bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualization of Solution Chemistry inside Crevice by pH and pCl Sensing Plates
Authors: Kaji Takefumi , Sekiai Toshiya , Muto Izumi , Sugawara Yu , Hara Nobuyoshi
Published: May 2012

Both pH and pCl sensing plates were fabricated using ethyl violet (pH indicator) and quinine sulfate (fluorescent dye for pCl indicator). The sensing plates were also used for crevice formers. The crevice corrosion for 18Cr-10Ni-5.5Mn stainless steel was studied at 0.3 V (vs. Ag/AgCl, 3.33 M KCl) in 0.01 M NaCl solution (pH 3.0, 298 K). The pH inside the crevice gradually decreased with time, whereas chloride ion concentration did not change. An etch pit was initiated inside the crevice at the pH of 1.7 and the chloride ion concentration of 0.007 M. Just after the etch pit initiation, the pH of the surrounding area of the pit suddenly decreased to 0.4, the chloride ion concentration sharply increased to above 4 M. The dissolved metal ions from the etch pit led to increased acidification, and then the depassivation of the steel matrix occurred.
Growth and Morphology of Highly Ordered TiO2 Nanotube Arrays via Electrochemical Anodization
Authors: Liu Guohua , Hoivik Nils , Wang Kaiying , Jakobsen Henrik
Published: May 2012

In this paper, highly ordered titania nanotube arrays (TNTs) were prepared by anodization of Ti foils in ethylene glycol electrolyte. The morphology of the TNTs under different voltage and duration has been studied by Scanning Electron Microscopy (SEM). The constituent elements of the TNTs are mapped by energy dispersive X-ray (EDX). Immobilized TNTs were formed in the voltage range of 20~80V. High anodic voltage (>80V) induced detachable nanotube arrays on Ti foils. The nanotube diameter increases with increasing the applied voltage and without dependence on the anodic duration. The concentration of element oxygen is rich at top and bottom sections of the nanotube arrays. Meanwhile, the oxygen concentration on top surface decreases with increasing the anodization voltage.
Evaluating Real-Life Performance of Lithium-Ion Battery Packs in Electric Vehicles
Authors: Klass Verena , Behm Maårten , Lindbergh Göran
Published: May 2012

In regard to the increasing market launch of plug-in hybrid electric vehicles (PHEVs), understanding battery pack performance under electric vehicle (EV) operating conditions is essential. As lifetime still remains an issue for battery packs, it is a necessity to monitor the battery pack's state-of-health (SOH) on-board. Standard performance tests for health evaluation do not apply since operation interruptions and additional testing equipment are beyond question during ordinary EV usage. We suggest a novel methodology of performance estimation from real-life battery data. On the basis of battery pack data collected during PHEV operation, a support vector machine model is constructed that serves as source for performance evaluation figures. The SOH indicator "10 s discharge resistance" as known from hybrid pulse power characterization (HPPC) tests is chosen to exemplify how performance degradation can be followed over a year.
Sol Gel Dip Coated Indium Oxide Films and Their Properties
Authors: Ramanathan Govindarajan , Xavier R. John , Murali K. R.
Published: May 2012

Indium oxide films were deposited by the sol gel dip coating technique using Acrylamide route. The films were post heat treated in air at different temperatures in the range of 350 - 500åC for different durations in the range of 15 min to 90 min.The films possessed grain size in the range of 7 - 20 nm. The band gap of the films is in the range of 3.73 to 3.82 eV. The films had high transmission in the range of 86 to 88 %. The charge carrier density was around 1020 cm-3.
(Invited) Manufacturing of Hierarchical Composite Structures via Controlled Ceramic Nanoparticle Incorporation in Electrodeposited Thin Films
Authors: Farias Stephen L. , Young Austin , Lan TianLei , Breysse Patrick C. , Chien Chai-Ling , Cammarata Robert C.
Published: May 2012

Electrochemical deposition has continued to grow as an important industry tool not only for depositing traditional metal structures, but also for manufacturing more complex composite thin films. Previous work has demonstrated the ability to manufacture metal matrix composites with precisely controlled oxide nanoparticle incorporation using a rotating disk electrode (RDE) setup. In this method the speed of the RDE is used to directly control the rate of particle incorporation. It is feasible to manufacture higher order composite structures using this novel technique by simply varying the rotation rate of the RDE during deposition. Specific attention is given to periodically layered composite structures. These hierarchical structures are demonstrated with nanometer scale interface resolution and sub-micron to millimeter characteristic length scales (layer thicknesses). These ordered composites should yield unique mechanical properties compared to those of randomly dispersed composite structures, and have immediate industry applications.
Ultra-Low Copper Baths for Sub-35nm Copper Interconnects
Authors: Atanasova Tanya A. , Carbonell Laureen , Caluwaerts Rudy , Tokei Zsolt , Strubbe Katrien , Vereecken Philippe M.
Published: May 2012

The copper interconnect technology is constrained by the significant current distribution due to the terminal effect for resistive thin seeds. As a result, the current in the wafer center can become insufficient for cathodic protection of thin copper seeds leading to center seed corrosion. To improve the current distribution, the exchange current density can be lowered e.g. by lowering the copper concentration. Our approach is to investigate and develop acid ultra-low copper baths with feature fill capability. For this goal, the optimum additives concentrations were sought and fill studies in 30 nm trenches were performed. In addition, proposing a high acid chemistry that is also compatible with direct plating, would enable the in-situ copper seed formation and filling in one and the same process step for direct plating on non-copper seed.
Achieving Hydrogen Production through Solid Oxide Electrolyzer Stack by High Temperature Electrolysis
Authors: Jin Le , Guan Wan Bing , Ma Xiao , Xu Cheng , Wang Wei Guo
Published: May 2012

Based on the reversal reaction of solid oxide fuel cells (SOFC), high temperature electrolysis (HTE) is an effective way for large-scale and low cost hydrogen production. The problem restricted the development for HTE is the stability of steam supplying, conversion rate of steam to H2, hydrogen production rate and the durability of solid oxide electrolysis cells (SOECs) and stacks. To solve the problems mentioned above, a steam and gas fogged mixer (SGFM) was designed which can be used for not only experimental HTE but also large-scale hydrogen production. A 30-cell SOEC stack was tested combined with the mixer for 1000 hours at 800oC with an electrolysis current of 4 A. The steam-to-hydrogen conversion (SC) rate was calculated to be 70% by determining the water amount at the inlet and outlet of the hydrogen electrode. The hydrogen production rate was 99.3 NL/h.
Electrodeposition of CoMn onto Stainless Steels Interconnects for Increased Lifetimes in SOFCs
Authors: Hall Timothy D. , McCrabb Heather A. , Kell Joseph , Kagajwala Burhanuddin , Zhang Hui , Liu Xingbo , Taylor E. Jennings
Published: May 2012

A pulse and pulse reverse electrochemical deposition process is being developed for cost effective coating of solid oxide fuel cell (SOFC) interconnects. Faraday Technology and WVU demonstrated that the developed process could produce uniform dense, crack-free, well-adhered CoMn alloy coatings of various compositions on up to a 10 cm x 10 cm 441 stainless steel interconnect surface. The performance of various CoMn coatings has been evaluated before and after long duration thermal soak (~2000 hr @ 850°C) to determine the potential of each coating to mitigate Cr diffusion. The data included herein demonstrates the coatings potential while also identifying several challenges that need to be overcome before a successful coating can be scalably produce. Finally, we demonstrate the scalability of the FARADAYICSM Process via dual sided deposition of CoMn onto 10 cm x 10 cm T441 substrates.
Graphite Oxide with Different Oxygen Contents as Photocatalysts for Hydrogen and Oxygen Evolution from Water
Authors: Yeh Te-Fu , Teng Hsisheng
Published: May 2012

Graphite oxide (GO) photocatalysts were derived from graphite oxidation. Absorption spectroscopy shows the increasing band gap of GO with the oxygen content. Electrochemical analysis along with the Mott-Schottky equation show that the conduction and valence band edge levels of GO from appropriate oxidation are suitable for both the reduction and oxidation of water. The photocatalytic activity of GO specimens with various oxygen contents was measured in methanol and AgNO3 solutions for H2 and O2 evolution, respectively. The H2 evolution was strong and stable over time whereas the O2 evolution was negligibly small due to mutual photocatalytic reduction of the GO with upward shift of the valence band edge under illumination. The conduction band edge of GO showed negligibly change with the oxygen content. When NaIO3 was used as a sacrificial reagent to suppress the mutual reduction mechanism under illumination, strong O2 evolution was observed over the GO specimens. The present study demonstrates that chemical modification can easily modify the electronic properties of GO for specific photosynthetic applications.
Electrolyte Additive Chemistry and Feature Size-Dependent Impurity Incorporation for Cu Interconnects
Authors: Kelly James , Nogami Takeshi , Van der Straten O. , Demarest James , Li Juntao , Penny Chris , Vo Tuan , Parks Christopher , DeHaven Patrick , Hu Chao-Kun , Liniger Eric
Published: May 2012

The role of electrolyte additive chemistry in the incorporation of non-metallic impurities (such as C, S, and Cl) in electrodeposited Cu and its subsequent recrystallization behavior was characterized for both blanket electrodeposited Cu films and Cu plated into Damascene features. Chemistries yielding both pure and "doped" Cu were considered. For wide features (~ >1 μm), impurity levels correspond well with blanket Cu film observations, while for narrow features (~50 nm), impurity levels were elevated within the features, regardless of chemistry type. Recrystallization within Damascene features was observed to be relatively insensitive to the electrodeposited Cu purity and instead more dependent on feature size.
Self-Controlled Constant-Current Temperature Stress for Triangular Voltage Sweep Measurements of Cu
Authors: Ciofi Ivan , Mannarino Manuel , Li Yunlong , Croes Kristof , Beyer Gerald P.
Published: May 2012

We present a new methodology for the characterization of Cu diffusion barriers, which is based on Triangular Voltage Sweep (TVS) measurements of Cu+ after Constant-Current Temperature Stress (CCTS). We show that CCTS-TVS measurements are effective for identifying defective Cu diffusion barriers. Finally, we discuss about mechanisms of Cu+ drift into dielectrics.
Morphological Variation of Electrodeposited Li in Ionic Liquid
Authors: Nishikawa Kei , Naito Hitoshi , Kawase Makoto , Nishida Tetsuo
Published: May 2012

Li metal negative electrode is expected for the next-generation Li battery electrode material, and the control of morphological variation of the Li metal electrode surface is very important issue. In-situ observation of the Li dendrite growth in an ionic liquid by an optical microscope was done in order to discuss the relationship between the Li dendrite growth and the Li+ ionic mass transfer rate. Li dendrite growth in the ionic liquid starts before the surface Li+ ion concentration which is calculated by a simple model become zero. The development of the dendrite length shows the linearity with the square root of time, and this slope has a bending point just after the Li+ ion is depleted. These phenomena mean the Li+ ionic mass transfer rate is also an important parameter for the Li dendrite growth, as well as the surface state of the Li metal electrode.
Ionic Liquids: Potential Electrolytes for Lithium-Ion Batteries
Authors: Srour Hassan M. , Giroud Nelly , Rouault Helene , Santini Catherine C.
Published: May 2012

Ionic liquids present unique properties that make them interesting as a safer electrolyte for lithium ion batteries. In this work, we reported the electrochemical study, cyclic performance of neat 1-hexyl-3-methylimidazoliumbis(trifluoromethanesulfonyl)imide [C1C6Im][NTf2] and the binary mixture [Li][C1C6Im][NTf2] at 303 K in different concentrations of LiNTf2 ranging from 0 to 1.6 mol.L-1(M).
Tailoring a Desired Interphase on Graphitic Anode
Authors: Ho Janet , Xu Kang
Published: May 2012

In this work we attempted to tailor the chemistry at edge sites of graphite by metallic decoration, so that Li+-transport thereat could be accelerated to benefit a fast-charging graphitic anode.
Effect of Copper on the Dusting of Fe-Ni Alloys
Authors: Zhang Jianqiang , Young David J.
Published: May 2012

Model iron based alloys containing 20, 30, 40, 60, 80 wt% Ni and 0, 5 or 10 wt% Cu were used to investigate copper effects on alloy coking and dusting in a 68%CO-31%H2-1%H2O gas mixture (aC = 33, pO2 = 7.1×10-26 atm) at 650°C. Carbon uptake (coking) kinetics were measured thermogravimetrically, and dusting kinetics were evaluated by measuring metal corrosion depths. Additions of copper slowed both carbon uptake and metal dusting rates. However, at copper levels exceeding the solubility limit, dusting was accelerated. The effects of copper are discussed in terms of alterations to the graphite precipitation process.
Issues Concerning the Oxidation of Ni(Pt)Ti Shape Memory Alloys
Authors: Smialek James L.
Published: May 2012

The oxidation behavior of the Ni-30Pt-50Ti high temperature shape memory alloy is compared to that of conventional NiTi nitinol SMAs. The oxidation rates were ~1/4 those of NiTi under identical conditions. Ni-Ti-X SMAs are dominated by TiO2 scales, but, in some cases, the activation energy diverges for unexplained reasons. Typically, islands of metallic Ni or Pt(Ni) particles are embedded in lower scale layers due to rapid selective growth of TiO2 and low oxygen potential within the scale. The blocking effect of Pt-rich particles and lower diffusivity of Pt-rich depletion zones are proposed to account for the reduction in oxidation rates.
Oxidation Behavior of Stainless Steel 441 and 430 in Dual Atmosphere - Effects of Alloy Grain Boundaries
Authors: Zhao Yu , Fergus J. W.
Published: May 2012

The effects of alloy grain boundaries on the oxidation behaviors of alloy 430 and 441 in dual atmospheres (wet Ar-5vol% H2|35ml/min dry air) at 800ºC for 100, 200 and 400 hours were investigated. The samples with large grain size (430: 50µm and 441: 150 µm) were tested. For alloy 430, the surface of the scale formed on the air side area after 100 and 200hr of dual atmosphere oxidation contained many Fe-rich nodules along alloy grain boundaries. For alloy 441, all the oxide scales were composed mainly of a surface (Mn,Cr,Fe)3O4 spinel layer and a Cr2O3 sublayer. Only some isolated areas contained Fe-rich nodules on the air side of sample exposed to a dual atmosphere.
Electrochemically Deposition of High Mo Content Amorphous/Nanocrystalline Ni-Mo Using Ionic Liquids as Additive
Authors: Allahyarzadeh Mohammad Hossein , Roozbehani Behrooz , Ashrafi Ali , Shadizadeh Seyyed Reza , Kheradmand Ehsan
Published: May 2012

Ni-Mo alloy coatings containing more than 49 wt.% Mo have been electrodeposited onto mild steel from ammonia-citrate solution in the presence of two kind of imidazolium-based ionic liquids as additive. Pulse plating technique was employed for electrodeposition. The structural components of the coatings were evaluated employing X-ray diffraction method (XRD). Microstructure, morphology and chemical composition of the coatings were investigated using scanning electron microscopy (SEM) and X-ray energy-dispersive spectroscopy (EDX) analysis. SEM micrographs revealed different morphology of Ni-Mo electrodeposits in the presence of ionic liquids. Also XRD patterns illustrated that present conditions lead to deposit Ni-Mo coatings with amorphous/nanocrystalline structure. The results showed that, within the range of 30-35 wt.% Mo nanocrystalline Ni-Mo with the lowest grains size have been developed. Temperature and pH were varied to investigate their effects on deposited Ni-Mo film characteristics.
Pulse Electrodeposited CuInTe2 Films
Authors: Chandran Vinothini , Srinivas Srinivasan , Murali K. R.
Published: May 2012

Copper Indium Telluride films were deposited for the first time by the pulse electrodeposition technique at different duty cycles in the range of 6 - 50 % at room temperature and at a constant potential of -0.66V(SCE). The films exhibited single phase copper indium telluride. The grain size increased with increase of duty cycle. Optical band gap of the films varied in the range of 0.98 - 1.02 eV. Atomic force microscopy studies indicated that the grain size and surface roughness vary from 15 nm to 30 nm and 1.0 nm to 1.5 nm respectively with increase of duty cycle. Capacitance voltage measurements indicated the films to exhibit n-type behaviour. The flat band potential was - 0.76V(SCE) and carrier density was in the range of 1016 cm-3.
Hydrogen sulfide protects SH-SY5Y cells against 6-hydroxydopamine-induced endoplasmic reticulum stress
Authors: Xie Li , Tiong Chi Xin , Bian Jin-Song
Published: May 2012

Endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative diseases, including Parkinson's disease. The present study attempted to investigate the effect of hydrogen sulfide (H2S) on 6-hydroxydopamine (6-OHDA)-induced ER stress in SH-SY5Y cells. We found in the present study that exogenous application of sodium hydrosulfide (NaHS; an H2S donor, 100 μM) significantly attenuated 6-OHDA (50 μM)-induced cell death. NaHS also reversed the upregulation of cleaved poly(ADP-ribose) polymerase and caspase 9 in 6-OHDA-treated cells. Consistent with its cytoprotective effects, NaHS markedly reduced 6-OHDA induced-ER stress responses, including the upregulated levels of eukaryotic initiation factor-2α phosphorylation, glucose-regulated protein 78, and C/EBP homologous protein expression. The protective effect of H2S on ER stress was attenuated by blockade of Akt activity with an Akt inhibitor or inhibition of heat shock protein (Hsp)90 with geldanamycin but not by suppression of ERK1/2 with PD-98059. Blockade of Akt also significantly decreased the protein abundance of Hsp90 in SH-SY5Y cells. Moreover, overexpression of cystathionine β-synthase (a main H2S-synthesizing enzyme in the brain) elevated the Hsp90 protein level and suppressed 6-OHDA-induced ER stress. In conclusion, the protective effect of H2S against 6-OHDA-induced ER stress injury in SH-SY5Y cells involves the Akt-Hsp90 pathway.
Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice
Authors: Iwadate Reiko , Satoh Yoko , Watanabe Yukino , Kawai Hiroshi , Kudo Naomi , Kawashima Yoichi , Mashino Tadahiko , Mitsumoto Atsushi
Published: May 2012

It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. To examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (Tb) in a mouse model of porphyria with impaired heme biosynthesis by feeding mice a griseofulvin (GF)-containing diet. Mice fed with a 2.0% GF-containing diet (GF2.0) transiently exhibited phase advance or phase advance-like phenomenon by 1–3 h in terms of the biological rhythms of Tbor LA, respectively (both, P < 0.05) while mice were kept under conditions of a light/dark cycle (12 h:12 h). We also observed a transient, ∼0.3 h shortening of the period of circadian Tbrhythms in mice kept under conditions of constant darkness ( P < 0.01). Interestingly, the observed duration of abnormal circadian rhythms in GF2.0 mice lasted between 1 and 3 wk after the onset of GF ingestion; this finding correlated well with the extent of impairment of heme biosynthesis. When we examined the effects of therapeutic agents for acute porphyria, heme, and hypertonic glucose on the pathological status of GF2.0 mice, it was found that the intraperitoneal administration of heme (10 mg·kg−1·day−1) or glucose (9 g·kg−1·day−1) for 7 days partially reversed (50%) increases in urinary δ-aminolevulinic acids levels associated with acute porphyria. Treatment with heme, but not with glucose, suppressed the phase advance (-like phenomenon) in the diurnal rhythms ( P < 0.05) and restored the decrease of heme ( P < 0.01) in GF2.0 mice. These results suggest that impairments of heme biosynthesis, in particular a decrease in heme, may affect phase and period of circadian rhythms in animals.
Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport
Authors: Daly Kristian , Al-Rammahi Miran , Arora Daleep K. , Moran Andrew W. , Proudman Christopher J. , Ninomiya Yuzo , Shirazi-Beechey Soraya P.
Published: May 2012

The heteromeric sweet taste receptor T1R2-T1R3 is expressed on the luminal membrane of certain populations of enteroendocrine cells. Sensing of sugars and other sweet compounds by this receptor activates a pathway in enteroendocrine cells, resulting in secretion of a number of gut hormones, including glucagon-like peptide 2 (GLP-2). This subsequently leads to upregulation in the expression of intestinal Na+/glucose cotransporter, SGLT1, and increased intestinal glucose absorption. On the basis of the current information available on the horse genome sequence, it has been proposed that the gene for T1R2 ( Tas1R2) is absent in the horse. We show here, however, that horses express both the mRNA and protein for T1R2. Equine T1R2 is most closely homologous to that in the pig and the cow. T1R2 protein, along with T1R3, α-gustducin, and GLP-2 proteins are coexpressed in equine intestinal endocrine cells. Intravenous administration of GLP-2, in rats and pigs, leads to an increase in the expression of SGLT1 in absorptive enterocytes and enhancement in blood glucose concentrations. GLP-2 receptor is expressed in enteric neurons, excluding the direct effect of GLP-2 on enterocytes. However, electric stimulation of enteric neurons generates a neural response leading to SGLT1 upregulation, suggesting that sugar in the intestine activates a reflex increase in the functional expression of SGLT1. Horses possess the ability to upregulate SGLT1 expression in response to increased dietary carbohydrates, and to enhance the capacity of the gut to absorb glucose. The gut sweet receptor provides an accessible target for manipulating the equine gut to absorb glucose (and water), allowing greater energy uptake and hydration for hard-working horses.
Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial V̇o2 during exercise
Authors: Boushel Robert , Fuentes Teresa , Hellsten Ylva , Saltin Bengt
Published: May 2012

Nitric oxide (NO) and prostaglandins (PG) together play a role in regulating blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome- c oxidase. Indomethacin uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus, inhibition of NO and PG synthesis may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG synthesis blockade (l-NMMA and indomethacin, respectively) on mitochondrial respiration in human muscle following knee extension exercise (KEE). Specifically, this study examined the physiological effect of NO, and the pharmacological effect of indomethacin, on muscle mitochondrial function. Consistent with their mechanism of action, we hypothesized that inhibition of nitric oxide synthase (NOS) and PG synthesis would have opposite effects on muscle mitochondrial respiration. Mitochondrial respiration was measured ex vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KEE in control (CON; n = 8), arterial infusion of NG-monomethyl-l-arginine (l-NMMA; n = 4) and Indo ( n = 4) followed by combined inhibition of NOS and PG synthesis (l-NMMA + Indo, n = 8). ADP-stimulated state 3 respiration (OXPHOS) with substrates for complex I (glutamate, malate) was reduced 50% by Indo. State 3 O2 flux with complex I and II substrates was reduced less with both Indo (20%) and l-NMMA + Indo (15%) compared with CON. The results indicate that indomethacin reduces state 3 mitochondrial respiration primarily at complex I of the respiratory chain, while blockade of NOS by l-NMMA counteracts the inhibition by Indo. This effect on muscle mitochondria, in concert with a reduction of blood flow accounts for in vivo changes in muscle O2 consumption during combined blockade of NOS and PG synthesis.
Attenuated glomerular arginine transport prevents hyperfiltration and induces HIF-1α in the pregnant uremic rat
Authors: Schwartz Idit F. , Grupper Ayelet , Soetendorp Hila , Hillel Oren , Laron Ido , Chernichovski Tamara , Ingbir Merav , Shtabski Allexander , Weinstein Talia , Chernin Gil , Shashar Moshe , Hershkoviz Rami , Schwartz Doron
Published: May 2012

Pregnancy worsens renal function in females with chronic renal failure (CRF) through an unknown mechanism. Reduced nitric oxide (NO) generation induces renal injury. Arginine transport by cationic amino acid transporter-1 (CAT-1), which governs endothelial NO generation, is reduced in both renal failure and pregnancy. We hypothesize that attenuated maternal glomerular arginine transport promotes renal damage in CRF pregnant rats. In uremic rats, pregnancy induced a significant decrease in glomerular arginine transport and cGMP generation (a measure of NO production) compared with CRF or pregnancy alone and these effects were prevented by l-arginine. While CAT-1 abundance was unchanged in all experimental groups, protein kinase C (PKC)-α, phosphorylated PKC-α (CAT-1 inhibitor), and phosphorylated CAT-1 were significantly augmented in CRF, pregnant, and pregnant CRF animals; phenomena that were prevented by coadministrating l-arginine. α-Tocopherol (PKC inhibitor) significantly increased arginine transport in both pregnant and CRF pregnant rats, effects that were attenuated by ex vivo incubation of glomeruli with PMA (a PKC stimulant). Renal histology revealed no differences between all experimental groups. Inulin and p-aminohippurate clearances failed to augment and renal cortical expression of hypoxia inducible factor-1α (HIF-1α) significantly increased in CRF pregnant rat, findings that were prevented by arginine. These studies suggest that in CRF rats, pregnancy induces a profound decrease in glomerular arginine transport, through posttranslational regulation of CAT-1 by PKC-α, resulting in attenuated NO generation. These events provoke renal damage manifested by upregulation of renal HIF-1α and loss of the ability to increase glomerular filtration rate during gestation.
Restoration of descending inputs fails to rescue activity following deafferentation of a motor network
Authors: Nahar Jebun , Lett Kawasi M. , Schulz David J.
Published: May 2012

Motor networks such as the pyloric network of the stomatogastric ganglion often require descending neuromodulatory inputs to initiate, regulate, and modulate their activity and their synaptic connectivity to manifest physiologically appropriate output. Prolonged removal of these descending inputs often results in a compensatory response that alters the inputs themselves, their targets, or both. Using the pyloric network of the crab, Cancer borealis, we investigated whether isolation of motor networks would result in alterations that change the responses of these networks to restored modulatory input. We used a reversible block with isotonic sucrose to transiently alter descending inputs into the pyloric network of the crab stomatogastric ganglion. Using this method, we found that blocking neuromodulatory inputs caused a reduced ability for subsequently restored modulatory projections to appropriately generate network output. Our results suggest that this could be due to changes in activity of descending projection neurons as well as changes in sensitivity to neuromodulators of the target neurons that develop over the time course of the blockade. These findings suggest that although homeostatic plasticity may play a critical role in recovery of functional output in a deafferented motor network, the results of these compensatory changes may alter the network such that restored inputs no longer function appropriately.
Regional Cell Proliferation in Microdissected Human Prostate Specimens after Heavy Water Labeling In Vivo: Correlation with Prostate Epithelial Cells Isolated from Seminal Fluid
Authors: Hayes Gregory M. , Simko Jeff , Holochwost Daniel , Kuchinsky Kyle , Busch Robert , Misell Lisa , Murphy Elizabeth J. , Carroll Peter , Chan June , Shinohara Katsuto , Hellerstein Marc K.
Published: May 2012

Purpose: Prostate cancer is detected with increasing frequency but has a highly variable natural history and prognosis and active surveillance of men with low-risk prostate cancer would benefit greatly from minimally invasive methods to identify progression. We describe here two novel in vivo metrics of cell proliferation in men with prostate neoplasia.

Experimental Design: Three groups of men drank heavy water, a nonradioactive, stable isotopic tracer for 14 to 28 days: (i) healthy men, (ii) men scheduled for transrectal core needle biopsy, and (iii) men scheduled for radical prostatectomy. Prostate epithelial cells (PEC) were isolated from ejaculated seminal fluid in all subjects. Histologically graded lesions were microdissected from tissue slides obtained from subjects undergoing surgery and proliferation rates were measured from isolated cells via mass spectrometry.

Results: Proliferation rates of seminal PEC in healthy men (0.10%–0.27%/d) were stable on repeat sampling. Rates above 0.34%/d were seen only in patients with cancer where rates increased progressively from normal tissue through benign prostate hyperplasia, prostate intraepithelial neoplasia, and tumor grades III and IV in all subjects. Seminal PEC kinetics correlated highly with the most proliferative microdissected region in each subject (r2 = 0.94).

Conclusions: Prostate cell proliferation can be measured in vivo from microdissected histopathology sections or noninvasively from seminal fluid where the latter reflects the most proliferative region of the gland. This approach may allow monitoring of progression in men with low-risk prostate cancer. Clin Cancer Res; 18(12); 3250–60. ©2012 AACR.
ErbB3 Inhibitory Surrobodies Inhibit Tumor Cell Proliferation In Vitro and In Vivo
Authors: Foreman Pamela K. , Gore Medini , Kobel Philip A. , Xu Li , Yee Helena , Hannum Charles , Ho Hoangdung , Wang Sandra M. , Tran Hieu V. , Horowitz Michael , Horowitz Lawrence , Bhatt Ramesh R.
Published: May 2012

ErbB3 is an important regulator of tumorigenesis and is implicated in development of resistance to several currently used oncology drugs. We have identified ErbB3 inhibitors based on a novel biologic scaffold termed a surrobody. Two of these inhibitors appear to work by a previously unrecognized mechanism of action. As a consequence, they not only inhibited cell proliferation and intracellular signaling driven by stimulation with the ErbB3 ligand neuregulin (NRG), but also inhibited signaling and proliferation that was driven by overexpression of ErbB2 in the absence of ligand stimulation. In addition, the surrobodies inhibited tumor growth in vivo in both ErbB2-overexpressing and nonoverexpressing cells. In ErbB2-overexpressing cells, both of the anti-ErbB3 surrobodies significantly augmented the activities of trastuzumab, lapatinib, and GDC-0941, agents that inhibit cell proliferation by different mechanisms. Moreover, although NRG diminished the efficacy of these agents, when they were combined with anti-ErbB3 surrobodies the affect of NRG was abrogated. In this capacity, the anti-ErbB3 surrobodies were more effective than the ErbB2/ErbB3 dimerization inhibitory antibody pertuzumab. Despite the fact that these surrobodies appear to engage ErbB3 differently than previously described anti-ErbB3 antibodies, they retain all of the beneficial characteristics of this class of agents, including the ability to augment drugs that inhibit EGF receptor. These anti-ErbB3 agents, therefore, show substantial promise for development as single agents or in combination with other ErbB-directed antibodies or small molecules and may provide for a broader range of therapeutic indications than previously described anti-ErbB3 antibodies. Mol Cancer Ther; 11(7); 1411–20. ©2012 AACR.
A Study of Prostaglandin Pathway Genes and Interactions with Current Nonsteroidal Anti-inflammatory Drug Use in Colorectal Adenoma
Authors: Edwards Todd L. , Shrubsole Martha J. , Cai Qiuyin , Li Guoliang , Dai Qi , Rex Douglas K. , Ulbright Thomas M. , Fu Zhenming , Murff Harvey J. , Smalley Walter , Ness Reid , Zheng Wei
Published: May 2012

Colorectal cancer (CRC) is the second leading cause of cancer-related death and usually arises from colorectal polyps. Screening and removal of polyps reduce mortality from CRC. Colorectal polyps are known to aggregate in families; however the genetic determinants for risk of polyps are unknown. In addition, it has been shown that nonsteroidal anti-inflammatory drug (NSAID) use decreases the risk of CRC and the incidence and size of polyps. In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee–Indiana Adenoma Recurrence Study to evaluate selected genes from the prostaglandin (PG) metabolism and signaling pathways for association with risk of polyps and for interactions with NSAIDs. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian polyp cases and 3,285 Caucasian controls. We carried out multivariable logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. We detected association signals in the genes PGE receptor 3 (PTGER3) and 15-hydroxyprostaglandin dehydrogenase (HPGD), both strong biologic candidates for influence on polyp risk. We did not observe the previously reported effects and effect modification in PG–endoperoxide synthase 2 (PTGS2), PGE receptor 2 (PTGER2), or PGE receptor 4 (PTGER4), although we did observe a single nucleotide polymorphism in PTGER2 associated with risk of multiple adenomas. We also observed effect modification of the HPGD signal by NSAID exposure. Cancer Prev Res; 5(6); 855–63. ©2012 AACR.
Synergism of Staphylococcus aureus Colonization and Allergic Reaction in the Nasal Cavity in Mice
Authors: Hohchi Nobusuke , Hashida Koichi , Ohkubo Jun-ichi , Wakasugi Tetsuro , Mori Takanori , Nguyen Khac-Hung , Kuroda Etsushi , Ikeno Takako , Taniguchi Hatsumi , Suzuki Hideaki
Published: May 2012

Background: The aim of this study is to investigate the reciprocal effect of Staphylococcus aureus colonization and allergic rhinitis in an allergy model of mice. Methods: BALB/c mice with intraperitoneal ovalbumin (OVA) sensitization and/or intranasal S. aureus inoculation were prepared. The following 4 groups were designed: an OVA-sensitized S. aureus-inoculated (AR-SA) group, an OVA-sensitized uninoculated (AR) group, a nonsensitized S. aureus-inoculated (SA) group, and a nonsensitized uninoculated (control) group. After intranasal OVA challenge, nasal lavage fluid, peripheral blood, and nasal mucosa were collected. Polymorphonuclear cells in the nasal lavage fluid were counted, serum OVA-specific IgE and IgG1 were measured by enzyme immunoassays, and IL-4, IL-5, and IFN-γ mRNAs in the nasal mucosa were assessed by quantitative real-time reverse transcription-PCR. The number of S. aureus in the nasal mucosa and lavage fluid was counted. Results: Both eosinophil and neutrophil counts were larger in the AR-SA group than in the other groups. Both IgE and IgG1 levels were higher in the AR and AR-SA groups than in the SA and control groups, and the IgG1 level was higher in the AR-SA group than in the AR group. The expression of IL-4 mRNA was higher in the AR-SA group than in the other groups, and the expression of IL-5 mRNA was higher in the AR-SA group than in the SA group. The AR-SA group showed higher counts of S. aureus in the nasal mucosa than the SA group. Conclusion: These results indicate the mutually potentiating effect of S. aureus colonization and allergic rhinitis.
Paracetamol Hypersensitivity: Clinical Features, Mechanism and Role of Specific IgE
Authors: Rutkowski K. , Nasser S.M. , Ewan P.W.
Published: May 2012

Background: Paracetamol is a common antipyretic/analgesic and a component of many prescription and over- the- counter preparations. Hypersensitivity reactions to paracetamol appear to be increasing, but there are few prevalence data. The mechanism is poorly understood. We identified the clinical features of 32 patients with suspected paracetamol allergy, investigated the underlying mechanism and examined co-existing non-steroidal anti-inflammatory drug (NSAID) tolerance. Methods: A clinical history was taken and skin tests and an oral challenge were performed in 32 patients with suspected paracetamol allergy. Results: Patients presented with a combination of urticaria, angio-oedema (face, hands), erythema (cutaneous features in 94%), dyspnoea (including laryngeal oedema), rhinoconjunctivitis, cough, abdominal pain and anaphylaxis. Two patients had a positive skin prick test (SPT) and unequivocal history of acute urticaria/facial angio-oedema/conjunctivitis/cough after paracetamol with no other triggers. One patient had a positive intradermal test. Oral challenge was positive in 15 of 31 patients (including self-challenge in 4), triggering (a combination of) rhinitis, conjunctivitis, pruritus, erythema, urticaria, angio-oedema, dyspnoea and abdominal pain. Sensitivity was evident in 1 patient on the basis of the patient’s history. Overall, paracetamol hypersensitivity was confirmed in 16 of the 32 patients (50%). Twelve of the 16 paracetamol-allergic patients (75%) tolerated NSAIDs (negative challenge in 6, negative history in 6). Four of these 16 patients (25%) were intolerant of NSAIDs (positive challenge in 1, self-challenge in 3). Conclusions: In past reports on paracetamol hypersensitivity, only single cases of a positive SPT and detectable specific IgE have been described. Our data confirm that specific IgE may be a mechanism underlying paracetamol hypersensitivity, as in this series 18.8% of the patients had specific IgE. In 81.2% of patients, negative skin tests did not exclude paracetamol hypersensitivity, suggesting that it may be mediated by leukotrienes. However, three quarters of our patients tolerated NSAIDs, implicating an alternative mechanism. In patients with suspected paracetamol allergy, skin tests should be performed in addition to clinical history and oral challenge.
Differential Expression of Toll-Like Receptor 2 on Dendritic Cells from Asymptomatic and Symptomatic Atopic Donors
Authors: von Bubnoff D. , Sell U. , Arriens S. , Specht S. , Hoerauf A. , Bieber T.
Published: May 2012

Background: Early microbial exposure may reduce the risk for developing allergies on an atopic genetic background. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns of microbes and modulate innate and adaptive immunity. Different expression of TLRs in symptomatic and asymptomatic atopic donors may contribute to the development of allergic disease. Methods: Monocytes and monocyte-derived dendritic cells (DCs) from symptomatic (n = 12) and asymptomatic atopic donors (n = 11), healthy nonatopics (n = 14) and from patients with psoriasis (n = 13) were analyzed for their expression of TLR2, TLR4 and TLR9 by real-time PCR. Results: Monocytes did not show any differences in TLR2, TLR4 and TLR9 expression between the 4 groups. In contrast, DCs from asymptomatic donors showed an enhanced expression of TLR2 over DCs from nonatopics (p = 0.038) and just failed to reach significance when compared to symptomatic atopic patients (p = 0.060). TLR2 expression kinetics from monocytes to monocyte-derived DCs showed sustained expression of TLR2 in DCs only from asymptomatic donors but downregulation in the other groups. In DCs from symptomatic atopic donors, the expression of TLR2 correlated significantly with total IgE values in the serum (p = 0.01994). Conclusion: Differential expression and functional regulation of TLR2 expression by DCs from symptomatic and asymptomatic atopic donors may be important for the manifestation of allergic disease. Increased and sustained TLR2 expression on DCs, possibly as a result of an increased exposure to microorganisms or as a mechanism enhancing the sensitivity of microbe detection, may be of functional importance for the maintenance of clinical unresponsiveness toward allergens.
Respiratory Syncytial Virus Persistence in Macrophages Downregulates Intercellular Adhesion Molecule-1 Expression and Reduces Adhesion of Non-Typeable Haemophilus influenzae
Authors: Arrevillaga Gerardo , Gaona Jorge , Sánchez Carla , Rosales Víctor , Gómez Beatríz
Published: May 2012

Background: Persistence of respiratory syncytial virus (RSV) has been associated with episodes of chronic obstructive pulmonary disease (COPD); furthermore, co-infection of RSV with non-typeable Haemophilus influenzae (NTHi) is increasingly recognized as a cause of exacerbations of COPD. Objective: To study whether RSV persistence in a macrophage (Mφ)-like cell line alters NTHi uptake (adhesion and ingestion). Methods: A murine Mφ-like cell line persistently infected with RSV (MφP) was used. The effects of RSV persistence on NTHi uptake by MφP and mock-infected Mφ (MφN) were determined by flow-cytometric assays with NTHi labelled with either ethidium bromide or FITC. Expression of intercellular adhesion molecule-1 (ICAM-1), a ligand for NTHi, was determined by measuring mRNA through real-time PCR and protein by Western blot assays. Results: RSV persistence reduced both the capacity of Mφ to take up bacteria and the expression of ICAM-1 mRNA and protein. Furthermore, when ICAM-1 was blocked with anti-ICAM-1 antibody, the adhesion capacity of NTHi was significantly reduced for MφN, whereas for MφP the effect was less evident, implying that ICAM-1 participates in NTHi adhesion to Mφ. Conclusion: RSV persistence in murine Mφ diminishes their capacity to adhere and ingest NTHi through downregulation of ICAM-1 expression at the transcriptional level.
Influence of Minimal Changes in Preoperative Renal Function on Outcomes of Cardiac Surgery
Authors: Shavit Linda , Tauber Rachel , Lifschitz Meyer , Bitran Daniel , Slotki Itzchak , Fink Daniel
Published: May 2012

Background/Aims: Cardiovascular morbidity and mortality are high in patients with chronic kidney disease. We evaluated the influence of small differences in preoperative kidney function on mortality and complications following cardiac surgery. Methods: This is an observational study that included adult patients undergoing cardiac surgery. Preoperative estimated glomerular filtration rate (eGFR) was estimated by the 4-component Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on preoperative creatinine levels. For analysis, patients were divided into groups according to their preoperative creatinine (0.2 mg/dl increments) and eGFR levels (15–30 ml/min/1.73 m2 decrements). Results: Data on 5,340 patients were analyzed. A significant increase in postoperative mortality was demonstrated with preoperative creatinine at high-normal versus low-normal values (OR 1.7, 95% CI: 1–2.5; p = 0.02). For preoperative creatinine >1.2 mg/dl, adjusted OR for in-hospital mortality increased stepwise with every 0.2-mg/dl increment of creatinine. In addition, a statistically significant increment of mortality was detected with every 15-ml/min/1.73 m2 decrement in preoperative eGFR. Conclusions: Minimal changes of preoperative kidney function are associated with a substantial increase in the risk of mortality and morbidity following cardiac surgery. Even within the ‘normal’ range, minimal increases in serum creatinine levels are associated with increased risk of adverse events postoperatively.
Early Recovery of Immunity after Cord-Blood Transplantation in Children: Qualitative Features and Impact of Cytomegalovirus Infection
Authors: Farnault Laure , Chambost Hervé , Zandotti Christine , Mallet Françoise , Barlogis Vincent , Galambrun Claire , Michel Gerard , Olive Daniel
Published: May 2012

This study investigated immune recovery and the effect of cytomegalovirus (CMV) infection on the early stages of T-lymphocyte recovery after cord-blood transplantation (CBT) from unrelated donors to 24 children. In addition, 15 children who were recipients of a bone-marrow transplant (BMT) were studied concomitantly. The main objectives of the study were whether lymphocytes from CBT recipients were capable of rapid qualitative differentiation in the effector memory (EM) stage, of regenerating de novo naïve cells and of responding to CMV infection. Results showed that CB lymphocytes were mainly differentiated into the EM stage at 3 months and into the naïve stage at 6 months. CMV infection induced a dramatic increase in CD8 but not CD4 T-cell counts, and differentiation into the EM stage with high perforin contents. Our data suggest that CB lymphocytes are capable of rapid differentiation in children, but stabilization of lymphocyte counts in children is associated with effective naïve subset regeneration at 6 months. Moreover, the T-cell repertoire is capable of rapid adjustment when CMV infection occurs.
Central Upper Lip Reconstruction by Two Vermillion Flaps and a Rotational Skin Flap
Authors: Vaienti Luca , Zilio Dino , Di Matteo Adriano , Riccio Michele , Marchesi Andrea
Published: May 2012

Background: Lip cancer is the most frequent malignant neoplasm of the oral cavity. Defects larger than one-fourth of total upper lip length require reconstruction by established techniques or multiple procedures. Methods: The patient was a 53-year-old man who presented with a 1.5 cm basal cell carcinoma in the central upper lip. Two opposed vermillion flaps were designed and advanced following radical tumor excision to create a new skin-vermilion border. A rotational skin flap was prepared to maintain the normal aspect of the filter area. Results: The patient was evaluated 1 year after the operation. He showed well-healed flaps with excellent aesthetic and functional results of the filter area and Cupid’s bow. Conclusion: Within certain limits (maximum one-third of total upper lip length), double vermillion opposing flaps with a rotational skin flap appear to be a valid method for upper lip reconstruction.