bluuebunny/crossref_metadata_2025 huggingface dataset:
MAXIMIZING THE HYPERPOLARIZABILITY OF ONE-DIMENSIONAL SYSTEMS
Authors: SZAFRUGA URSZULA B. , KUZYK MARK G. , WATKINS DAVID S.
Published: October 2010

Previous studies have used numerical methods to optimize the hyperpolarizability of a one-dimensional quantum system. These studies were used to suggest properties of one-dimensional organic molecules, such as the degree of modulation of conjugation, that could potentially be adjusted to improve the nonlinear-optical response. However, there were no conditions set on the optimized potential energy function to ensure that the resulting energies were consistent with what is observed in real molecules. Furthermore, the system was placed in a one-dimensional box with infinite walls, forcing the wavefunctions to vanish at the ends of the molecule. In the present work, the walls are separated by a distance much larger than the molecule's length; and, the variations of the potential energy function are restricted to levels that are more typical of a real molecule. In addition to being a more physically-reasonable model, our present approach better approximates the bound states and approximates the continuum states — which are usually ignored. We find that the same universal properties continue to be important for optimizing the nonlinear-optical response, though the details of the wavefunctions differ from previous results.
SECOND HARMONIC GENERATION IN ZnO NANORODS
Authors: DAS MALYAJ , RANA SHIVANI , SEN PRATIMA
Published: October 2010

A comparative study of the second harmonic generation in ZnO micro particles and nanorods has been experimentally studied by Kurtz technique using nanosecond pulsed Nd:YAG laser. The results have been theoretically explained by taking into account the quadrupole moment as well as surface nonlinearity. It was observed that the nanorods yield polarized second harmonic signal while the second harmonic signal obtained from the micro particles was unpolarized.
NOVEL LAGUERRE-GAUSSIAN BEAM IN STRONGLY NONLOCAL NONLINEAR MEDIA
Authors: YANG ZHENG-PING , ZHONG WEI-PING
Published: October 2010

We have found an approach to constructing a novel class of Laguerre-Gaussian (LG) beam using a superposition of the known single accessible soliton solutions. Choosing appropriate values of soliton parameter, one can make up novel LG beams, such as asymmetric necklace beams and gear beams. The shape of superposition beams can be controlled by picking different topological charges.
INVESTIGATIONS AND MIMICRY OF THE OPTICAL PROPERTIES OF BUTTERFLY WINGS
Authors: SUMMERS CHRISTOPHER J. , GAILLOT DAVY P. , CRNE MATIJA , BLAIR JOHN , PARK JUNG O. , SRINIVASARAO MOHAN , DEPARIS OLIVIER , WELCH VICTORIA , VIGNERON JEAN-POL
Published: October 2010

Structural color in Nature has been observed in plants, insects and birds, and has led to a strong interest in these phenomena and a desire to understand the mechanisms responsible. Of particular interest are the optical properties of butterflies. In this paper, we review three investigations inspired by the unique optical properties exhibited in a variety of butterfly wings. In the first investigation, conformal atomic layer depositions (ALDs) were used to exploit biologically defined 2D photonic crystal (PC) templates of Papilio blumei with the purpose of increasing the understanding of the optical effects of naturally formed dielectric architectures, and of exploring any novel optical effects. In the second study, it was demonstrated that faithful mimicry of Papilio palinurus can be achieved by physical fabrication methods through using breath figures to provide templates and ALD routines to enable optical properties. Finally, knowledge of the optical structure properties of the Princeps nireus butterfly has resulted in bioinspired designs to enhanced scintillator designs for radiation detection.
THREE-DIMENSIONAL LIGHT BULLETS IN CUBIC–QUINTIC MEDIA STABILIZED BY PERIODIC VARIATION OF DIFFRACTION AND DISPERSION
Authors: SUBHA P. A. , ABDULLAH K. K. , KURIAKOSE V. C.
Published: October 2010

We propose a dispersion-managed model with diffraction management for the stabilization of three-dimensional spatiotemporal solitons in bulk cubic–quintic media. The cubic–quintic nonlinear Schrödinger equation with periodically varying dispersion and diffraction has been studied using analytical and numerical methods. Variational analysis and the Kapitsa averaging method have been used to study the system analytically. The study has shown that periodically varying coefficients of diffraction and dispersion stabilizes the spatiotemporal solitons in cubic–quintic media.
OPTICALLY TRANSPARENT GLASS WITH VERTICALLY ALIGNED SURFACE Al2O3 NANOWIRES HAVING SUPERHYDROPHOBIC CHARACTERISTICS
Authors: KIM JIN-YEOL , NOH KUNBAE , CHOI CHULMIN , BRAMMER KARLA S. , LOYA MARIANA , CHEN LI-HAN , JIN SUNGHO
Published: October 2010

We have shown in this paper that the self-ordered pore structure of anodic aluminum oxide (AAO) can be utilized as a basis to conveniently form large-area Al2O3 nanowire arrays on a glass surface. An aluminum oxide nanowire array has been produced by aluminum film deposition on glass followed by anodization, then simple chemical etching. The glass surface as prepared is highly superhydrophobic, with a contact angle as high as 169°. The thinness (~ 340 nm) and vertical alignment of the aluminum oxide nanowires with empty spaces in-between essentially contribute to maintaining the optical transparency of the glass substrate. Interestingly, substantially suppressed UV transmission in the ~ 300–400 nm spectrum region was observed with the presence of the Al2O3 nanowires on the glass substrate. Such a durable surface ceramic nanowire structure can be useful for producing superhydrophobic, self-cleaning glasses with a variety of potential applications such as UV protecting glass windows for high rise buildings with reduced consumption of water and cleaning chemicals for positive environmental effects.
CHROMATICITY DEPENDENCE ON Eu CONCENTRATION IN Y2O3:Eu NANOPOWDERS
Authors: GANJKHANLOU YADOLAH , KAZEMZAD MAHMOOD , HESSARI FEREIDOUN ALIKHANI
Published: October 2010

Y2O3:Eu nanopowders were synthesized by urea combustion method containing different concentration of Eu . The synthesized Y2O3:Eu nanopowders were characterized by X-ray diffractometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), energy dispersive X-ray analysis (EDX) and photoluminescence spectroscopy (PL). The particle size was calculated to be in the range of 15–30 nm using Scherrer's formula. The Ia-3 structure of synthesized Y2O3:Eu nanopowders were confirmed with X-ray diffractometry. The crystallinity of Y2O3:Eu nanopowders were confirmed by SAED and TEM images. The 5D0–∑7F J (J = 0, 1, 2, 3) and 5 D 1–7 F 1 transitions bands were observed at 575–650 and 530–550 ranges in the photoluminescence spectrum. The concentration quenching was estimated to be about 5 mol% of Eu . The best chromaticity to the standard red color was observed with the sample containing 3 mol% of Eu .
MICROSTRUCTURAL EFFECTS ON MACROSCALE THERMAL PROPERTIES IN NANOFLUIDS
Authors: FAN JING , WANG LIQIU
Published: October 2010

The recent first-principle model shows that heat conduction in nanofluids can be diffusion-dominant or thermal-wave-dominant depending on their microscale physics (structures, properties and activities). As the first attempt of quantifying when and to what extent thermal waves become important, we numerically examine effects of particle–fluid conductivity ratio, particle shape, volume fraction and nondimensional particle–fluid interfacial area in the unit-cell on macroscale thermal properties for nanofluids consisting of in-line arrays of perfectly dispersed two-dimensional circular, square and hollow particles, respectively. In simple and perfectly dispersed nanofluids, the heat conduction is diffusion-dominant so the effective thermal conductivity can be predicted adequately by the mixture rule with the effect of particle shape and particle–fluid conductivity ratio incorporated into its empirical parameter. Thermal waves appear more likely at smaller particle–fluid conductivity ratio (< 1) and lower particle-volume-fraction, which agrees with the experimentally observed significant conductivity enhancement in the oil-in-water emulsion. The computed thermal conductivity predicts some experimental data in the literature very well and shows the sensitivity to the nondimensional particle–fluid interfacial area in the unit-cell.
In the Virtual Extension
Authors: CACM Staff
Published: October 2010

To ensure the timely publication of articles, Communications created the Virtual Extension (VE) to expand the page limitations of the print edition by bringing readers the same high-quality articles in an online-only format. VE articles undergo the same rigorous review process as those in the print edition and are accepted for publication on merit. The following synopses are from articles now available in their entirety to ACM members via the Digital Library.
Career opportunities
Authors: Hoffmann Leah
Published: October 2010

What are the job prospects for today's---and tomorrow's---graduates?
K--12 computational learning
Authors: Cooper Stephen , Pérez Lance C. , Rainey Daphne
Published: October 2010

Enhancing student learning and understanding by combining theories of learning with the computer's unique attributes.
Why isn't cyberspace more secure?
Authors: Brenner Joel F.
Published: October 2010

Evaluating governmental actions---and inactions---toward improving cyber security and addressing future challenges.
Sensor networks for the sciences
Authors: Welsh Matt
Published: October 2010

Lessons from the field derived from developing wireless sensor networks for monitoring active and hazardous volcanoes.
The case against data lock-in
Authors: Fitzpatrick Brian W. , Lueck JJ
Published: October 2010

Want to keep your users? Just make it easy for them to leave.
Sir, please step away from the ASR-33!
Authors: Kamp Poul-Henning
Published: October 2010

To move forward with programming languages we must first break free from the tyranny of ASCII.
FastTrack
Authors: Flanagan Cormac , Freund Stephen N.
Published: October 2010

Multithreaded programs are notoriously prone to race conditions. Prior work developed precise dynamic race detectors that never report false alarms. However, these checkers employ expensive data structures, such as vector clocks (VCs), that result in significant performance overhead.

This paper exploits the insight that the full generality of VCs is not necessary in most cases. That is, we can replace VCs with an adaptive lightweight representation that, for almost all operations of the target program, requires constant space and supports constant-time operations. Experimental results show that the resulting race detection algorithm is over twice as fast as prior precise race detectors, with no loss of precision.
Puzzled: Rectangles galore
Authors: Winkler Peter
Published: October 2010

Welcome to three new puzzles. Solutions to the first two will be published next month; the third is (as yet) unsolved. In each, the issue is how your intuition matches up with the mathematics.
Wide open spaces
Authors: Savage Neil
Published: October 2010

The U.S. Federal Communications Commission's decision to open frequencies in the broadcast spectrum could enable broadband networks in rural areas, permit smart electric grids, and more.
Learning Through Storytelling, Not Documents
Authors: Schank Roger C.
Published: October 2010

People write memos, create project plans, issue report upon report, but no one can keep up. Document management systems have been created in an attempt to handle all this traffic, but eventually these systems are overwhelmed with documents, and finding what you want is difficult if not impossible for the casual user. Columnist Roger Schank reminds us of the fundamental connection humans have to stories and why they could be so powerful if used properly in training and education.
Identifying e-Learning Technologists
Authors: Soyoz Sirin
Published: October 2010

Education has seen big changes, many of which have been technology-driven: the rise of online collaboration tools, the expanding role of e-learning, sophisticated learning-management systems, and new communication tools. There has been a greater need for learning technologists to step in and help communities benefit from technology. The role of learning technologists is essential to integrate new technologies and education. This article provides an overview of the role of learning technologists as a professional group.
Enable Project Bring Education, Training to Marginalized Learners
Authors: Little Bob
Published: October 2010

Providing learning and development opportunities to people who, for one reason or another, would not be able to access these opportunities any other way, has to be one of the most noble and beneficial uses of e-learning. Columnist Bob Little discusses a new initiative in the European Union known as the ENABLE project, which aims to find ways to bring e-learning to society's marginalized learners.
Novel DNA-Hybridization Biosensors for Studies of DNA Underwinding Caused by Herbicides and Pesticides
Authors: Stobiecka Magdalena , Coopersmith Kaitlin , Cutler Sara , Hepel Maria
Published: October 2010

Among sensors developed for the detection of environmental pollutants, the biosensors based on DNA recognition abilities play a special role. In this work, a DNA biosensor for the evaluation of DNA damage by toxic agents has been designed which is not based on the DNA biorecognition properties but rather on the sensitivity of the intercalator-probe uptake to the conformational alterations of DNA double-helix. The sensors have been tested to assess DNA alterations caused by an herbicide atrazine. We have found that incubation of the DNA biosensor in atrazine solutions results in the increased capacity of DNA towards binding of an intercalator probe Nile Blue. On the basis of this and other findings, the mechanism of atrazine interactions with DNA double-helix has been elucidated.
Comprehensive Study of Pd/GaN Metal-Semiconductor-Metal Hydrogen Sensors with Metal-Oxide Mixture
Authors: Huang Tze-Hsuan , Chen Shang-Fu , Chang Heng-Jui , Huang Kuo-Ming , Lee Yueh-Lin , Chu Yun-Han , Wu Chung-Hung , Lour Wen-Shiung , Wu Meng-Chyi
Published: October 2010

We demonstrate a metal-semiconductor-metal Pd/GaN hydrogen sensor with a porous-like mixture of Pd and SiO2. Beside the symmetrically bidirectional sensing characteristics with a widespread voltage regime ranging at least from −5 to 5 V, a high sensing response of 8 × 105 and 7.7 × 106 corresponding to a Schottky barrier height variation of 352 and 411 meV is obtained in a 4890-ppm H2/N2 ambience at a voltage of −1.5 and −5 V, respectively. A highly efficient dissociation of hydrogen molecules due to an enhanced catalytic activity of the mixture explains the improved performance. Furthermore, dynamic responses by alternately switching the voltage polarity and introducing and removing hydrogen-containing gases are also included to evaluate the proposed device as a high sensing response and low power sensor. These statements are an example of what a properly prepared meeting abstract should look like. Proper column and margin measurements are also indicated.
Angiotensin-(1–7) increases neuronal potassium current via a nitric oxide-dependent mechanism
Authors: Yang Rui-Fang , Yin Jing-Xiang , Li Yu-Long , Zimmerman Matthew C. , Schultz Harold D.
Published: October 2010

Actions of angiotensin-(1–7) [Ang-(1–7)], a heptapeptide of the renin-angiotensin system, in the periphery are mediated, at least in part, by activation of nitric oxide (NO) synthase (NOS) and generation NO·. Studies of the central nervous system have shown that NO· acts as a sympathoinhibitory molecule and thus may play a protective role in neurocardiovascular diseases associated with sympathoexcitation, such as hypertension and heart failure. However, the contribution of NO in the intraneuronal signaling pathway of Ang-(1–7) and the subsequent modulation of neuronal activity remains unclear. Here, we tested the hypothesis that neuronal NOS (nNOS)-derived NO· mediates changes in neuronal activity following Ang-(1–7) stimulation. For these studies, we used differentiated catecholaminergic (CATH.a) neurons, which we show express the Ang-(1–7) receptor (Mas R) and nNOS. Stimulation of CATH.a neurons with Ang-(1–7) (100 nM) increased intracellular NO levels, as measured by 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence and confocal microscopy. This response was significantly attenuated in neurons pretreated with the Mas R antagonist (A-779), a nonspecific NOS inhibitor (nitro-l-arginine methyl ester), or an nNOS inhibitor ( S-methyl-l-thiocitrulline, SMTC), but not by endothelial NOS (eNOS) or inhibitory NOS (iNOS) inhibition {l- N-5-(1-iminoethyl)ornithine (l-NIO) and 1400W, respectively}. To examine the effect of Ang-(1–7)-NO· signaling on neuronal activity, we recorded voltage-gated outward K+ current ( IKv) in CATH.a neurons using the whole cell configuration of the patch-clamp technique. Ang-(1–7) significantly increased IKv, and this response was inhibited by A-779 or S-methyl-l-thiocitrulline, but not l-NIO or 1400W. These findings indicate that Ang-(1–7) is capable of increasing nNOS-derived NO· levels, which in turn, activates hyperpolarizing IKv in catecholaminergic neurons.
Glucose transport by human renal Na+/d-glucose cotransporters SGLT1 and SGLT2
Authors: Hummel Charles S. , Lu Chuan , Loo Donald D. F. , Hirayama Bruce A. , Voss Andrew A. , Wright Ernest M.
Published: October 2010

The human Na+/d-glucose cotransporter 2 (hSGLT2) is believed to be responsible for the bulk of glucose reabsorption in the kidney proximal convoluted tubule. Since blocking reabsorption increases urinary glucose excretion, hSGLT2 has become a novel drug target for Type 2 diabetes treatment. Glucose transport by hSGLT2 was studied at 37°C in human embryonic kidney 293T cells using whole cell patch-clamp electrophysiology. We compared hSGLT2 with hSGLT1, the transporter in the straight proximal tubule (S3 segment). hSGLT2 transports with surprisingly similar glucose affinity and lower concentrative power than hSGLT1: Na+/d-glucose cotransport by hSGLT2 was electrogenic with apparent glucose and Na+ affinities of 5 and 25 mM, and a Na+:glucose coupling ratio of 1; hSGLT1 affinities were 2 and 70 mM and coupling ratio of 2. Both proteins showed voltage-dependent steady-state transport; however, unlike hSGLT1, hSGLT2 did not exhibit detectable pre-steady-state currents in response to rapid jumps in membrane voltage. d-Galactose was transported by both proteins, but with very low affinity by hSGLT2 (≥100 vs. 6 mM). β-d-Glucopyranosides were either substrates or blockers. Phlorizin exhibited higher affinity with hSGLT2 ( Ki 11 vs. 140 nM) and a lower Off-rate (0.03 vs. 0.2 s−1) compared with hSGLT1. These studies indicate that, in the early proximal tubule, hSGLT2 works at 50% capacity and becomes saturated only when glucose is ≥35 mM. Furthermore, results on hSGLT1 suggest it may play a significant role in the reabsorption of filtered glucose in the late proximal tubule. Our electrophysiological study provides groundwork for a molecular understanding of how hSGLT inhibitors affect renal glucose reabsorption.
Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets
Authors: Miyata Toshio , Takizawa Shunya , van Ypersele de Strihou Charles
Published: October 2010

A variety of human disorders, e.g., ischemic heart disease, stroke, kidney disease, eventually share the deleterious consequences of a common, hypoxic and oxidative stress pathway. In this review, we utilize recent information on the cellular defense mechanisms against hypoxia and oxidative stress with the hope to propose new therapeutic tools. The hypoxia-inducible factor (HIF) is a key player as it activates a broad range of genes protecting cells against hypoxia. Its level is determined by its degradation rate by intracellular oxygen sensors prolyl hydroxylases (PHDs). There are three different PHD isoforms (PHD1–3). Small molecule PHD inhibitors improve hypoxic injury in experimental animals but, unfortunately, may induce adverse effects associated with PHD2 inhibition, e.g., angiogenesis. As yet, no inhibitor specific for a distinct PHD isoform is currently available. Still, the specific disruption of the PHD1 gene is known to induce hypoxic tolerance, without angiogenesis and erythrocytosis, by reprogramming basal oxygen metabolism with an attendant decreased oxidative stress in hypoxic mitochondria. A specific PHD1 inhibitor might therefore offer a novel therapy against hypoxia. The nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulates the basal and inducible expression of numerous antioxidant stress genes. Disruption of its gene exacerbates oxidative tissue injury. Nrf2 activity is modulated by Kelch-like ECH-associated protein 1 (Keap1), an intracellular sensor for oxidative stress. Inhibitors of Keap 1 may prove therapeutic against oxidative tissue injury.
Glut4 is upregulated despite decreased insulin signaling during prolonged fasting in northern elephant seal pups
Authors: Viscarra Jose A. , Vázquez-Medina José Pablo , Crocker Daniel E. , Ortiz Rudy M.
Published: October 2010

Postprandial cellular glucose uptake is dependent on an insulin-signaling cascade in muscle and adipose tissue, resulting in the translocation of the insulin-dependent glucose transporter 4 (Glut4) into the plasma membrane. Additionally, extended food deprivation is characterized by suppressed insulin signaling and decreased Glut4 expression. Northern elephant seals are adapted to prolonged fasts characterized by high levels of plasma glucose. To address the hypothesis that the fasting-induced decrease in insulin is associated with reduced insulin signaling in prolonged fasted seals, we compared the adipose protein levels of the cellular insulin-signaling pathway, Glut4 and plasma glucose, insulin, cortisol, and adiponectin concentrations between Early ( n = 9; 2–3 wks postweaning) and Late ( n = 8; 6–8 wks postweaning) fasted seals. Plasma adiponectin (230 ± 13 vs. 177 ± 11 ng/ml), insulin (2.7 ± 0.4 vs. 1.0 ± 0.1 μU/ml), and glucose (9.8 ± 0.5 vs. 8.0 ± 0.3 mM) decreased, while cortisol (124 ± 6 vs. 257 ± 30 nM) doubled with fasting. Glut4 increased (31%) with fasting despite the significant decreases in the cellular content of phosphatidylinositol 3-kinase as well as phosphorylated insulin receptor, insulin receptor substrate-1, and Akt2. Increased Glut4 may have contributed to the decrease in plasma glucose, but the decrease in insulin and insulin signaling suggests that Glut4 is not insulin-dependent in adipose tissue during prolonged fasting in elephant seals. The reduction of plasma glucose independent of insulin may make these animals an ideal model for the study of insulin resistance.
Glyceraldehyde 3-phosphate dehydrogenase is required for band 3 (anion exchanger 1) membrane residency in the mammalian kidney
Authors: Su Ya , Blake-Palmer Katherine G. , Fry Andrew C. , Best Alison , Brown Alice C. N. , Hiemstra Thomas F. , Horita Shoko , Zhou Aiwu , Toye Ashley M. , Karet Fiona E.
Published: October 2010

The mammalian kidney isoform of the essential chloride-bicarbonate exchanger AE1 differs from its erythrocyte counterpart, being shorter at its N terminus. It has previously been reported that the glycolytic enzyme GAPDH interacts only with erythrocyte AE1, by binding to the portion not found in the kidney isoform. (Chu H, Low PS. Biochem J 400:143–151, 2006). We have identified GAPDH as a candidate binding partner for the C terminus of both AE1 and AE2. We show that full-length AE1 and GAPDH coimmunoprecipitated from both human and rat kidney as well as from Madin-Darby canine kidney (MDCK) cells stably expressing kidney AE1, while in human liver, AE2 coprecipitated with GAPDH. ELISA and glutathione S-transferase (GST) pull-down assays using GST-tagged C-terminal AE1 fusion protein confirmed that the interaction is direct; fluorescence titration revealed saturable binding kinetics with Kd2.3 ± 0.2 μM. Further GST precipitation assays demonstrated that the D902EY residues in the D902EYDE motif located within the C terminus of AE1 are important for GAPDH binding. In vitro GAPDH activity was unaffected by C-terminal AE1 binding, unlike in erythrocytes. Also, differently from red cell N-terminal binding, GAPDH-AE1 C-terminal binding was not disrupted by phosphorylation of AE1 in kidney AE1-expressing MDCK cells. Importantly, small interfering RNA knockdown of GAPDH in these cells resulted in significant intracellular retention of AE1, with a concomitant reduction in AE1 at the cell membrane. These results indicate differences between kidney and erythrocyte AE1/GAPDH behavior and show that in the kidney, GAPDH is required for kidney AE1 to achieve stable basolateral residency.
Chronic vasodilation produces plasma volume expansion and hemodilution in rats: consequences of decreased effective arterial blood volume
Authors: Fekete Andrea , Sasser Jennifer M. , Baylis Chris
Published: October 2010

Plasma volume (PV) expansion is required for optimal pregnancy outcomes; however, the mechanisms responsible for sodium and water retention in pregnancy remain undefined. This study was designed to test the “arterial underfill hypothesis” of pregnancy which proposes that an enlarged vascular compartment (due to systemic vasodilation and shunting of blood to the placenta) results in renal sodium and water retention and PV expansion. We produced chronic vasodilation by 14 days administration of nifedipine (NIF; 10 mg·kg−1·day−1) or sodium nitrite (NaNO2; 70 mg·kg−1·day−1) to normal, nonpregnant female Sprague-Dawley rats. Mean arterial pressure, monitored by telemetry, was reduced by both NIF and NaNO2 but was unchanged in control rats. At day 14, vasodilator treatment lowered hematocrit and increased PV (determined by Evans blue dye dilution). Plasma osmolarity (Posm), sodium (PNa), and total protein concentrations all fell. These responses resemble the responses to normal pregnancy with hemodilution, marked PV expansion, and decreased Posmand PNa. Our previous work indicates a role of increased inner medullary phosphodiesterase-5 (PDE5) in the sodium retention of pregnancy. Here, we found that inner medullary PDE5A mRNA and protein expression were increased by both NIF and NaNO2 treatment vs. control; however, neither renal cortical nor aortic PDE5 expression was changed by vasodilator treatment. We suggest that a primary, persistent vasodilation drives increased inner medullary PDE5 expression which facilitates continual renal Na retention causing “refilling” of the vasculature and volume expansion.
Basal lamina secreted by MDCK cells has size- and charge-selective properties
Authors: Ferrell Nicholas , Groszek Joseph , Li Lingyan , Smith Ross , Butler Robert S. , Zorman Christian A. , Roy Shuvo , Fissell William H.
Published: October 2010

The role electrical charge plays in determining glomerular permeability to macromolecules remains unclear. If the glomerular basement membrane (GBM) has any significant role in permselectivity, physical principles would suggest a negatively charged GBM would reject similarly charged more than neutral species. However, recent in vivo studies with negative and neutral glomerular probes showed the opposite. Whether this observation is due to unique characteristics of the probes used or is a general physiological phenomenon remains to be seen. The goal of this study was to use the basement membrane deposited by Madin-Darby canine kidney epithelial cells as a simple model of a biologically derived, negatively charged filter to evaluate size- and charge-based sieving properties. Fluorescein isothiocyanate-labeled carboxymethylated Ficoll 400 (FITC-CM Ficoll 400) and amino-4-methyl-coumarin-labeled Ficoll 400 (AMC Ficoll 400) were used as negatively charged and neutral tracer molecules, respectively, during pressure-driven filtration. Streaming potential measurement indicated the presence of fixed, negative charge in the basal lamina. The sieving coefficient for neutral Ficoll 400 decreased by ∼0.0013 for each 1-Å increment in solute radius, compared with a decrease of 0.0023 per Å for the anionic Ficoll 400. In this system, molecular charge played a significant role in determining the sieving characteristics of the membrane, pointing to solute charge as a potential contributor to GBM permselectivity.
Is caveolin involved in normal proximal tubule function? Presence in model PT systems but absence in situ
Authors: Zhuang Zhenjie , Marshansky Vladimir , Breton Sylvie , Brown Dennis
Published: October 2010

Kidney proximal tubule (PT) cells are specialized for the uptake and transport of ions, solutes, peptides, and proteins. These functions are often regulated by hormones that signal at the cell surface and are internalized by clathrin-mediated endocytosis. However, the caveolin/caveolae pathway has also been implicated in normal PT function, often based on data from isolated PTs or PT cells in culture. Although we reported previously that caveolae and caveolin 1 are not detectable in PTs in vivo, reports of caveolin expression and function in PT cells appear periodically in the literature. Therefore, we reexamined caveolin expression in PTs in vivo, in isolated “purified” PTs following collagenase digestion, and in cultured PT cells. Caveolin 1 and 2 protein, mRNA, or immunofluorescence was undetectable in PTs in vivo, but PT cell cultures expressed caveolin 1 and/or 2. Furthermore, caveolin 1 and 2 mRNAs were detected in isolated PTs along with the endothelial markers CD31 and ICAM1. In contrast, no caveolin or endothelial marker mRNAs were detectable in samples isolated from snap-frozen kidneys by laser cut microdissection, which eliminates contamination by other cell types. We conclude 1) caveolin 1 and 2 are not normally expressed by PT cells in situ, 2) caveolin expression is “activated” in cultured PT cells, 3) contamination with non-PT, caveolin-expressing cells is a potential source of caveolin 1 and 2 that must be taken into account when isolated PTs are used in studies to correlate expression of these proteins with PT function.
An Increase in Persistent Sodium Current Contributes to Intrinsic Neuronal Bursting After Status Epilepticus
Authors: Chen Shmuel , Su Hailing , Yue Cuiyong , Remy Stefan , Royeck Michel , Sochivko Dmitry , Opitz Thoralf , Beck Heinz , Yaari Yoel
Published: October 2010

Brain damage causes multiple changes in synaptic function and intrinsic properties of surviving neurons, leading to the development of chronic epilepsy. In the widely used pilocarpine–status epilepticus (SE) rat model of temporal lobe epilepsy (TLE), a major alteration is the marked increase in the fraction of intrinsically bursting CA1 pyramidal cells. Here we have differentiated between two types of bursting phenotypes: 1) bursting in response to threshold-straddling excitatory current pulses (low-threshold bursting) and 2) bursting only in response to suprathreshold stimuli (high-threshold bursting). Low-threshold bursting prevailed in 46.5% of SE-experienced neurons sampled 1–4 wk after pilocarpine-SE, but was rarely seen in control neurons (1.9%). As previously shown, it appeared to be driven predominantly by a T-type Ca2+current ( ICaT) in the apical dendrites. After blocking low-threshold bursting with Ni2+, the same neurons still manifested a high-threshold bursting phenotype. Another 40.1% of SE-experienced neurons displayed only a high-threshold bursting phenotype and the remaining 13.4% of these neurons were nonbursters. Altogether, high-threshold bursting prevailed in 86.6% of SE-experienced neurons, but only in 33.0% of control neurons. Several lines of evidence indicated that high-threshold bursting is driven by persistent Na+current ( INaP) at or near the soma. Congruently, INaPwas 1.5-fold larger in SE-experienced versus control neurons. We conclude that an increase in INaP, conjointly with an increase in ICaT, strongly contributes to the predominance of bursting phenotypes in CA1 pyramidal cells early after pilocarpine-SE and thus likely plays a role in the development of a chronic epileptic condition in this TLE model.
Dynamic Regulation of NMDA Receptor Transmission
Authors: Gambrill Abigail C. , Storey Granville P. , Barria Andres
Published: October 2010

N-methyl-d-aspartate receptors (NMDARs) are critical for establishing, maintaining, and modifying glutamatergic synapses in an activity-dependent manner. The subunit composition, synaptic expression, and some of the properties of NMDARs are regulated by synaptic activity, affecting processes like synaptic plasticity. NMDAR transmission is dynamic, and we were interested in studying the effect of acute low or null synaptic activity on NMDA receptors and its implications for synaptic plasticity. Periods of no stimulation or low-frequency stimulation increased NMDAR transmission. Changes became stable after periods of 20 min of low or no stimulation. These changes in transmission have a postsynaptic origin and are explained by incorporation of GluN2B-containing receptors to synapses. Importantly, periods of low or no stimulation facilitate long-term potentiation induction. Moreover, recovery after a weak preconditioning stimulus that normally blocks subsequent potentiation is facilitated by a nonstimulation period. Thus synaptic activity dynamically regulates the level of NMDAR transmission adapting constantly the threshold for plasticity.
Potentiation of Synaptic AMPA Receptors Induced by the Deletion of NMDA Receptors Requires the GluA2 Subunit
Authors: Lu Wei , Gray John A. , Granger Adam J. , During Matthew J. , Nicoll Roger A.
Published: October 2010

Deletion of N-methyl-d-aspartate receptors (NMDARs) early in development results in an increase in the number of synaptic AMPA receptors (AMPARs), suggesting a role for NMDARs in negatively regulating AMPAR trafficking at developing synapses. Substantial evidence has shown that AMPAR subunits function differentially in AMPAR trafficking. However, the role of AMPAR subunits in the enhancement of AMPARs following NMDAR ablation remains unknown. We have now performed single-cell genetic deletions in double-floxed mice in which the deletion of GluN1 is combined with the deletion of GluA1 or GluA2. We find that the AMPAR enhancement following NMDAR deletion requires the GluA2 subunit, but not the GluA1 subunit, indicating a key role for GluA2 in the regulation of AMPAR trafficking in developing synapses.
TNFα Mechanically Sensitizes Masseter Muscle Nociceptors by Increasing Prostaglandin E2 Levels
Authors: Hakim Akhlaq W. , Dong Xudong , Cairns Brian E.
Published: October 2010

TNFα induces mechanical sensitization of rat masseter muscle nociceptors, which takes 2–3 h to manifest and is mediated through activation of P55 and P75 receptors. This study was undertaken to determine whether TNFα induces nociceptor mechanical sensitization through the release of other algogenic substances such as glutamate, prostaglandin E2 (PGE2), and/or nerve growth factor (NGF), which have been shown to induce mechanical sensitization of muscle nociceptors. Masseter muscle homogenate levels of PGE2 and NGF were measured 3 h after injection of TNFα (1 μg) or vehicle control using commercially available kits. Interstitial glutamate concentration was measured after injection of TNFα or vehicle control using a glutamate-selective biosensor probe. Diclofenac, a cycloxygenase inhibitor that blocks the synthesis of PGE2, d-2-amino-5-phophonovaleric acid (APV), a competitive N-methyl-d-aspartate (NMDA) receptor antagonist, and a tyrosine kinase A (TrkA) receptor antibody, which blocks NGF-induced masseter muscle nociceptor sensitization, were used to assess the contribution of PGE2, glutamate, and NGF to TNFα-induced nociceptor sensitization. PGE2 and glutamate concentrations were significantly elevated 3 h after TNFα injection into the masseter muscle. Injection of diclofenac partially reversed the TNFα-induced decreases in the mechanical threshold (MT) of masseter muscle nociceptors, whereas vehicle control, APV, and TrkA antibody did not significantly alter nociceptor MT. These results suggest that TNFα-induced mechanical sensitization of masseter muscle nociceptors is mediated in part by increased PGE2 levels. The findings of this study support the hypothesis that TNFα induces a delayed mechanical sensitization of masseter muscle nociceptors indirectly by the release of PGE2.
Keratouveitis as a First Presentation of Relapsing Polychondritis
Authors: Sallam Ahmed , Islam Tahmina , Parmar Dipak N.
Published: October 2010

This paper provides images and a description of an unusual manifestation of relapsing polychondritis presenting initially with isolated ocular signs, mimicking infective keratitis. We present an interventional case report of a 75-year-old man who presented with marked left ocular irritation and photophobia. Ophthalmological examination disclosed corneal intrastromal infiltrate and hypopyon which failed to respond to intensive antimicrobial drops. He later went on to develop bilateral auricular chondritis. Relapsing polychondritis was diagnosed. Treatment with topical and oral corticosteroids resulted in marked improvement of the corneal infiltrate and resolution of the auricular inflammation. The paper highlights the importance of considering connective tissue inflammatory conditions in any stromal keratitis unresponsive to antimicrobial treatment.
Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer
Authors: Scaiewicz V. , Sorin V. , Fellig Y. , Birman T. , Mizrahi A. , Galula J. , Abu-lail R. , Shneider T. , Ohana P. , Buscail L. , Hochberg A. , Czerniak A.
Published: October 2010

Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The H19 gene is an oncofetal RNA expressed during embryo development and in several types of cancer. We tested the expression of H19 gene in patients, and found that 65% of human pancreatic tumors analyzed showed moderated to strong expression of the gene. In vitro experiments showed that the vector was effective in reducing Luciferase protein activity on pancreatic carcinoma cell lines. In vivo experiment results revealed tumor growth arrest in different animal models for pancreatic cancer. Differences in tumor size between control and treated groups reached a 75% in the heterotopic model (P=.037) and 50% in the orthotopic model (P=.007). In addition, no visible metastases were found in the treated group of the orthotopic model. These results indicate that the treatment with the vector DTA-H19 might be a viable new therapeutic option for patients with unresectable pancreatic cancer.
Transcatheter Arterial Chemoembolization Is a Feasible Palliative Locoregional Therapy for Breast Cancer Liver Metastases
Authors: Cho Sung W. , Kitisin Krit , Buck David , Steel Jennifer , Brufsky Adam , Gillespie Roberta , Tsung Allan , Marsh James W. , Geller David A. , Gamblin T. Clark
Published: October 2010

Background. Liver metastases are common in advanced breast cancer. We sought to evaluate the role of transcatheter arterial chemoembolization (TACE) in breast cancer patients with hepatic metastases.Methods. A retrospective review of ten patients with breast cancer who were treated with TACE for unresectable liver metastases (1998–2008).Results. All patients, median age 46.5, had received prior systemic chemotherapies. Adriamycin was administered for 6, cisplatin/gemcitabine for 2, cisplatin for one and oxaliplatin for one patient. Median number of TACE cycles was 4. Kaplan Meier survival analysis showed an increase in median survival for patients who responded to treatment when compared to those who did not respond (24vs7 months,P=.02).Conclusions. This is one of the largest series of breast cancer patients with liver metastases treated with TACE. It suggests that TACE is a feasible palliative option and warrants further investigations.
Two New Iterative Methods for a Countable Family of Nonexpansive Mappings in Hilbert Spaces
Authors: Wang Shuang , Hu Changsong
Published: October 2010

We consider two new iterative methods for a countable family of nonexpansive mappings in Hilbert spaces. We proved that the proposed algorithms strongly converge to a common fixed point of a countable family of nonexpansive mappings which solves the corresponding variational inequality. Our results improve and extend the corresponding ones announced by many others.
Relationship between Fecal Content of Fatty Acids and Cyclooxygenase mRNA Expression and Fatty Acid Composition in Duodenal Biopsies, Serum Lipoproteins, and Dietary Fat in Colectomized Familial Adenomatous Polyposis Patients
Authors: Almendingen K. , Høstmark A. T. , Larsen L. N. , Fausa O. , Bratlie J. , Aabakken L.
Published: October 2010

A few familial adenomatous polyposis studies have focused upon faecal sterols and bile acids but none has analysed the fecal content of fatty acids. We report here findings of an observational study on 29 colectomized familial adenomatous polyposis patients that describe the fecal content of fatty acids, and relate this to the proportions of fatty acids and levels of cyclooxygenase mRNA expression in duodenal biopsies, levels of serum lipoproteins, and diet. In the ileostomy group separately (n=12), the fecal content of arachidonic acid was correlated negatively to the proportions of eicosapentaenoic acid and docosahexaenoic acid in duodenal biopsies. Total serum-cholesterol was negatively correlated to the fecal content of saturates and monounsaturates. The fecal palmitoleic acid/palmitic acid ratio was positively correlated to the levels of cyclooxygease-2 expression in duodenal biopsies.In the ileal-pouch-anal anastomosis group separately (n=17), significant correlations were found between the fecal contents of oleic acid, linoleic acid, and alpha-linolenic acid, and the proportions of myristic acid, oleic acid and eicosaenoic acid in duodenal biopsies. Dietary monounsaturates were positively correlated to different fecal fatty acids. Future studies should focus on molecular mechanisms relevant to fatty acid metabolism, inflammation, and angiogenesis, in addition to nutrition.
Herpesvirus BACs: Past, Present, and Future
Authors: Warden Charles , Tang Qiyi , Zhu Hua
Published: October 2010

The herpesviridae are a large family of DNA viruses with large and complicated genomes. Genetic manipulation and the generation of recombinant viruses have been extremely difficult. However, herpesvirus bacterial artificial chromosomes (BACs) that were developed approximately 10 years ago have become useful and powerful genetic tools for generating recombinant viruses to study the biology and pathogenesis of herpesviruses. For example, BAC‐directed deletion mutants are commonly used to determine the function and essentiality of viral genes. In this paper, we discuss the creation of herpesvirus BACs, functional analyses of herpesvirus mutants, and future applications for studies of herpesviruses. We describe commonly used methods to create and mutate herpesvirus BACs (such as site‐directed mutagenesis and transposon mutagenesis). We also evaluate the potential future uses of viral BACs, including vaccine development and gene therapy.
Small-Scale Spatial Analysis ofIn SituSea Temperature throughout a Single Coral Patch Reef
Authors: Gorospe Kelvin D. , Karl Stephen A.
Published: October 2010

Thermal stress can cause geographically widespread bleaching events, during which corals become decoupled from their symbiotic algae. Bleaching, however, also can occur on smaller, spatially patchy scales, with corals on the same reef exhibiting varying bleaching responses. Thus, to investigate fine spatial scale sea temperature variation, temperature loggers were deployed on a 4 m grid on a patch reef in Kāne'ohe Bay, Oahu, Hawai‘i to monitorin situ, benthic temperature every 50 minutes at 85 locations for two years. Temperature variation on the reef was characterized using several summary indices related to coral thermal stress. Results show that stable, biologically significant temperature variation indeed exists at small scales and that depth, relative water flow, and substrate cover and type were not significant drivers of this variation. Instead, finer spatial and temporal scale advection processes at the benthic boundary layer are likely responsible. The implications for coral ecology and conservation are discussed.
ING Genes Work as Tumor Suppressor Genes in the Carcinogenesis of Head and Neck Squamous Cell Carcinoma
Authors: Li Xiaohan , Kikuchi Keiji , Takano Yasuo
Published: October 2010

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. The evolution and progression of HNSCC are considered to result from multiple stepwise alterations of cellular and molecular pathways in squamous epithelium. Recently, inhibitor of growth gene (ING) family consisting of five genes,ING1toING5, was identified as a new tumor suppressor gene family that was implicated in the downregulation of cell cycle and chromatin remodeling. In contrast, it has been shown thatING1andING2play an oncogenic role in some cancers, this situation being similar to TGF-β. In HNSCC, theINGfamily has been reported to be downregulated, and ING translocation from the nucleus to the cytoplasm may be a critical event for carcinogenesis. In this paper, we describe our recent results and briefly summarize current knowledge regarding the biologic functions ofINGin HNSCC.
p38 Kinase Is Crucial for Osteopontin-Induced Furin Expression That Supports Cervical Cancer Progression
Authors: Kumar Vinit , Behera Reeti , Lohite Kirti , Karnik Swapnil , Kundu Gopal C
Published: October 2010

p38 kinases activated by growth factors, hormones, and environmental stresses exert diverse functions in regulating normal and malignant cell pathophysiology. Enhanced levels of activated p38 isoforms have been linked with poor prognosis in breast cancer, although the mechanistic basis for this association is poorly understood. In this study, we report that p38 activation in cervical cancer cells is driven by osteopontin (OPN), an extracellular matrix–associated cytokine that drives invasive progression. OPN regulates CD44-mediated p38 phosphorylation that induces NF-κB activation and NF-κB–dependent expression of furin, an extracellular protease implicated in human papilloma virus (HPV) processing that enhances cervical cancer cell motility. OPN induces CD44-mediated MKK3/6 phosphorylation which in turn phosphorylates p38 in these cells. OPN-induced furin expression and cell motility was impeded by blockades to MKK3/6, p38α/β or NF-κB signaling. In a mouse xenograft model of human cervical cancer, tumor growth was enhanced by OPN overexpression and blocked by short hairpin RNA (shRNA)–mediated OPN silencing. Furin overexpression similarly augmented tumor growth in the model, whereas blocking MKK3/6, p38, or furin reduced OPN-induced cervical tumor growth. Analysis of clinical specimens revealed that enhanced expression of OPN, phosphorylated NF-κB, p65, and furin correlated with cervical cancer progression, further strengthening the in vitro and in vivo results. In summary, our findings offer a proof of concept for targeting OPN and its downstream p38 signaling as a novel therapeutic strategy to manage cervical cancer. Cancer Res; 70(24); 10381–91. ©2010 AACR.