cssi/SciSciGPT-SciSciNet huggingface dataset:
Cloning and expression of Xenopus Prickle, an orthologue of a Drosophila planar cell polarity gene

We have cloned Xenopus orthologues of the Drosophila planar cell polarity (PCP) gene Prickle. Xenopus Prickle (XPk) is expressed in tissues at the dorsal midline during gastrulation and early neurulation. XPk is later expressed in a segmental pattern in the presomitic mesoderm and then in recently formed somites. XPk is also expressed in the tailbud, pronephric duct, retina, and the otic vesicle. The complex expression pattern of XPk suggests that PCP signaling is used in a diverse array of developmental processes in vertebrate embryos.
The genetic basis of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive elevation of pulmonary artery pressure, pulmonary vascular resistance, right ventricular failure, and a high mortality rate. The etiology of PAH is heterogeneous and incompletely understood. Based on clinical classification, WHO Group 1 PAH includes sporadic disease (idiopathic PAH), inherited PAH (heritable PAH), and association with certain medical conditions (associated PAH). Genes play an important role in idiopathic and heritable PAH. Mutations in bone morphogenetic protein receptor 2 (BMPR2), a member of the transforming growth factor β (TGFβ) superfamily of receptors, have been identified in 70 % of cases of familial PAH, as well as in 10–40 % of cases of idiopathic PAH. Mutations in ALK-1, ENG, SMAD4 and SMAD8, other TGFβ family members, are additional rare causes of PAH. CAV1 regulates SMAD2/3 phosphorylation, and mutations in CAV1 are a rare cause of PAH. KCNK3 is a member of the two-pore domain potassium channels expressed in pulmonary artery smooth muscle cells, and mutations in KCNK3 are a rare cause of both familial and IPAH. The genetics of PAH are complex due to incomplete penetrance and genetic heterogeneity. In addition to rare mutations as a monogenic cause of HPAH, common variants in cerebellin 2 (CBLN2) increase the risk of PAH by approximately twofold. PAH in children is much more heterogeneous than in adults and can be associated with several genetic syndromes, specifically syndromes with congenital heart disease, vascular disease, and hepatic disease. Clinical genetic testing is available for PAH and should be considered in families to allow for more definitive risk stratification and allow for reproductive planning.
Cultured Human Epidermal Cells Do Not Synthesize HLA-DR

All nucleated cells express HLA-A, B, and C antigens. However, only a few cells, including epidermal cells, demonstrate HLA-DR antigens which are potent transplantation immunogens in man. The current study was undertaken to determine if epidermal cells continue to synthesize and/or express HLA-DR antigens after prolonged in vitro culture. Epidermal cells cultured for 7days or more no longer stimulated allogeneic lymphocytes in the epidermal cell-lymphocyte reaction. Indirect immunofluorescence light microscopy of cultured cells using mouse monoclonal antibody to HLA-DR antigen confirmed that these cells do not express HLA-DR antigens whereas they retain β 2 -microglobulin. Detergent extracts of 12-day cultured epidermal cells biosynthetically labeled with 35 S-methionine were immunoprecipitated with monoclonal anti-DR antibody and analyzed by the method of two-dimensional polyacrylamide gel electrophoresis. No radiolabeled proteins were found on these gels in the regions where HLA-DR molecules are known to migrate. These data indicate that HLA-DR antigen is absent from cultured epidermal cells. Finally, we describe a technique for growing epidermal cells on a gelatin membrane which allows subsequent removal of intact cell monolayers from the culture dish. Such monolayers may be useful for purposes of transplantation.
Novel Pyrrolopyrimidine-Based α-Helix Mimetics: Cell-Permeable Inhibitors of Protein-Protein Interactions

There is considerable interest in developing non-peptidic, small-molecule α-helix mimetics to disrupt α-helix-mediated protein−protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such α-helix mimetics with increased conformational rigidity. We also developed a facile solid-phase synthetic route that is amenable to divergent synthesis of a large library. Using a fluorescence polarization-based assay, we identified cell-permeable, dual MDMX/MDM2 inhibitors, demonstrating that the designed molecules can act as α-helix mimetics.
SYNTHESIS AND CHARACTERIZATION OF A NOVEL SPIN-LABELED AFFINITY PROBE OF HUMAN ERYTHROCYTE BAND 3 : CHARACTERISTICS OF THE STILBENEDISULFONATE BINDING SITE

A new spin-labeled maleimide derivative of the anion exchange inhibitor 4-4'-diaminodihydrostilbene-2,2'-disulfonate (H2DADS) has been synthesized as a site-specific molecular probe of the stilbenedisulfonate binding site of the anion exchange protein 1 (AE-1; band 3) in human erythrocytes. This probe, SL-H2DADS-maleimide, specifically and covalently labels the Mr 17 kDa integral membrane segment of band 3 with a 1:1 stoichiometry and inhibits essentially 100% of the band 3-mediated anion exchange. The linear V1 EPR spectrum of spin-labeled intact erythrocytes is indicative of a spatially isolated probe which is effectively immobilized on the submicrosecond time scale. Several independent lines of experimental evidence have shown that the nitroxide moiety of SL-H2DADS-maleimide-labeled band 3 is sequestered in a highly protected protein environment. These results are consistent with the observation that the spin-label is rigidly linked to band 3 in a fixed orientation with respect to the membrane normal axis [Hustedt, E. J., & Beth, A. H., (1996) Biochemistry 35, 6944-6954]. The nitroxide moieties of the SL-H2DADS-maleimide-labeled band 3 dimer are greater than 20 A from each other and are also more than 20 A from a monomer-monomer contact surface defined by cross-linking with the spin-labeled reagent BSSDA [bis(sulfo-N-succinimidyl)doxyl-2-spiro-5'-azelate]. These properties make SL-H2DADS-maleimide an extremely useful molecular probe for characterization of the physical properties of the band 3 stilbenedisulfonate binding site, determination of distances between the stilbenedisulfonate site and other segments of band 3, and investigation of the global rotational dynamics of human erythrocyte band 3.
Dual-color flow cytometric analysis of phenotype, activation marker expression, and proliferation of mitogen-stimulated bovine lymphocyte subsets

Abstract Bovine peripheral blood mononuclear cells were cultured in vitro for 3 days with the mitogens concanavalin A (Con A), pokeweed mitogen (PWM), phytohemagglutinin (PHA), and anti-CD3 monoclonal antibody. Activation of T-lymphocyte subsets (CD4 + , CD8 + , and γδ T-cell receptor + ) and of B-cells was measured by two-color flow cytometric analysis of subset expression of IL-2 receptor alpha (CD25) and MHC class II. Proliferation of lymphocyte subsets was directly measured by two-color flow cytometric analysis of fluorescence intensity of PKH2, a fluorescent dye that stably incorporates into cell membranes. CD4 + and CD8 + T-cell subsets were stimulated by all the mitogens to increase expression of IL2r and MHC II and to proliferate. δγ + T-cells responded to all four mitogens with increased IL2r and MHC II expression. Con A and PHA caused measurable proliferation of γδ + T-cells, but PWM and anti-CD3 did not. B-cells generally responded to the mitogens with increased IL2r and MHC II expression. B-cells proliferated when incubated with Con A, but did not measurably proliferate in response to PWM, PHA, or anti-CD3.
Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages

HIV-1 infection requires fusion of viral and cellular membranes in a reaction catalyzed by the viral envelope proteins gp120 and gp41. We recently reported that efficient HIV-1 particle fusion with target cells is linked to maturation of the viral core by an activity of the gp41 cytoplasmic domain. Here, we show that maturation enhances the fusion of a variety of recombinant viruses bearing primary and laboratory-adapted Env proteins with primary human CD4+ T cells. Overall, HIV-1 fusion was more dependent on maturation for viruses bearing X4-tropic envelope proteins than for R5-tropic viruses. Fusion of HIV-1 with monocyte-derived macrophages was also dependent on particle maturation. We conclude that the ability to couple fusion to particle maturation is a common feature of HIV-1 Env proteins and may play an important role during HIV-1 replication in vivo.
The simulation of Coulomb friction in mechanical systems

Coulomb or dry friction occurs in mechanical systems when nonlubricated surfaces come into sliding contact. The force resulting from Coulomb friction has a magnitude dependent on the contact force and a direc tion opposite to the relative velocity. If the re lative velocity is zero, the Coulomb friction assumes the value, within bounds, to maintain zero velocity. This, of course, presents the opportunity for a variety of equilibrium configurations.This paper presents an overview of the common tech niques for the digital simulation of Coulomb fric tion. All these techniques use the relative velocity to determine the friction force and are therefore flawed since they cannot predict multiple equilibrium positions. By means of an example, this paper shows that modeling Coulomb friction as a function of posi tion rather than of velocity allows multiple equili bria and offers features that are useful in modeling high-friction, low-mass systems.
The Texture of the Universeaa

Just as the texture of an antique fabric is the result of the vanished loom that made it, the present texture of the universe is a result of physical processes operating in a distant and inaccessible epoch. An adequate justification for detailed study of the threedimensional distribution of galaxies would be to derive an accurate description of the ways galaxies cluster. Yet the value of this work is greatly enriched by the prospect that studies of today's galaxies may reveal important properties of conditions arising from a hot big bang. No one doubts (except Ostriker and Cowie)16 that the principal mechanism for forming galaxies and galaxy clusters is gravitational instability. Evolution from very large structures (lo" M,) down to galaxy sizes is favored in the picture advocated by Zeldovich and his collaborators,20 while the assembly of large structures from smaller ones characterizes the clustering picture described by Peebles." Looking for structure, both density enhancements and voids in the galaxy distribution, on large scales (of order 50 h ~ Mpc), may provide important clues on the fossilized structure derived from primeval galaxy evolution. One approach to studying the large-scale structure is to examine in detail the largest nearby structure: the local supercluster. Assembling the nearby structure requires accurate distance measures to individual galaxies. During the past decades, this work has been carried forward by de V a u c o ~ l e u r s ~ * ~ and has recently been
Complications of colostomy.

In a series of 307 colostomies established in 296 patients, there were complications in 53 patients (16 per cent), of whom 41 had reoperations to correct the complications. One patient died of sepsis following operation for a perforation caused by an irrigating catheter.
Effects of manipulating progesterone and NMDA receptors in the ventral tegmental area for lordosis of hamsters and rats

Progesterone (P4) has actions in the ventral tegmental area (VTA) to regulate female sexual behavior in rodents. However, there are few intracellular progestin receptors (PRs) that have been identified in the VTA through which P4 may have its actions to facilitate lordosis. There are N-methyl-d-aspartate receptors (NMDARs) in the VTA that may be a substrate for P4’s effects. We investigated the effects of pharmacologically manipulating NMDARs in the VTA for E2- and P4-facilitated lordosis of hamsters and rats. We examined the effect of systemic injections (intraperitoneal; IP) and bilateral infusions to the VTA of the highly specific, competitive NMDAR antagonist, 9-0-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959); 0, 0.3, and 1 mg/kg IP and 0, 1.0, and 10 ng/μl intra-VTA), on lordosis of estradiol-primed (E2; 10 μg) and P4-primed (0, 50, 250, or 500 μg) ovariectomized hamsters and rats. Intra-VTA administration of the NMDAR antagonist, LY235959, produced similar effects as systemic administration to enhance lordosis, particularly in E2-primed rats or hamsters administered moderate P4 levels (less than 500 μg). Administration of LY235959 to the substantia nigra did not produce similar effects as intra-VTA infusions for lordosis. Together, these data suggest that blocking NMDARs in the VTA enhances lordosis of hamsters and rats.
A Brief History of the Gordon Research Conference in Chemistry Education Research and Practice

This article presents a brief history of the Gordon Research Conference: Chemistry Education Research and Practice, highlights the benefits of attending such a conference, and describes the application procedure for the 2011 conference.
Sleep Problems and PTSD Symptoms Interact to Predict Marijuana Use Coping Motives: A Preliminary Investigation

The present study empirically tested the theory-based hypothesis that greater sleep problems and post-traumatic stress disorder (PTSD) symptom severity would both individually and multiplicatively predict higher levels of coping-motivated marijuana use. Twenty (15 women) adults (M age = 34.00 years, SD = 11.96) who had PTSD and were currently using marijuana participated. Results indicated a positive independent relation with sleep problems and a significant interaction between sleep problems and PTSD symptom severity in relation to coping-motivated marijuana use. Results also indicated nonsignificant omnibus regression models for all other marijuana use motives. The results suggest that there may be segments of the PTSD population that are more likely to use marijuana to cope by virtue of individual differences in sleep problems.
San Patrignano: A Narrative Approach to Substance Abuse Treatment

In June 2013, a group of graduate social work students from New York University embarked on a course of study on International Perspectives on Substance Use Problems.11 The course was offered as a ...
Tractable Chemical Models for CVD of Silicon and Carbon

Tractable chemical models are validated for the CVD of silicon and carbon. Dilute silane (SiH4) and methane (CH4) in hydrogen are chosen as gaseous precursors. The chemical mechanism for each systems Si and C is deliberately reduced to three reactions in the models: one in the gas phase and two at the surface. The axial-flow CVD reactor utilized in this study has well-characterized flow and thermal fields and provides variable deposition rates in the axial direction. Comparisons between the experimental and calculated deposition rates are made at different pressures and temperatures.
The Many Forms and Functions of Long Term Plasticity at GABAergic Synapses

On February 12th 1973, Bliss and Lomo submitted their findings on activity-dependent plasticity of glutamatergic synapses. After this groundbreaking discovery, long-term potentiation (LTP) and depression (LTD) gained center stage in the study of learning, memory, and experience-dependent refinement of neural circuits. While LTP and LTD are extensively studied and their relevance to brain function is widely accepted, new experimental and theoretical work recently demonstrates that brain development and function relies on additional forms of plasticity, some of which occur at nonglutamatergic synapses. The strength of GABAergic synapses is modulated by activity, and new functions for inhibitory synaptic plasticity are emerging. Together with excitatory neurons, inhibitory neurons shape the excitability and dynamic range of neural circuits. Thus, the understanding of inhibitory synaptic plasticity is crucial to fully comprehend the physiology of brain circuits. Here, I will review recent findings about plasticity at GABAergic synapses and discuss how it may contribute to circuit function.
Association of increased interferon- inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus

Objective To study 5 type I interferon (IFN)–inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations. Methods Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite. Results Each gene was highly expressed in SLE patients compared with normal controls (P ≤ 0.0003) or disease controls (P ≤ 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti–double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009). Conclusion The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.
A Computer-Generated Content Analysis of Issues Identified by Elementary Education Preservice Teachers:

Reported are the results of a computer-generated content-analysis procedure with open-ended methodology to identify issues of importance to elementary-education preservice teachers. Based on the fi...
The use of a circulating fluidized bed absorber for the control of sulfur dioxide emissions by calcium oxide sorbent via in situ hydration

Received 20 August 1994; revised 27 February 1995 Abstract A circulating fluidized bed absorber (CFBA) was developed and evaluated for sulfur dioxide removal from flue gas by use of CaO sorbent at humid conditions. SO2 removal in this process strongly depends on the system approach to saturation temperature, which increases with an increase of the approach to saturation temperature (smaller A T). The operability of the CFBA by use of very large CaO particles (initial size > 1800/zm) indicates substantial cost savings for application to full scale systems. A CFBA reactor model based on the assumption of a turbulent fluidization region, was developed for system analysis and SO2 removal data analysis. The model coupled a particle population model for calculation of the bed particle size distribution, and the shrinking core model for the chemical reaction. The particle size distribution calculated by the particle population model showed a reasonable trend for the size reduction. The reaction rate constant, ks, was found to be a function of the system approach to saturation temperature; the value of ks increases exponentially with an increase of the approach to saturation temperature. This model, with some modifications could be successfully used in the prediction of SO2 removal efficiency with knowledge of operating variables in the CFBA process, such as the sorbent feed rate, particle elutfiation rate, solids recycle rate, and the bed weight at steady-state operation.
The interaction of irradiation and adriamycin in intestinal crypt cells.

Abstract The intestinal crypt cell assay was used to evaluate Adriamycin (ADR) and radiation injury in LAF 1 mice. The MTD (LD 01 / 60 ) for ADR was 8 mg/kg. Crypt cell survival was reduced to 30% of the level of survival after radiation alone when drug was given at the MTD 2 hr before or 3 hr after irradiation. Determination of crypt cell survival from −48 to +48 hr relative to 1210 rad showed little fluctuation and no evidence of a time interval yielding enhanced response. When a radiation survival curve was measured 2 hr after a dose of 8 mg/kg, it paralleled the control curve with a shift toward lower radiation doses reflecting a 70% cell kill by drug. The 3 hr split dose survival ratio of 4–6 was similar to the control values in two separate experiments. ADR appears to be toxic to intestinal crypt cells, but does not inhibit repair of radiation injury.
Toward the Syntheses of Universal Ligands for Metal Oxide Surfaces: Controlling Surface Functionality through Click Chemistry

A new means for functionalizing metal oxide surfaces, specifically nanoparticles, is demostrated. This process involves the design of stable ligands that bind strongly to the surface of metal oxides and can undergo further chemical modification via click chemistry, with both small molecules as well as polymers, to yield metal oxide surfaces with tailored functionality. The nanoparticles are stable and easily dispersed in both polar and nonpolar solvents, a property that is controlled by the ligand. The resultant nanoparticles were characterized by TEM, TGA, FTIR, and NMR.
EFFECTS OF VENTILATION ON HYALURONAN AND PROTEIN CONCENTRATION IN PLEURAL LIQUID OF ANESTHETIZED AND CONSCIOUS RABBITS

The hypothesis of this study is that pleural lubrication is enhanced by hyaluronan acting as a boundary lubricant in pleural liquid and by pleural filtration as reflected in changes in protein concentration with ventilation. Anesthetized rabbits were injected intravenously with Evans blue dye and ventilated with 100% O2 at either of two levels of ventilation for 6 h. Postmortem values of hyaluronan, total protein, and Evans blue-dyed albumin (EBA) concentrations in pleural liquid were greater at the higher ventilation, consistent with increases in boundary lubrication, pleural membrane permeability, and pleural filtration. To determine whether these effects were caused by hyperoxia or anesthesia, conscious rabbits were ventilated with either 3% CO2 or room air in a box for 6, 12, or 24 h. Similar to the anesthetized rabbits, pleural liquid hyaluronan concentration after 24 h was higher in the conscious rabbits with the hypercapnic-induced greater ventilation. By contrast, the time course of total protein and EBA in pleural liquid was similar in both groups of conscious rabbits, indicating no effect of ventilation on pleural permeability. The increase in pleural liquid hyaluronan concentration might be the result of mesothelial cell stimulation by a ventilation-induced increase in pleural liquid shear stress.
Definitions Of Chaos And Measuring Its Characteristics

The topic of this symposium is Optical Chaos. It is essential for those working in this field to know how to recognize, identify and characterize chaotic behavior and how to distinguish it from noise. General principles, definitions of terminology, and some brief review and commentary on the current status of techniques for measuring chaos are presented.
Direct Observation of Adsorption Evolution and Bonding Configuration of TMAA on TiO2(110)

Trimethylacetic acid (TMAA) adsorption evolution on the rutile TiO2(110) surface from submonolayer to saturation coverages was examined at the atomic level by scanning tunneling microscopy using the same area analysis approach. Upon TMAA deprotonation, no evidence of terminal OH group formation has been found. It has been suggested that uncommon geometry associated with detached hydrogen atom takes place instead, with proton bonding to pair bridging oxygen atoms. Such a configuration is likely to be stabilized by adjacent adsorbed TMA groups and, in turn, be a factor in the formation of TMA (2 × 1) reconstruction at saturation coverage. It also shown that the surface defects do not have a major impact on TMAA adsorption.
Restraint procedures and dementia sufferers with psychological trauma

Restraint is an extreme response to an emergency situation in which there is imminent harm to self or others. Although some restrained patients become calm, others may become even more behaviorally disorganized. In some of these latter cases, the restrained patients may be victims of violence for whom the restraint procedure acts as a symbolic reminder of the past victimization. Elderly dementia sufferers may also be among these victims of violence. This paper provides a brief review of psychological trauma, research findings on psychological trauma in the elderly, and an approach to modifying restraint procedures that may be needed for dementia sufferers with a past history of victimization to minimize the disquiet associated with the needed restraint.
A Low-Power 1-V Potentiostat for Glucose Sensors

In this brief, a 1-V potentiostat circuit for a glucose sensor has been proposed. Test results of this 1-V potentiostat demonstrate high linearity with respect to glucose concentration, which is comparable with conventional potentiostat designs. This high linearity is achieved with the help of a transconductance enhanced bulk-driven operational amplifier. The overall current consumption of the circuit is around 22 μA. The potentiostat is tested as a glucose biosensor for glucose concentration ranging from 0 to 30 mM. The design is realized in a 0.35-μm bulk-CMOS process, and the area for the core layout is 0.13 mm2. The proposed low-power potentiostat can be incorporated in an implantable glucose sensor system due to its low-power operation and small footprint.
Towards an Attribute Based Constraints Specification Language

Recently, attribute based access control (ABAC) has received considerable attention from the security community for its policy flexibility and dynamic decision making capabilities. In ABAC, authorization decisions are based on various attributes of entities involved in the access (e.g., users, subjects, objects, context, etc.). In an ABAC system, correct attribute assignment to different entities is necessary for ensuring appropriate access. Although considerable research has been conducted on ABAC, so far constraints specification on attribute assignment to entities has not been systematically studied in the literature. In this paper, we propose an attribute-based constraints specification language(ABCL) for expressing a variety of constraints on values that different attributes of various entities in the system can take. ABCL can be used to specify constraints on a single attribute or across multiple attributes of a particular entity. Furthermore, constraints on attributes assignment across multiple entities (e.g., attributes of different users) can also be specified. Finally, we demonstrate the usefulness of ABCL in practical usage scenarios including banking domains.
How Measurement Characteristics Can Affect ECERS-R Scores and Program Funding

This project involved examining the most widely used instrument designed to evaluate the quality of early learning environments, the Early Childhood Environment Rating Scale-Revised Edition (ECERS-R). There are many aspects related to the way that the ECERS-R is used in practice that can vary from one observation to the next. The method in which the ECERS-R is scored, the time point of the year in which the ECERS-R observations are conducted, the length of an observation period, and the start time of an observation are dependent entirely by the observer. However, there is little research on the susceptibility of the resulting scores to the influence of such measurement methods. Although the instrument developers can't possibly regulate exactly how the ECERS-R is used, it is important to know what the implications of these alternatives are. Using secondary data from over 250 classrooms, this article demonstrates how the effects of these measurement attributes can have important considerations for the polic...
Abstract LB-353: Development of thymidylate synthase ternary complex-specific antibody: A new way to tailor 5-fluorouracil dosing

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Introduction: 5-Fluorouracil (5FU) is a fluorinated nucleoside analogue used in cancer treatment. 5FU metabolites modify thymidylate synthase (TS) to form a ternary complex and inhibit its activity. Despite its benefits, major side effects are common and can lead to discontinuation of 5FU therapy. Although dose, schedule, and mode of application of 5FU can be adjusted to minimize toxicity, there has been a little done to tailor 5FU dosage for cancer therapy. Aims: To develop a ternary complex-specific monoclonal antibody. To develop a test quantifying drug-complexed TS level so as to measure the action of 5FU at the cellular level. Methods: Recombinant TS was produced in E. coli. In-vitro, the ternary complex was created. A specific rat monoclonal antibody was raised against drug-complexed TS. ELISA and immunoblot (IB) assays were validated using 5FU-treated cells. Tumors were developed in nude mice by injection of RKO and MiaPaCa2 cells. We treated tumors in mice with 5FU at different doses and assayed the tumor upon harvest. Results: The drug-complexed TS migrates slower than native TS in protein gels. Our novel ternary complex-specific rat monoclonal antibody (10C4) specifically recognized drug-complexed TS in ELISA and IB in both cultured cells and tumors treated with 5FU. Commercially available TS-specific antibody recognized both forms of TS. Conclusion: We developed and characterized the first thymidylate synthase ternary complex-specific rat monoclonal antibody. Implications: Quantification of drug-complexed TS may be possible with use of the new antibody. The actual action of 5FU at the cellular level can now be determined readily. It may become possible to calculate individualized 5FU doses in the clinic using advances in the technology. Such developments might decrease the incidence of toxicity and increase drug effectiveness during 5FU treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-353. doi:1538-7445.AM2012-LB-353
Effects of dietary fish oil on renal growth and function in uninephrectomized rats.

Effects of dietary fish oil on renal growth and function in uninephrectomized rats. The basic mechanisms of renal growth remain poorly understood. The work hypertrophy theory holds that after an acute reduction in renal mass, the growth of the kidney occurs as a consequence of increased renal function. Pharmacological inhibition of renal prostaglandin synthesis impairs the acute adaptive increases in both renal function and mass following partial nephrectomy. The present study examines the effects of four weeks of dietary fish oil on renal growth, function and arachidonic acid metabolites in intact and uninephrectomized male Sprague-Dawley rats. Dietary fish oil interferes with dienoic prostaglandin and thromboxane production in favor of synthesis of trienoic analogues. Control animals were pair-fed an identical diet with the exception that the fat was replaced by beef tallow. Renal cortical concentrations of arachidonic acid metabolites were reduced in animals fed fish oil, and urinary excretion of prostaglandin E 2 was impaired. Fish oil feeding resulted in increased kidney weight without concomitant increases in renal function in intact animals. Glomerular filtration rate and renal plasma flow were greater in uninephrectomized rats fed fish oil compared to uninephrectomized controls pair-fed beef tallow. Augmentation of the compensatory increases in renal function observed with fish oil feeding was not associated with any additional renal hypertrophy. These data indicate that dietary fish oil has a profound impact on renal growth and function, which may be the consequence of altered renal and/or extrarenal arachidonic acid metabolism. Furthermore, the direction of the alterations in renal mass oppose that of renal function, providing clear and unique evidence against the work hypertrophy theory of renal growth.
Comparison of forward (ear-canal) and reverse (round-window) sound stimulation of the cochlea

The cochlea is normally driven with “forward” stimulation, in which sound is introduced to the ear canal. Alternatively, the cochlea can be stimulated at the round window (RW) using an actuator. During RW “reverse” stimulation, the acoustic flow starting at the RW does not necessarily take the same path as during forward stimulation. To understand the differences between forward and reverse stimulation, we measured ear-canal pressure, stapes velocity, RW velocity, and intracochlear pressures in scala vestibuli (SV) and scala tympani (ST) of fresh human temporal bones. During forward stimulation, the cochlear drive (differential pressure across the partition) results from the large difference in magnitude between the pressures of SV and ST, which occurs due to the high compliance of the RW. During reverse stimulation, the relatively high impedance of the middle ear causes the pressures of SV and ST to have similar magnitudes, and the differential pressure results primarily from the difference in phase of the pressures. Furthermore, the sound path differs between forward and reverse stimulation, such that motion through a third window is more significant during reverse stimulation. Additionally, we determined that although stapes velocity is a good estimate of cochlear drive during forward stimulation, it is not a good measure during reverse stimulation. This article is part of a Special Issue entitled “MEMRO 2012”.
FDTD analysis of 100% efficient polarization-independent liquid crystal polarization grating

We report a numerical analysis of the liquid crystal polarization grating (LCPG) as an electro-optically controlled, polarization independent light modulator. The 2D finite-difference time-domain (FDTD) modeling for periodic anisotropic structures has been developed as a numerical tool to study optical properties of anisotropic gratings. Both normal and oblique incidence cases are successfully implemented for wide-band analysis. Nematic director profiles of the LCPG are obtained from elastic free-energy calculations using a commercial software tool, called LC3D. A study of the essential diffraction characteristics of the LCPG is presented, which manifests pixel-level light modulation with a nearly 100% efficiency on unpolarized light. The effect of an off-axis input and the grating regime on the LCPG diffraction is investigated. Finally, we present a study of the electro-optical response of the LCPG when an electric field applied for both static and dynamic cases. The FDTD results show that a highly efficient, polarization-independent light modulation with capability of an electrical switching/tuning is possible by the LCPG.
Functional Implications of a Newly Characterized Pathway of 11,12-Epoxyeicosatrienoic Acid Metabolism in Arterial Smooth Muscle

Epoxyeicosatrienoic acids (EETs) are potent vasodilators derived from cytochrome P-450 metabolism of arachidonic acid. The rapid conversion of EETs to their corresponding dihydroxyeicosatrienoic acids (DHETs) has been proposed as a process whereby EETs are rendered biologically inactive. However, the vascular metabolism of EETs and the vasoactivities of EET metabolites have not been extensively studied. Accordingly, 11,12-EET metabolism was characterized in porcine aortic smooth muscle cells. The cells converted [3H]11,12-EET to 11,12-DHET and to a newly identified metabolite, 7,8-dihydroxy-hexadecadienoic acid (DHHD). 11,12-DHET accumulation in the medium reached a maximum in 2 to 4 hours and then declined, whereas 7,8-DHHD accumulation increased continuously and exceeded the amount of 11,12-DHET by 8 hours. [3H]11,12-EET conversion to radiolabeled 7,8-DHHD was reduced in the presence of unlabeled 11,12-DHET, indicating that 11,12-DHET is an intermediate in the conversion of 11,12-EET to 7,8-DHHD. This is consistent with a pathway whereby 11,12-EET is converted by an epoxide hydrolase to 11,12-DHET, which then undergoes two beta-oxidations to form 7,8-DHHD. In porcine coronary artery rings contracted with a thromboxane mimetic, 11,12-DHET produced relaxation similar in magnitude to that produced by 11,12-EET (77% versus 64% relaxation at 5 mumol/L, respectively). 7,8-DHHD also produced vasorelaxation. Thus, the vasoactivity of 11,12-EET is not eliminated by conversion to 11,12-DHET and 7,8-DHHD. These results suggest that 11,12-DHET and its metabolite, 7,8-DHHD, may contribute to the regulation of vascular tone in the porcine coronary artery and possibly other vascular tissues.
Noninvasive Testing in Peripheral Arterial Disease

Most patients suspected of having peripheral arterial disease should undergo noninvasive vascular testing to confirm the diagnosis, and to determine the severity and extent of the disease. This article reviews practical aspects of commonly used noninvasive tests for lower extremity peripheral arterial disease, including the ankle-brachial index, segmental limb pressures, pulse volume recordings, duplex ultrasonography, computed tomography angiography, and magnetic resonance angiography.
Validating a Method to Identify At-Risk Middle School Students for Participation in a Dropout Prevention Program:

The study investigated the accuracy of identifying middle school students at risk of failing, using data available to teachers by the first 6 weeks of school for 109 seventh grade students within a team grouping of five teachers. Specifically, the study supported the research hypotheses that the components of the at-risk rating method used (a combination of students' grade reports, conduct ratings, absences, disciplinary actions received, and teachers' at-risk rankings) significantly predicted the number of Fs received at the end of 18 weeks, was a stronger predictor of Fs using multiple rather than individual measures, and that such a rating scheme was concurrently valid with an academically at-risk rating generated by a weighted regression prediction equation.
Effect of nutritional status on the fatty acid composition of rat liver and cultured hepatocytes.

The lipid concentration and fatty acid composition of the whole liver and of cultured hepatocytes isolated from the livers of rats fed ad libitum (fed), fasted for 24 hr (fasted), or fasted for 48 hr and then refed a fat-free, high carbohydrate diet for 48 hr (refed) was studied. Hepatocytes were maintained as monolayer cultures in serum-free, lipid-free media and their fatty acid composition was analyzed at 3, 24, 48, 72 and 96 hr. The livers of fed animals, as well as their hepatocytes, contained less total lipid than those from animals on either of the other dietary regimes. Livers of fasted animals had three times the amount of lipid found in the livers of fed animals, and the livers of refed animals contained five times the amount of lipid as the livers of fed animals (all based on mg lipid/g wet weight of liver). The fatty acid composition of hepatocytes after 3 hr of culturing was very similar to that of fresh liver when compared in each of the dietary regimes. However, while the fatty acid compositions of livers and hepatocytes from fed and fasted animals were similar, the pattern in liver of refed animals was quite distinct from that of the fed animals. In the fed and fasted animals palmitic acid (16∶0), stearic acid (18∶0), oleic acid (18∶1[n-9]), linoleic acid (18∶2[n-6]) and arachidonic acid (20∶4[n-6]) were the major fatty acids of the liver; in refed animals 16∶0, palmitoleic acid (16∶1[n-7]), 18∶0, 18∶1(n-9) andcis-vaccenic acid (the n-7 isomer of oleic acid) were the major fatty acids. During maintenance in culture the 18∶1(n-9) content of the hepatocytes increased in cells from livers of animals on all three dietary regimes. The polyunsaturated fatty acid content was similar in fresh livers and isolated hepatocytes in all samples when compared on the basis of μg fatty acid/mg of hepatocyte or liver protein. It was also found that the polyunsaturated fatty acid content of hepatocytes was remarkedly stable with time of culture when the cells were incubated in serum-free, lipid-free medium. Thus, isolated hepatocytes maintained in serum-free medium appear to be a possible system for the evaluation of the effects of prior nutritional status on fatty acid metabolism in the whole animal, not subject to hormonal and other somatic influences which often complicate the interpretation of such nutritional studies.
Catabolic enzyme activities in relation to premigratory fattening and muscle hypertrophy in the gray catbird ( Dumetella carolinensis )

The flight muscles of the gray catbird (Dumetella carolinensis) were examined to determine if short term adjustments occur in the activity of key catabolic enzymes during preparation for long distance migration. The aerobic capacity of the pectoralis muscle as indicated by citrate synthase activity (CS) is among the highest reported for skeletal muscle (200 μmoles [min·g fresh mass]−1 at 25°C). The mass specific aerobic capacity as indicated by CS activity or cytochromec concentration does not change during premigratory fattening (Fig. 2) or in relation to the muscle hypertrophy that occurs concomitantly. The maintenance of mass specific aerobic capacity indicates that the total aerobic capacity increases in proportion to the increase in muscle size. The augmented potential for total aerobic power output is considered an adaptation to meet the increased power requirements of flight due to the increased body mass. Additionally, the capacity to oxidize fatty acids, as indicated by β-hydroxyacyl-CoA dehydrogenase activity, approximately doubles during premigratory fattening (from 35 to 70 μmoles [min·g fresh mass]−1 at 25°C; Fig. 1A). This adaptation should favor fatty acid oxidation, thereby sparing carbohydrate and prolonging endurance. The activity of phosphofructokinase, a key glycolytic enzyme, does not change before migration.
On the Lyapunov exponent of a harmonic oscillator driven by a finite-state Markov process

This paper considers the asymptotic behavior of the random harmonic oscillator driven by a Markov process with a finite-state space. For a certain choice of variables, the motion of the system follows circles in the plane, with jumps from one circle to another at random times. The Lyapunov exponent is expressed in terms of the equilibrium measure of a related Markov chain. The latter satisfies an integralequation whose form permits an easy derivation of estimates in various limiting cases. This is demonstrated by computing the first-order approximation in a limit of weak noise. It is shown how some of the results can be extended to a certain class of two-dimensional systems.
Molecular Photovoltaics and Surface Potentials at the Air-Water Interface

An experimental approach that directly measures light-induced electrostatic surface potentials at the gas−liquid interface using the combined techniques of the atomic force microscope and the scanning surface-potential microscope is presented. Photosystem I (PSI) reaction centers, one of the molecular photovoltaic structures of green plants, convert light energy into electrical energy. We report the orientation and measurement of light-induced photovoltages at the air−water interface by PSI solutions entrained in the pores of microchannel glass. The data indicate that illuminated PSI reaction centers reversed the sign of the water surface electrostatic potential from negative to positive and that additional illumination further increased the positive value of the potential. The sign of the light-induced photopotentials indicates that the reaction centers are oriented with their electron-transport vectors pointing toward the water phase. Electrostatic potentials as a function of PSI concentration are prese...
CONVERGENCE IN LOTKA-VOLTERRA TYPE DIFFUSIVE DELAY SYSTEMS WITHOUT DOMINATING INSTANTANEOUS NEGATIVE FEEDBACKS

This paper deals with the convergence aspect of diffusive delay Lotka-Volterra systems with infinite delays. It is well known that such a system has a globally asymptotically stable steady state if the negative feedbacks of the intraspecific competitions are dominant and instantaneous. It is shown here that such a globally asymptotically stable steady state continues to exist even if the instantaneous assumption is removed, provided that solutions of the system are eventually uniformly bounded and the delays involved in the intraspecific competitions are small. This work generalises several recent related ones.
Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia.

Context: Despite advances made in treating the positive symptoms of schizophrenia, treatment of negative symptoms remains an unmet therapeutic need. Adjunctive mirtazapine has shown promise for treatment of negative symptoms in several small clinical trials. Objective: To assess the efficacy of mirtazapine as an adjunctive treatment of negative symptoms in patients with chronic schizophrenia via meta-analysis. Data Sources: A systematic literature review of articles in English and Spanish was conducted in November 2011 by searching PubMed, the Cochrane Library, the Clinical Trial Registry of the NIH, and SIGLE (System for Grey Literature in Europe). Free text search terms for PubMed were “schizophrenia,” “negative symptoms” and “mirtazapine.” Publication date was not a limitation. Study Selection: Studies of people with schizophrenia/schizoaffective disorder were included in the meta-analysis if they were randomized, double-blind, and used the Positive and Negative Syndrome Scale (PANSS) as an outcome mea...
Dependable computing depends on structured fault tolerance

Fault tolerance is a fundamental technique for the attainment of dependable computing. This paper discusses a general paradigm for the design of fault-tolerant systems and illustrates it by a design paradigm for fault-tolerant software.
ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2

In mutant superoxide dismutase (SOD1)-linked amyotrophic lateral sclerosis (ALS), accumulation of misfolded mutant SOD1 in spinal cord mitochondria is thought to cause mitochondrial dysfunction. Whether mutant SOD1 is toxic per se or whether it damages the mitochondria through interactions with other mitochondrial proteins is not known. We previously identified Bcl-2 as an interacting partner of mutant SOD1 specifically in spinal cord, but not in liver, mitochondria of SOD1 mice and patients. We now show that mutant SOD1 toxicity relies on this interaction. Mutant SOD1 induces mitochondrial morphological changes and compromises mitochondrial membrane integrity leading to release of Cytochrome C only in the presence of Bcl-2. In cells, mouse and human spinal cord with SOD1 mutations, the binding to mutant SOD1 triggers a conformational change in Bcl-2 that results in the uncovering of its toxic BH3 domain and conversion of Bcl-2 into a toxic protein. Bcl-2 carrying a mutagenized, non-toxic BH3 domain fails to support mutant SOD1 mitochondrial toxicity. The identification of Bcl-2 as a specific target and active partner in mutant SOD1 mitochondrial toxicity suggests new therapeutic strategies to inhibit the formation of the toxic mutant SOD1/Bcl-2 complex and to prevent mitochondrial damage in ALS.