A difference equation is presented that describes void nucleation in the breeder environment; we believe that a theoretical understanding of void formation in the breeder reactor will come from solution of this equation. Accordingly, we are at present attempting a numerical evaluation for the steady-state nucleation rate and incubation time.
Hepatitis C Virus NS5A Protein Modulates Transcription through a Novel Cellular Transcription Factor SRCAP

Hepatitis C virus NS5A protein transcriptionally modulates cellular genes and promotes cell growth. NS5A is likely to exert its activity in concert with cellular factor(s). Using a yeast two-hybrid screen, we have demonstrated that NS5A interacts with the C-terminal end of a newly identified cellular transcription factor, SRCAP. The authenticity of this interaction was verified by a mammalian two-hybrid assay, in vitro pull-down experiment, and an in vivo coimmunoprecipitation assay in human hepatoma (HepG2) cells. An in vitro transient transfection assay demonstrated that SRCAP can efficiently activate transcription when recruited by the Gal4 DNA-binding domain to the promoter. However, down-regulation of p21 promoter activity by NS5A was enhanced following ectopic expression of SRCAP. Together these results suggest that the interaction of NS5A and SRCAP may be one of the mechanisms by which NS5A exerts its effect on cell growth regulation contributing to hepatitis C virus-mediated pathogenesis.
The design of some new compounds to block psychotomimetic drugs.

Abstract Predictions were made from theory; (i) that N,N-diethylactamide (DAA) would not, but (ii) that N,N-diethylbutyramide (DBA) would block dimethyltryptamine (DMT) and (iii) DBA would not block mescaline or 2,5-dimethoxy-4-methyl-amphetamine (DOM). Experiments using the Bovet-Gatti profiles in rats confirmed these predictions.
Stromelysin-1 activation correlates with invasiveness in squamous cell carcinoma.

The expression of selected metalloproteinases and tissue inhibitors of metalloproteinases (TIMP) was examined in three squamous cell carcinoma (SCC) cell lines (FaDu, SiHa, A431) and a keratinocyte cell line (HaCaT) to determine which metalloproteinases function in SCC invasiveness. A Matrigel invasion assay was used to assess invasiveness of the cell lines. Only the FaDu cell line showed invasiveness in this assay, and invasion of Matrigel by FaDu cells was inhibited by treatment with the metalloproteinase inhibitor, batimastat. No correlation was found between mRNA expression for matrilysin, stromelysins 1–3, TIMP-1, or TIMP-3 and secretion of these proteins, indicating that the extracellular activity of these molecules is regulated post-transcriptionally. The SCC cell lines differed from the HaCaT line in that matrilysin and TIMP-1 proteins were detected in conditioned medium from all SCC cell lines, but not in medium from HaCaT cells. Only the invasive cell line, FaDu, released active stromelysin-1 into the culture medium. These results indicate that while matrilysin contributes to the invasive phenotype, activation of stromelysin-1 is a key regulatory step for invasiveness in SCC cells.
Low-frequency intensity noise resonance in an external cavity GaAs laser for possible laser characterization

The dependence of the (low-frequency) resonance of light intensity noise in an external-cavity GaAs laser on cavity length and bias current, combined with the dependence of the threshold current on the magnitude of the light feedback, is used to determine simultaneously the carrier recombination lifetime, the carrier injection at transparency, and the optical loss. The key to this technique is understanding the correction term to the relaxation oscillation frequency due to finite carrier density at transparency and the influence of the long external cavity transit time on the photon lifetime in the three-mirror cavity. The technique uses commercial lasers without modifying them and does not require fast electronics. >
A monoclonal antibody, MA21, recognizes a surface component that is present on F9 teratocarcinoma cells and that appears vectorially on the trophectoderm of peri-implantation-stage mouse blastocysts.

Abstract A monoclonal antibody (MAb) “MA21”, derived from lymphoid tissue of a multiparous mouse and selected for binding to mouse teratocarcinoma cell line F9, recognizes a surface antigen that appears on peri-implantation-stage mouse blastocysts. In indirect immunofluorescence assays, MAb MA21 does not bind to I-cell-through morula-stage embryos, nor to early, 3.5-day post-coitum (p.c.) blastocysts. When 3.5-day p.c. blastocysts are maintained 17 h in vitro and then assayed, MAb MA21 binds to a limited number of trophectoderm cells that are centered at the embryonic pole. As culture time lengthens, the number of antigen-expressing trophectoderm cells increases, forming a cap that spreads from the embryonic pole into the abembryonic region. Embryos maintained 48 h in vitro bind MAb MA21 over as much as 100% of the trophectoderm surface. MAb MA21 does not bind to the inner cell mass. When mouse pregnancy uteri are assayed by the immunoperoxidase method, MAb MA21 binds to extra-embryonic ectoderm and trophectoderm of 5-day p.c. implanted blastocysts, but does not bind to 6-day p.c. blastocysts. MAb MA21 recognizes a component with an estimated mol. wt of 44,000 from NP-40 detergent extracts of F9 cells and peri-implantation-stage mouse blastocysts. The component appears to be firmly associated with the plasma membrane; it is resistant to removal by high salt or moderate concentrations of non-ionic detergent.
The 'Ins' and 'Outs' of Mitochondrial Membrane Channels

Abstract The outer membrane of the mitochondrion contains thousands of copies of a pore-forming protein called VDAC or porin. Considerable progress has been made towards elucidating the molecular structure of this channel. Moreover, mounting evidence that the permeability of VDAC may be regulated is challenging the textbook notion of the outer membrane as a simple sieve. Numerous other channel activities have been detected by electrophysiological approaches in both the outer and inner mitochondrial membranes. The inner-membrane channels do not appear to be open under normal physiological conditions and so should not dissipate energy-transducing ion gradients. The biological functions of the different classes of mitochondrial channels are uncertain, but several possibilities (including protein translocation) are being explored.
Slow growth of cracks in a rate sensitive Tresca solid.

Extension of the classical theory of fracture to viscoelastic and elastic-plastic materials in which the plasticity effects are confined to a narrow band encompassing the crack front. It is suggested that the Griffith-Irwin criterion of fracture, which requires that the energy release rate computed for a given boundary value problem equal the critical threshold, ought to be replaced by a differential equation governing the slow growth of a crack prior to the onset of rapid propagation. A new term which enters the equation of motion in the dissipative media is proportional to the energy lost within the end sections of the crack, and thus it reflects the extent of inelastic behavior of a solid. A concept of 'apparent' surface energy is introduced to account for the geometry-dependent and the rate-dependent phenomena which influence toughness of an inelastic solid. Three hypotheses regarding the condition for fracture in the subcritical range of load are compared.
Effect of Rate on Changes in Conduction Velocity and Extracellular Potassium Concentration During Acute Ischemia in the In Situ Pig Heart

Rate Effects on Conduction and [K+]e During Ischemia. Introduction: The purpose nf our study was to determine if the slowing oflongitudinal intraventricular conduction in the in situ porcine heart during acute regional no-flow ischemia was rate dependent. Further, we investigated whether any rate dependence could he correlated to a rate-dependent component of the ischemiainduced rise in extracellular potassium concentration. [K+]e. Methods and Results: We studied in situ hearts in nine anesthetized open chest pigs in which acute no-flow ischemia was induced by occlusion of the left anterior descending coronary artery. To determine the effects of steady-state rate on the slowing of conduction and rise in [K+]e during ischemia, we varied the rate of stimulation during sequential occlusions from 90 to 150 beats/min. Longitudinal conduction velocity was determined by unipolar electrodes embedded in a plaque that was sutured to the epicardial surface in the center of the ischemic zone. Myocardial [K+]e was determined simultaneously by potassium-sensitive electrodes placed at or within 1 to 2 mm of the epicardium in close proximity to the activation recording electrodes. Conduction vehxity decreased more rapidly at the more rapid rates of stimulation although the reduction in conduction velocity occurring prior to the onset of conduction block was similar at both rates. The potassium change was not rate dependent and rose at the same rate regardless of the rate of stimulation. Conclusion: Our study demonstrates that the steady-state rate-dependent component of the slowing of intraventricular conduction induced by acute ischemia in the in situ porcine heart occurs in the absence of a rate-dependent component in the rise of [K+]e. Between rates of 90 and 150 beats/min, the rate dependence of the conduction slowing may be attributed to one or more potassium-independent factors such as the rate-dependent changes in resting membrane potential, in Vmax of the action potential upstroke, and in cell-to-cell uncoupling, which have hcen observed in other models of acute ischemia.
On-line NMR detection of microgram quantities of heparin-derived oligosaccharides and their structure elucidation by microcoil NMR

The isolation and purification of sufficient quantities of heparin-derived oligosaccharides for characterization by NMR is a tedious and time-consuming process. In addition, the structural complexity and microheterogeneity of heparin makes its characterization a challenging task. The improved mass-sensitivity of microcoil NMR probe technology makes this technique well suited for characterization of mass-limited heparin-derived oligosaccharides. Although microcoil probes have poorer concentration sensitivity than conventional NMR probes, this limitation can be overcome by coupling capillary isotachophoresis (cITP) with on-line microcoil NMR detection (cITP-NMR). Strategies to improve the sensitivity of on-line NMR detection through changes in probe design and in the cITP-NMR experimental protocol are discussed. These improvements in sensitivity allow acquisition of cITP-NMR survey spectra facilitating tentative identification of unknown oligosaccharides. Complete structure elucidation for microgram quantities of the purified material can be carried out through acquisition of 2D NMR spectra using a CapNMR microcoil probe.
Recombinant carcinoembryonic antigen as a reporter gene for molecular imaging

Purpose Reporter genes can provide a way of noninvasively assessing gene activity in vivo. However, current reporter gene strategies may be limited by the immunogenicity of foreign reporter proteins, endogenous expression, or unwanted biological activity. We have developed a reporter gene based on carcinoembryonic antigen (CEA), a human protein with limited normal tissue expression.
First-year engineering students' nanotechnology awareness, exposure and motivation before and after educational interventions

Educational interventions in first-year engineering programs can positively affect students' awareness of nanotechnology by introducing students to basic nanotechnology concepts and motivating them to follow nanotechnology-related career paths. The research question examined in this study is: What are the differences in exposure, awareness, and motivation between students in classrooms where a mathematical modeling activity is implemented and where a mathematical modeling activity and a simulation design project are implemented? In a pre/posttest quasi-experimental design, first-year engineering course sections were split into experimental and control groups. The experimental course sections (6 sections n=496) implemented a mathematical modeling activity and a simulation design project related to nanotechnology. The control course sections (8 sections n=703) implemented only the mathematical modeling activity. Results show that when implemented together, the simulation design project and the mathematical modeling activity are more effective than only the mathematical modeling activity in terms of increasing student awareness, exposure and motivation related to nanotechnology. Although the change in motivation is statistically significant, the effect size is low. Therefore, further research for uncovering factors linked to motivation is necessary.
Alterations in binding of inositol 1,4,5-trisphosphate to subcellular structures of rat liver during chronic endotoxemia.

Abstract Inositol 1,4,5-trisphosphate (IP 3 ) binding to, and Ca 2+ uptake and release by plasma membrane- and endoplasmic reticulum-enriched fractions of rat liver were measured after continuous Escherichia coli endotoxin (ET) administration in vivo. IP 3 binding to both fractions was significantly reduced by ET treatment. This was associated with decreased Ca 2+ uptake and impaired IP 3 -dependent Ca 2+ release. A decrease of 5′-nucleotidase specific activity of plasma membrane-enriched fraction was also observed in ET treated rats. The results suggest that previously observed impairments in the ability of hepatocytes to mobilize Ca 2+ to activate glycogen phosphorylase and to respond — when saponin permeabilized — by Ca 2+ release upon IP 3 addition during chronic endotoxemia are due to alterations in both IP 3 binding to the subcellular fractions that are imputed to be targets of IP 3 , and a decrease in the size of IP 3 -sensitive pool of releasable Ca 2+ .
5-HT is a potent relaxant in rat superior mesenteric veins

Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (~2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT1/5-HT7)>5-HT = LP-44 (5-HT7)>PNU109291 (5-HT1D) = BW723C86 (5-HT2B). 8-OH-DPAT (5-HT1A/7), CP93129 (5-HT1B), mCPBG (5-HT3/4), AS19 (5-HT7) and TCB-2 (5-HT2A) did not relax the isolated vein. Consistent with these findings, two different 5-HT7 receptor antagonists SB 269970 and LY215840 but not the 5-HT2B receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg−1 min−1, sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT7 receptor.
Analysis of intermediate product yield in distributed-feed nonisothermal tubular membrane reactors

A comparative study of yield to intermediate products obtained from the distributed-feed membrane reactor (MR) and the conventional cooled-tube plug-flow reactor (PFR) is presented. The nonisothermal, nonadiabatic one-dimensional pseudo-homogeneous reactor model was used. The analysis is presented in terms of the usual dimensionless groups (Damkohler number (Da), heat of reaction parameter, Stanton number (St), etc.) and delineates regions of parameter space where the membrane reactor gives improved yield with no higher maximum temperature. Optimal conditions for the PFR usually lie on or close to the boundaries between either pseudo-adiabatic operation (PAO) or hot-spot operation (HSO), and runaway operation. Results show that when compared under optimal operating conditions and at the same catalyst volume, reactant feed rate, temperature and pressure, the membrane reactor performance is better than that of the PFR only over restricted regions of parameter space. In general, distributed feed is preferred at higher Da, and under conditions of high heat release or lower cooling rates. The distributed-feed reactor performance can be enhanced by a mixed-feed strategy, or by slightly increased inlet temperature.
The shifting geopolitics of higher education: Inter/nationalizing elite universities in Kazakhstan, Saudi Arabia, and beyond

Abstract This article examines recent higher education projects in two resource-rich, developmental states: Kazakhstan and Saudi Arabia. These projects are indicative of broader trend across Asia to move beyond previous national universities, toward a state-initiated model of the globally competitive university, which is designed to become an regional hub for elite education. Drawing on a range of qualitative methods, I consider the geopolitical context in which these projects have been conditioned and materialized, with a focus on how they are legitimated by policy-makers in the two case countries. By reframing discussions about the globalization of higher education in terms of a geopolitics of higher education, I argue that the cases of Kazakhstan and Saudi Arabia are not exceptions set outside of the hegemonic liberal system, but that they are ‘mirrors’ of recent internationalization agendas undertaken by elite Western universities. Through considering localized discourses of promoting knowledge-based economies, I consider how elites simultaneously work with and reconfigure globally-hegemonic discourses, and specifically how these elite university projects are part of broader authoritarian political configurations in Kazakhstan and Saudi Arabia.
Muscle fatigue: MK2 signaling and myofibroblast differentiation.

In the article entitled “Lack of MK2 Inhibits Myofibroblast Formation and Exacerbates Pulmonary Fibrosis” in this issue of the AJRCMB (pp. 507–517), the authors Liu and coworkers extend their previous in vitro findings regarding the role of the kinase MK2 in myofibroblast differentiation (1). The authors present evidence that MK2−/− mice develop more severe pulmonary fibrosis in response to bleomycin, despite the fact that the mice appear to be deficient in the differentiation of myofibroblasts. The bleomycin-treated MK2−/− mice have many vimentin-positive cells in the lung, but few α–smooth muscle actin (α-SMA)–positive cells in fibroproliferative lesions. Further, MK2 loss in vivo does not result in complete loss of α-SMA expression, as α-SMA expression persists in vascular smooth muscle cells in vivo (see Liu and colleagues, Figure 4). Lungs from MK2-null mice also have more soluble collagen after bleomycin compared with wild-type mice, and their embryonic fibroblasts express increased collagen, and exhibit impaired migration in an in vitro wound assay. These are novel and important findings, particularly if the implication that lung fibrosis is pathogenically distinct from myofibroblast differentiation were found to be true in future work. Myofibroblasts were originally identified more than 30 years ago and later characterized as cells of high contractile activity, rich in the α-isoform of smooth muscle actin in stress fibers, and of high synthetic activity (matrix proteins, cytokines and chemokines, proteases/inhibitors) (2). Based on these features, and their localization at sites of active wound healing, these cells have historically been considered to be the major regulators and effectors of the matrix remodeling required for normal wound healing in many organs. Furthermore, localization of collagen-expressing myofibroblasts to areas of fibrosis in experimental pulmonary fibrosis supports the notion that myofibroblast persistence results in pathologic tissue scarring (3). In vivo cell lineage tracing and adoptive transfer approaches have shed new light on the origin and role of the myofibroblast in fibrosis in the lung and other organs.
Critical Length of the Transport-Dominated Region for Oscillating Non-Linear Reactive Processes

Abstract Beyond an instability, non-linear processes can give rise to reactive modes exhibiting sustained oscillations in particle numbers. The coupling of such an oscillatory mode to diffusional transport in a system can cause coherent spatio-temporal structures to arise and persist indefinitely, far from thermal equilibrium, provided the system is above some critical size and is maintained open to mass and energy transfer. In the case of one spatial dimension, the critical size of the system, following Goldbeter [Proc. Nat. Acad. Sci. USA 70, 3255-3259 (1973)], can be defined as that size up to which there exists exactly one unique time-independent solution (which is completely transport dominated) to the macroscopic equation that characterizes the coupling of the reactive mode to diffusional transport and which is subject to inhomogeneous boundary conditions. A theoretical estimate of the critical size is derived (valid for arbitrary systems involving multicomponent non-linear reactive processes possessing an oscillatory mode) by making use only of the parameter-dependent period of the oscillatory mode and of the elements of the diffusion tensor. This estimate specifically takes cross-diffusion into account. In the special case of simple diagonal diffusion, an illustrative comparison is made with the prediction of a more model-specific estimate of Goldbeter that involves a model for glycolytic oscillations.
Peptide folding using multiscale coarse-grained models.

The multiscale coarse-graining (MS-CG) method has been previously used to describe the equilibrium properties of peptides. The present study reveals that MS-CG models of α-helical polyalanine and the β-hairpin V5PGV5 possess the capacity to efficiently refold in simulations initiated from unfolded configurations. The MS-CG peptides exhibit free energy landscapes that are funneled toward folded configurations and two-state folding behavior, consistent with the known characteristics of small, rapidly folding peptides. Moreover, the models demonstrate enhanced sampling capabilities when compared to systems with full atomic detail. The significance of these observations with respect to the theoretical basis of the MS-CG approach is discussed. The MS-CG peptides were used to reconstruct atomically detailed configurations in order to evaluate the extent to which MS-CG ensembles embody all-atom peptide free energy landscapes. Ensembles obtained from these reconstructed configurations display good agreement with ...
A parallel domain decomposition BEM for diffusion problems with surface reactions

Abstract A parallel domain decomposition boundary element method (BEM) is developed for the solution of three-dimensional multispecies diffusion problems. The chemical species are uncoupled in the interior of the domain but couple at the boundary through a nonlinear surface reaction equation. The method of lines is used whereby time is discretized using the finite difference method and space is discretized using the boundary element method. The original problem is transformed into a sequence of nonhomogeneous modified Helmholtz equations. A Schwarz Neumann–Neumann iteration scheme is used to satisfy interfacial boundary conditions between subdomains. A segregated solver based on a quasi-predictor–corrector time integrator is used to satisfy the nonlinear boundary conditions on the reactive surfaces. The accuracy and parallel efficiency of the method is demonstrated through a benchmark problem.
Distal to proximal development of peripheral nerves requires the expression of neurofilament heavy

At the initiation of radial growth, neurofilaments are likely to consist primarily of neurofilament light and medium as neurofilament heavy expression is developmentally delayed. To better understand the role of neurofilament heavy in structuring axons, axonal diameter and neurofilament organization were measured in proximal and distal segments of the sciatic nerve and along the entire length of the phrenic nerve. Deletion of neurofilament heavy reduced axonal diameters and neurofilament number in proximal nerve segments. However, neurofilament spacing was greater in proximal versus distal phrenic nerve segments. Taken together, these results suggest that loss of neurofilament heavy reduces radial growth in proximal axonal segments by reducing the accumulation of neurofilaments. As neurofilament heavy expression is developmentally delayed, these results suggest that without neurofilament heavy, the neurofilament network is established in a distal to proximal gradient perhaps to allow distal axonal segments to develop prior to proximal segments.
The triphasic amphetamine lethal dose curve in mice and its possible relationship to drug metabolism

Abstract The possible relationship between metabolism and the triphasic lethal dose curve of d -amphetamine in mice was investigated. Inhibition of hepatic oxidative metabolism with SKF 525-A (diethylaminoethyl 2,2-diphenylvalerate:HCl), Lilly 18947 (2,4-dichloro-6-phenyl-phenoxyethyldiethylamine·HBr), or piperonyl butoxide abolished the triphasic response in mortality that is usually obtained for the lethal dose curve of d -amphetamine in mice. CNS properties of these agents were not responsible for this change. Although inhibitory amphetamine metabolic-intermediate (MI) complexes were formed in mouse microsmes in vitro , only very small amounts of amphetamine MI complexes were found in vivo . It was concluded that amphetamine MI complexes did not affect amphetamine metabolism and were not involved in the mechanisms whereby changes in metabolism affect mortality.
Abstract P6-11-12: A Novel Capecitabine Schedule (7 on — 7 off) Is Feasible with Lapatinib for Patients with HER2-Positive Metastatic Breast Cancer Refractory to Trastuzumab

Background Capecitabine (C) administered for 14 days followed by a 7 day rest (14—7) in combination with lapatinib (L) improved TTP in patients (pts) with HER2(+) metastatic breast cancer (MBC) that progressed following trastuzumab (T). Our mathematical modeling of C dosing predicted 7 days of therapy followed by 7 days of rest (7—7) to maximize efficacy and minimize drug-related toxicity. In xenograph models, C (7—7) was better tolerated than C (14—7) at higher doses and led to improved survival. We established the maximum tolerated dose of C (7—7) to be 2,000 mg twice daily and have studied C (7—7) in combination with targeted therapies. We now report the results of C (7—7) with L in pts with trastuzumab-refractory HER2(+) MBC. Methods Eligible pts had measurable, HER2(+) MBC with progression following T. HER2(+) is defined as 3+ on IHC or FISH-amplified. Pts had normal LVEF by MUGA, ECOG performance status (PS) ≥2, and 6 months, and progression free survival (PFS). Using a Simon optimal 2-stage design, with alpha 10% and power 90% to discriminate between RR 10% and 25%, 21 pts were planned for the 1st stage. If >2 pts responded, then 29 additional pts were to have been enrolled to 2nd stage. If >7/50 pts responded, C (7—7) with L would be considered worthy of further study. Results As of 6/14/10, 22 pts were enrolled on study with the following characteristics: median (med) age 55 years (42-72), med PS 0 (0-2), ER/PR(+) 12, HER2(+) 22, med LVEF 64% (51-70%). Sites of MBC include viscera 16, brain 3. Prior therapy includes 8 pts with adjuvant anthracycline and taxane exposure, 4 pts with adjuvant T, 18 pts with metastatic T, and a med of 1 CRx for MBC. After a med of 5 cycles (1-16), 18 patients are evaluable for response: 0 CR, 3 PR, 6 SD >6 months, 9 SD 10% of patients include: hand-foot syndrome (gr 3: 5%, gr2: 41%), diarrhea (gr 3: 0%, gr 2: 23%), elevated AST/ALT or bilirubin (gr 3: 0%, gr 2: 18%). There have been no declines in LVEF. Conclusion Due to slower than expected accrual and an anticipated randomized, phase III trial comparing C (7—7) with C (14—7), we closed this study to further accrual. However, our data suggests that C (7—7) with lapatinib is active, well-tolerated, feasible and associated with mild gastrointestinal toxicity in pts with trastuzumab-refractory, HER2(+) MBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-12.
Hydrodechlorination of chlorofluorocarbons CF3-CFCl2 and CF3-CCl3 over Pd/carbon and Pd black catalysts

Abstract The reaction of hydrodechlorination for the chlorofluorocarbons (CFCs) CF 3 –CFCl 2 and CF 3 –CCl 3 was studied over Pd supported on carbon and Pd black catalysts. The rates and selectivity were similar on all samples although Pd black samples had a higher selectivity for the more hydrogenated products. The difference in selectivity and rate for Pd black is attributed to the presence of an impurity on the surface. The reaction orders are about first order in CFC, half-order in H 2 , and inverse first-order in HCl. These results indicate that the irreversible adsorption of CFC is the rate-determining step and that H 2 and HCl are equilibrated with hydrogen and chlorine on the surface. Experiments with D 2 on CF 3 –CFHCl confirm that the adsorption step is irreversible.
Cost and effectiveness of physician peer review in reducing medicare overutilization

Abstract There has been concern that some physicians within the U.S. Medicare program may be rendering medical attention unecessarily. To help curb this possible overutilization, peer review committees have been formed in certain areas. These committees of practicing physicians examine utilization practices of doctors. The objective of this study is to determine the cost and effectiveness of the peer review process. In order to do this, we compare the costs and benefits resulting from peer review. The benefits are two types. One type is recoverable overpayments, which peer review has established as amounts that were paid for unnecessary medical attention. The other type is the deterrent to physicians against overutilization, due to the presence of peer review. The findings of this study are that each of the benefits of peer review substantially outweigh its costs, and that the benefits due to the deterrent effect of peer review are evident in all review areas considered.
Renal response to metabolic acidosis: Role of mRNA stabilization

The renal response to metabolic acidosis is mediated, in part, by increased expression of the genes encoding key enzymes of glutamine catabolism and various ion transporters that contribute to the increased synthesis and excretion of ammonium ions and the net production and release of bicarbonate ions. The resulting adaptations facilitate the excretion of acid and partially restore systemic acid–base balance. Much of this response may be mediated by selective stabilization of the mRNAs that encode the responsive proteins. For example, the glutaminase mRNA contains a direct repeat of 8-nt AU sequences that function as a pH-response element (pHRE). This element is both necessary and sufficient to impart a pH-responsive stabilization to chimeric mRNAs. The pHRE also binds multiple RNA-binding proteins, including ζ-crystallin (ζ-cryst), AU-factor 1 (AUF1), and HuR. The onset of acidosis initiates an endoplasmic reticulum (ER)-stress response that leads to the formation of cytoplasmic stress granules. ζ-cryst is transiently recruited to the stress granules, and concurrently, HuR is translocated from the nucleus to the cytoplasm. On the basis of the cumulative data, a mechanism for the stabilization of selective mRNAs is proposed. This hypothesis suggests multiple experiments that should define better how cells in the kidney sense very slight changes in intracellular pH and mediate this essential adaptive response.
Lean-NOx reduction catalysis by metal-complex impregnated molecular sieves – Effect of ligands and metals

Abstract We have developed lean-NOx catalysts using modified mesoporous molecular sieves which operate under very low hydrocarbon concentrations. Transition metal (copper and iron)-complex impregnated mesoporous molecular sieves have been synthesized. Cryptand type ligands (L1 and L2) have been used for complex formation. The ligand plays a crucial role in the complex formation and catalytic activity. These metal-complex impregnated molecular sieves are further treated with [Pd(NH3)4] Cl2. Fe–L2 and Cu–L2-based catalysts are active towards NOx reduction under oxygen rich (lean-NOx) conditions. The catalytic activity towards NOx, CO and HC was studied using simulated exhaust gas, as well as engine exhaust gas from a lean burning gasoline engine. Using engine exhaust gas at an air/fuel ratio of 16.10, test results showed a reduction of NOx up to 10% at inlet temperatures ranging from 260°C to 285°C and HC/NOx=2/1.
Gene delivery and expression in human retinal pigment epithelial cells: effects of synthetic carriers, serum, extracellular matrix and viral promoters

Non-viral gene therapy is a potential treatment to many incurable retinal diseases. To fulfill this promise, plasmid DNA must be delivered to the retinal target cells. We evaluated the efficacy of synthetic DNA complexing compounds in transfecting primary human retinal pigment epithelial (RPE) cells in vitro. Fetal human RPE cells were cultured with or without extracellular matrix (ECM), produced using calf corneal endothelial cells. Plasmids encoding nuclear localizing beta galactosidase or luciferase (pRSVLuc, pCLuc4, pSV2Luc) were complexed in water at various +/- charge ratios using cationic lipids (Lipofectin, DOTAP, DOGS), polyethylene imines (25 and 750 kDa), and with degraded 6th generation starburst polyamidoamine dendrimers. Luciferase was quantified using a luminometric assay and beta galactosidase with X-gal staining. Toxicities of transfections were evaluated with the MTT-assay. Using beta galactosidase as the reporter gene naked DNA did not transfect RPE cells at measurable levels whereas 1-5% of the cells expressed histochemically detectable amounts of the gene after transfection with cationic lipid DNA complexes. In RPE cells, Rous sarcoma virus and cytomegalovirus (CMV) were more efficient promoters than SV40 in driving luciferase expression, and CMV was chosen for further experiments. At optimal complex charge ratios, expression levels of luciferase were > 10(9) light units/mg protein after transfection using dendrimers and PEI25, while transfection mediated with the other carriers resulted in luciferase expression levels of 10(7)-10(9) light units/mg protein or less. In general, dendrimers and large molecular weight PEI were less toxic than cationic lipids or PEI25 to RPE cells. Serum and ECM decreased gene expression to the RPE cells with all carriers. Despite low percentage of transfected cells the transgene expression per RPE cell is high, important feature in the retinal tissue with small dimensions, in particular in the case of secreted gene products. Degraded dendrimers and high molecular weight PEI exhibited the best combination of high activity and low toxicity in RPE cell transfection.
Accurate Boussinesq oceanic modeling with a practical, ''Stiffened'' Equation of State

Abstract The Equation of State of seawater (EOS) relates in situ density to temperature, salinity and pressure. Most of the effort in the EOS-related literature is to ensure an accurate fit of density measurements under the conditions of different temperature, salinity, and pressure. In situ density is not of interest by itself in oceanic models, but rather plays the role of an intermediate variable linking temperature and salinity fields with the pressure-gradient force in the momentum equations, as well as providing various stability functions needed for parameterization of mixing processes. This shifts the role of EOS away from representation of in situ density toward accurate translation of temperature and salinity gradients into adiabatic derivatives of density. In this study we propose and assess the accuracy of a simplified, computationally-efficient algorithm for EOS suitable for a free-surface, Boussinesq-approximation model. This EOS is optimized to address all the needs of the model: notably, computation of pressure gradient – it is compatible with the monotonized interpolation of density needed for the pressure gradient scheme in sigma-coordinates of Shchepetkin and McWilliams (2003) , while more accurately representing the pressure dependency of the thermal expansion and saline contraction coefficients as well as the stability of stratification; it facilitates mixing parameterizations for both vertical and lateral (along neutral surfaces) mixing; and it leads to a simpler, more robust, numerically stable barotropic–baroclinic mode splitting without the need of excessive temporal filtering of fast mode. In doing so we also explore the implications of EOS compressibility for mode splitting in non-Boussinesq free-surface models with the intent to design a comparatively accurate algorithm applicable there.
A Parameterization for the Effects of Ozone on the Wave Driving Exerted by Equatorial Waves in the Stratosphere

An equatorial b-plane model of the tropical stratosphere is used to examine the effects of ozone on Kelvin, Rossby‐gravity, equatorial Rossby, inertia‐gravity, and smaller-scale gravity waves. The model is composed of coupled equations for wind, temperature, and ozone volume mixing ratio, which are linearized about a zonally averaged background state. Using the Wentzel‐Kramers‐Brillouin (WKB) formalism, equations are obtained for the vertical spatial scale, spatial damping rate, and amplitude of the waves. These equations yield an analytical expression for the ozone-modified wave driving of the zonal-mean circulation. The expressionforthewavedrivingprovidesanefficientparameterizationthatcan beimplemented intomodels that are unable to spontaneously generate the ozone-modified, convectively coupled waves that drive the quasibiennial and semiannual oscillations of the tropical stratosphere. The effects of ozone on the wave driving, which are strongly modulated by the Doppler-shifted frequency, are maximized in the upper stratosphere, where ozone photochemistry and vertical ozone advection combine to augment Newtonian cooling. The ozone causes a contraction in spatial scale and an increase in the spatial damping rate. In the midstratosphere to lower mesosphere, the ozone-induced increase in wave driving is about 10%‐30% for all wave types, but it can be as large as about 80% over narrow altitude regions and for specific wave types. In the dynamically controlled lower stratosphere, vertical ozone advection dominates overmeridionalozoneadvectionand opposesNewtoniancooling,causing,on average,a10%‐15%reduction in the damping rate.
The role of in situ reforming in plasma enhanced ultra lean premixed methane/air flames

This paper describes a mechanism for the stabilization of ultra lean premixed methane/air flames by pulsed nonequilibrium plasma enhancement. It is shown that the pulsed discharge plasma produces a cool ({proportional_to}500-600 K) stream of relatively stable intermediate species including hydrogen (H{sub 2}) and carbon monoxide (CO), which play a central role in enhancing flame stability. This stream is readily visualized by ultraviolet emission from electronically excited hydroxyl (OH) radicals. The rotational and vibrational temperature of this ''preflame'' are determined from its emission spectrum. Qualitative imaging of the overall flame structure is obtained by planar laser-induced fluorescence measurements of OH. Preflame nitric oxide (NO) concentrations are determined by gas sampling chromatography. A simple numerical model of this plasma enhanced premixed flame is proposed that includes the generation of the preflame through plasma activation, and predicts the formation of a dual flame structure that arises when the preflame serves to pilot the combustion of the surrounding non-activated premixed flow. The calculation represents the plasma through its ability to produce an initial radical yield, which serves as a boundary condition for conventional flame simulations. The simulations also capture the presence of the preflame and the dual flame structure, and predict preflame levels ofmore » NO comparable to those measured. A subsequent pseudo-sensitivity analysis of the preflame shows that flame stability is most sensitive to the concentrations of H{sub 2} and CO in the preflame. As a consequence of the role of H{sub 2} and CO in enhancing the flame stability, the blowout limit extensions of methane/air and hydrogen/air mixtures in the absence/presence of a discharge are investigated experimentally. For methane/air mixtures, the blowout limit of the current burner is extended by {proportional_to}10% in the presence of a discharge while comparable studies carried out in lean hydrogen/air flames fail to extend this limit. (author)« less
Virtual-real interference in a dense potassium vapor

We investigate the interference between virtual and real population amplitudes in a dense potassium vapor using transient four-wave mixing with shaped pulses. Results for the D/sub 1/ line agree with theory, but D/sub 2/ results behave anomalously.
Barrier Function of Intestinal Epithelial Tight Junctions (TJ)

Intestinal epithelial tight junctions are the rate limiting barriers to passive transepithelial movement of hydrophilic solutes. We have studied these important barriers in Ussing chambers using isolated sheets of mammalian intestinal epithelia and monolayers of the T84 human intestinal epithelial cell line. Studies have included both electrophysiologic and morphologic techniques. These studies show tight junctions to be highly dynamic structures which may be influenced pharmacologically or by physiologic challenges. Additionally, elements of inflammatory responses, such as the presence of the cytokine gamma-interferon, or the transepithelial migration by polymorphonuclear leukocytes, lead to deterioration in TJ barrier function. Such events may contribute to the epithelial barrier defects seen in patients with IBD.