bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Expression of Apolipoproteins E, J, and A‐I in Alzheimer's Disease
Authors: Harr Steven D. , Uint Luciana , Hollister Richard , Hyman Bradley T. , Mendez Armando J.
Published: July 2010

Abstract: Inheritance of the ε4 allele of apolipoprotein (apo) E is associated with increased risk of Alzheimer's disease (AD) and with increased β‐amyloid peptide (Aβ) deposition in the cortex. Apo E is a member of a family of exchangeable apos, characterized by the presence of amphipathic α‐helical segments that allow these molecules to act as surfactants on the surface of lipoprotein particles. Two members of this family, apo E and apo J, have been shown to bind soluble Aβ, and both are associated with senile plaques in the AD cortex. We now have studied the pattern of brain apo expression and found that five members of this class are present: apo A‐I, A‐IV, D, E, and J. By contrast, apos A‐II, B, and C‐II were not detectable. Immunohistochemistry revealed that, in addition to apo E and apo J, apo A‐I immunostained occasional senile plaques in AD cortex. Immunoblot analysis showed no difference in the relative amounts of any of these apos in tissue homogenates of frontal lobe from AD or control patients. Comparison by APO E genotype showed no differences in the amount of apo E in brain among APO E ε3/3, ε3/4, or ε4/4 individuals; however, a significant decrease in the amount of apo J was associated with the APO E ε4 allele. No differences in apo J levels were detected in CSF samples of AD subjects. We propose that several members of the exchangeable apo family may interact with Aβ deposits in senile plaques through common amphipathic α‐helical domains. Competition among these molecules for binding of Aβ or Aβ aggregates may influence the deposition of Aβ in senile plaques.
A One‐Dimensional (Proton and Phosphorus) and Two‐Dimensional (Proton) In Vivo NMR Spectroscopic Study of Reversible Global Cerebral Ischemia
Authors: Brulatout S. , Méric Ph. , Loubinoux I. , Borredon J. , Corrèze J. L. , Roucher P. , Gillet B. , Bérenger G. , Beloeil J. C. , Tiffon B. , Mispelter J. , Seylaz J.
Published: July 2010

Abstract: The suitability of two‐dimensional (2D) proton spectroscopy for monitoring, in vivo, the changes in levels of brain metabolites induced by cerebral ischemia was investigated in an experimental model of 30‐min reversible ischemia induced by four‐vessel occlusion in the rat. The resulting data were compared with those obtained by one‐dimensional (1D) proton and phosphorus spectroscopy. Phosphorus spectra obtained during ischemia showed significant drops in levels of phosphocreatine (−73%), β‐ATP (−60%), and intracellular pH (to 6.30) and an increase in inorganic phosphate level (905%). 1D and 2D proton spectra showed decreases in the N‐acetylaspartate/creatine‐phosphocreatine ratio that were not significantly different [−21% (1D) and −32% (2D)]. Similarly, the increases in lactate/creatine‐phosphocreatine ratio were not significantly different [2,546% (1D) and 3,020% (2D)]. 2D spectroscopy also indicated a decrease in aspartate (−66%) and an increase in the inositol‐choline derivative (+124%) pools during ischemia and an increase in alanine pool (+516%) during reperfusion. The glutamate‐glutamine pool and taurine content did not change significantly during ischemia but decreased during reperfusion. The glucose level transiently decreased (−67%) during ischemia and increased immediately after (+261%). The levels of all the metabolites investigated returned to control values within 175 min after ischemia. 2D spectroscopy seems to be a reliable method of monitoring the changes in levels of cerebral compounds known to be involved in ischemia.
Induction of Urokinase‐Type Plasminogen Activator in Rat Facial Nucleus by Axotomy of the Facial Nerve
Authors: Nakajima Kazuyuki , Reddington Martin , Kohsaka Shinichi , Kreutzberg Georg W.
Published: July 2010

Abstract: The response of plasminogen activator activity in the CNS to peripheral nerve axotomy was examined in vivo. After transection of the rat facial nerve, a transient increase in plasminogen activator activity was observed in the facial nucleus on the operated side with maximal activity 3–5 days after lesion. This activity was inhibited by the urokinase‐specific inhibitor amiloride but not by antibodies against tissue plasminogen activator. The molecular mass of the induced form of plasminogen activator was estimated to be ∼48 kDa. An in vitro assay of plasminogen hydrolysis also demonstrated an increase in amiloride‐sensitive plasminogen activator activity in facial nerve extracts following facial nerve axotomy. These data indicate that the plasminogen activator activity induced in the facial nucleus following axotomy of facial motoneurons is of the urokinase type. It is suggested that the urokinase‐type plasminogen activator might play a role in the events accompanying injury and regeneration in the facial nucleus following motoneuron lesion.
Binding of 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase to Myelin: An In Vitro Study
Authors: De Angelis Dino A. , Braun Peter E.
Published: July 2010

Abstract: The binding of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase isoform 1 (CNP1) to myelin and its association with cytoskeletal elements of the sheath have been characterized with in vitro synthesized polypeptides and purified myelin. We have previously shown that the cysteine residue present in the carboxy‐terminal CXXX box of CNP1 is isoprenylated, and that both C15 farnesyl and C20 geranylgeranyl isoprenoids can serve as substrates for the modification. Here, we have mutated the CXXX box to obtain selectively farnesylated CNP1 or geranyl‐geranylated CNP1 and found that these two modified forms of CNP1 behave identically in all of the assays performed. Isoprenylation is essential but not sufficient for the binding of in vitro synthesized CNP1 to purified myelin, because a control nonmyelin protein is isoprenylated, yet unable to bind to myelin. In our assay, membrane‐bound CNP1 partitions quantitatively into the non‐ionic detergent‐insoluble phase of myelin, suggesting that CNP1 binds to cytoskeletal elements within myelin. However, isoprenylated CNP1 fails to bind to the cytoskeletal matrix isolated from myelin by detergent treatment, implying that both detergent‐soluble and insoluble myelin components are involved in the binding of CNP1. A model for the interactions between CNP1 and myelin is presented, consistent with models proposed for other isoprenylated proteins.
Modulation of 45Ca2+ Influx into Cells Stably Expressing Recombinant Human NMDA Receptors by Ligands Acting at Distinct Recognition Sites
Authors: Grimwood Sarah , Gilbert Elizabeth , Ragan C. Ian , Hutson Peter H.
Published: July 2010

Abstract: A 45Ca2+ influx assay has been used to investigate the pharmacology of stably expressed recombinant human NR1a/NR2A and NR1a/NR2B N‐methyl‐d‐aspartate (NMDA) receptors. Inhibition of glutamate‐stimulated 45Ca2+ influx by six glycine‐site antagonists and inhibition of glycine‐stimulated 45Ca2+ influx by five glutamate‐site antagonists revealed no significant differences between affinity values obtained for NR1a/NR2A and NR1a/NR2B receptors. The polyamine site agonist spermine showed differential modulation of glutamate‐ and glycine‐stimulated 45Ca2+ influx for recombinant NMDA receptors, inhibiting and stimulating 45Ca2+ influx into cells expressing NR1a/NR2A receptors (IC50 = 408 µM) and NR1a/NR2B receptors (EC50 = 37.3 µM), respectively. The antagonist ifenprodil was selective for NR1a/NR2B receptors (IC50 = 0.099 µM) compared with NR1a/NR2A receptors (IC50 = 164 µM). The effects of putative polyamine site antagonists, redox agents, ethanol, and Mg2+ and Zn2+ ions were also compared between NR1a/NR2A and NR1a/NR2B receptors. This study demonstrates the use of 45Ca2+ influx as a method for investigating the pharmacology of the numerous modulatory sites that regulate the function of recombinant human NMDA receptors stably expressed in L(tk‐) cells.
Chronic In Vivo Sodium Azide Infusion Induces Selective and Stable Inhibition of Cytochrome c Oxidase
Authors: Bennett M. Catherine , Mlady Gary W. , Kwon Young‐Hwa , Rose Gregory M.
Published: July 2010

Abstract: The effect of chronic subcutaneous infusion of sodium azide on the activity of mitochondrial respiratory chain enzymes was investigated in Sprague‐Dawley rats. Treatment with ∼1 mg/kg/h sodium azide induced chronic, partial inhibition of cytochrome c oxidase, whereas the activities of respiratory complexes I and III were not significantly affected. The inhibition of cytochrome c oxidase was evident by 7 days after infusion began, and the effect was stable for at least 3 weeks. The selectivity of azide for cytochrome c oxidase is discussed in the context of other findings of azide effects on enzymes. The results of the present study indicate that the sodium azide infusion paradigm described here provides a useful tool for the evaluation of selective and stable cytochrome oxidase inhibition in vivo.
The Roles of CRE, TRE, and TRE‐Adjacent S1 Nuclease Sensitive Element in the Regulation of Tyrosine Hydroxylase Gene Promoter Activity by Angiotensin II
Authors: Kim Ella L. , Esparza Frederico M. , Stachowiak Michal K.
Published: July 2010

Abstract: The cis elements mediating activation of the tyrosine hydroxylase gene by angiotensin II were examined by transfecting tyrosine hydroxylase promoter‐luciferase constructs into cultured bovine adrenal medullary cells. Angiotensin II‐responsive elements are located within −54/+25‐bp and −269/−55‐bp promoter regions and were identified, respectively, as cyclic AMP (CRE)‐ and 12‐O‐tetradecanoylphorbol 13‐acetate responsive element (TRE)‐like sequences. Unlike CRE, TRE also supports basal promoter activity. Mutations of TRE or CRE that reduced angiotensin II stimulation abolished in vitro binding of nuclear proteins to those elements, suggesting that proteins forming CRE‐ and TRE‐inducible complexes may mediate angiotensin II stimulation. The TRE is adjacent to a dyad symmetry element. Those two sites form a common regulatory unit in which the dyad symmetry element acts as a repressor of the TRE site. Isolated dyad symmetry element did not bind nuclear proteins in vitro. In supercoiled DNA it exhibited S1 nuclease sensitivity and was recognized by a DNA cruciform‐specific antibody consistent with the extrusion of a cruciform structure that overlaps with the TRE. A mutation that abolished formation of the cruciform correlated with a loss of repressor activity. We propose a novel model of tyrosine hydroxylase gene regulation in which functions of the TRE are modulated via structural transition in the adjacent DNA.
Similarity Between Rat Brain Nicotinic α‐Bungarotoxin Receptors and Stably Expressed α‐Bungarotoxin Binding Sites
Authors: Quik M. , Choremis J. , Komourian J. , Lukas R. J. , Puchacz E.
Published: July 2010

Abstract: The present results demonstrate stable expression of α‐bungarotoxin (α‐BGT) binding sites by cells of the GH4C1 rat pituitary clonal line. Wild‐type GH4C1 cells do not express α‐BGT binding sites, nor do they contain detectable mRNA for nicotinic receptor α2, α3, α4, α5, α7, β2, or β3 subunits. However, GH4C1 cells stably transfected with rat nicotinic receptor α7 cDNA (α7/GH4C1 cells) express the transgene abundantly as mRNA, and northern analysis showed that the message is of the predicted size. The α7/GH4C1 cells also express saturable, high‐affinity binding sites for 125I‐labeled α‐BGT, with a KD of 0.4 nM and Bmax of 3.2 fmol/106 intact cells. 125I‐α‐BGT binding affinities and pharmacological profiles are not significantly different for sites in membranes prepared either from rat brain or α7/GH4C1 cells. Furthermore, KD and Ki values for 125I‐α‐BGT binding sites on intact α7/GH4C1 cells are essentially similar to those for hippocampal neurons in culture. Sucrose density gradient analysis showed that the size of the α‐BGT binding sites expressed in α7/GH4C1 cells was similar to that of the native brain α‐BGT receptor. Chronic exposure of α7/GH4C1 cells in culture to nicotine or an elevated extracellular potassium concentration induces changes in the number of α‐BGT binding sites comparable to those observed in cultured neurons. Collectively, the present results show that the properties of α‐BGT binding sites in transfected α7/GH4C1 cells resemble those for brain nicotinic α‐BGT receptors. If the heterologously expressed α‐BGT binding sites in the present study are composed solely of α7 subunits, the results could suggest that the rat brain α‐BGT receptor has a similar homooligomeric structure. Alternatively, if α‐BGT binding sites exist as heterooligomers of α7 plus some other previously identified or novel subunit(s), the data would indicate that the α7 subunits play a major role in determining properties of the α‐BGT receptor.
Clusterin (Apo J) Protects Against In Vitro Amyloid‐β(1–40) Neurotoxicity
Authors: Boggs Leonard N. , Fuson Kimberly S. , Baez Melvyn , Churgay Lisa , McClure Don , Becker Gerald , May Patrick C.
Published: July 2010

Abstract: Clusterin is a secreted glycoprotein that is markedly induced in many disease states and after tissue injury. In the CNS, clusterin expression is elevated in neuropathological conditions such as Alzheimer's disease (AD), where it is found associated with amyloid‐β (Aβ) plaques. Clusterin also coprecipitates with Aβ from CSF, suggesting a physiological interaction with Aβ. Given this interaction with Aβ, the goal of this study was to determine whether clusterin could modulate Aβ neurotoxicity. A mammalian recombinant source of human clusterin was obtained by stable transfection of hamster kidney fibroblasts with pADHC‐9, a full‐length human cDNA clone for clusterin. Recombinant clusterin obtained from this cell line, as well as a commercial source of native clusterin purified from serum, afforded dose‐dependent neuroprotection against Aβ(1–40) when tested in primary rat mixed hippocampal cultures. Clusterin afforded substoichiometric neuroprotection against several lots of Aβ(1–40) but not against H2O2 or kainic acid excitotoxicity. These results suggest that the elevated expression of clusterin found in AD brain may have effects on subsequent amyloid‐β plaque pathology.
Identification of an Octamer‐1 Transcription Factor Binding Site in the Promoter of the Mouse μ‐Opioid Receptor Gene
Authors: Liang Yanbin , Carr Lucinda G.
Published: July 2010

Abstract: In a previous study we showed that a region from −182 to +10 bp in the mouse μ‐opioid receptor (MOR) promoter exhibited strong promoter activity. To identify protein‐DNA interactions in this fragment, gel shift and DNase I footprint analyses were performed using nuclear extracts from mouse brain and the human neuroblastoma cell line, SK‐N‐SH. Two regions, nucleotide (nt) −121 to −100 and nt −42 to −22, were identified as being specific protein binding sites. The protein‐DNA interaction in the nt −42 to −22 region was characterized in detail in this study. Methylation interference analysis of this region showed that nuclear protein from SK‐N‐SH cells contacted nucleotides within the sequence ATG‐CAAAT, which is a binding motif for octamer trans‐acting factors. An octamer‐1 (Oct‐1)‐specific antibody supershifted the protein‐DNA complex in a gel shift assay. A UV cross‐linking experiment showed that a nuclear protein, whose molecular weight is similar to that of the Oct‐1 factor, bound to the octamer element in the nt −42 to −22 region. Mutagenesis of four base pairs within the octamer cis‐acting element eliminated the specific protein binding in vitro. When the MOR‐luciferase reporter construct (−182 to +10 bp) with the same four base pairs mutated was transiently transfected into SK‐N‐SH cells, a 200% increase in transcriptional activity was observed. Collectively, these data suggest that Oct‐1 is binding to the octamer motif in the MOR gene and negatively modulating MOR gene expression.
The Lck Tyrosine Kinase Is Expressed in Brain Neurons
Authors: Omri Boubaker , Crisanti Patricia , Marty Marie‐Chantal , Alliot Françoise , Fagard Rémy , Molina Thierry , Pessac Bernard
Published: July 2010

Abstract: The lck gene product, p56lck, is a member of the src‐related family of protein tyrosine kinases. It is known as lymphocyte specific and involved in thymocyte development and in the immune response mediated by the T cell receptor. We report that the lck gene is also expressed in adult mouse CNS and that brain p56lck is similar to the thymus protein. In situ hybridization and immunohistochemistry show that the lck gene is expressed in neurons throughout the brain in distinct regions, including hippocampus and cerebellum. In primary cultures from fetal mouse brain, neuronal cells are immunoreactive to Lck antiserum. This suggests that the lck gene product might be involved in a new signal transduction pathway in mouse brain.
Glutathione Content as an Indicator for the Presence of Metabolic Pathways of Amino Acids in Astroglial Cultures
Authors: Dringen Ralf , Hamprecht Bernd
Published: July 2010

Abstract: The intracellular content of glutathione in astroglia‐rich primary cultures derived from the brains of newborn rats was measured to be 32.1 ± 5.4 nmol/mg of protein. During a 24‐h incubation in a minimal medium lacking amino acids and glucose, the content of glutathione in these cultures was reduced to 52% of the original content. On refeeding of glucose, glutamate, glycine, and cysteine, glutathione was resynthesized. A maximal content of glutathione was found 4 h after refeeding, exceeding the amount of glutathione of untreated cultures by 72%. Maximal glutathione synthesis was observed only if glutamate, cysteine, and glycine were present. If successively each one of these amino acids was made limiting for the synthesis of glutathione, half‐maximal contents of glutathione were found at 0.2 mM glutamate, 20 µM cysteine, or 10 µM glycine. Replacement of glutamate or glycine by other amino acids revealed the potential of astroglial cells to convert glutamine, aspartate, asparagine, proline, and ornithine into glutamate, and serine into glycine. These results demonstrate that the concentration of intracellular glutathione can serve as an indicator for the presence of metabolic pathways of amino acids in cultured cells.
Guanine Nucleotide Regulatory Proteins, Gq and Gi1/2, Mediate Platelet‐Activating Factor‐Stimulated Phosphoinositide Metabolism in Immortalized Hippocampal Cells
Authors: Shi Leng‐Chu , Wang Hoau‐Yan , Horwitz Joel , Friedman Eitan
Published: July 2010

Abstract: Platelet‐activating factor (PAF) may be a neuromodulator involved in neural cell differentiation, cerebral inflammation, and ischemia. The PAF receptor is a member of the G protein‐coupled receptor superfamily. In the present study, we sought to define the specific G protein(s) that mediate PAF‐stimulated phosphoinositide (PI) metabolism in an immortalized hippocampal cell line, HN33.11. PAF increased the production of 3H‐labeled inositol phosphates (IPs) with EC50 values of 1.2–1.5 nM. The effect of PAF on 3H‐IPs formation was completely blocked by the PAF antagonist BN 50739 at a concentration of 300 nM. Pertussis toxin pretreatment attenuated PAF‐stimulated 3H‐IPs production by 20–30% (p < 0.05). Consistent with a role for Gi1/2 in this response, antiserum against Gαi1/2 blocked the response to a similar degree. Pretreatment of permeabilized cells with Gαq/11 antiserum attenuated the response by 70% (p < 0.05), suggesting a role for Gq/11 in mediating the PAF response in this cell line. Stimulation with PAF increased [α‐32P]‐GTP binding to both Gαq and Gαi1/2 proteins. Moreover, specific [3H]PAF binding sites coprecipitated with Gαq and Gαi1/2 proteins. The results suggest that PAF‐stimulated PI metabolism in HN33.11 cells is mediated by both Gq and Gi1/2 proteins.
Phorbol Esters but Not the Cholinergic Agonists Oxotremorine‐M and Carbachol Increase Release of the Amyloid Precursor Protein in Cultured Rat Cortical Neurons
Authors: Mills Julia , Reiner Peter B.
Published: July 2010

Abstract: Conventional secretory processing of the amyloid precursor protein is nonamyloidogenic, releasing carboxyl‐terminus‐truncated amyloid precursor protein derivatives while cleaving the amyloid β‐peptide within its sequence. Alternative processing routes are potentially amyloidogenic, yielding the amyloid β‐peptide segment intact. In continuous cell lines, secretory processing of the amyloid precursor protein is regulated by both protein kinase C and muscarinic receptor stimulation. However, the first and second messenger systems that regulate amyloid precursor protein release in central neurons are still under investigation. In the present investigation, we examined whether or not first and second messengers of cholinergic neurotransmission increase production of soluble derivatives of the amyloid precursor protein in primary cultures of rat cortical neurons. Activation of protein kinase C by the phorbol esters phorbol 12,13‐dibutyrate and phorbol 12‐myristate 13‐acetate increased production of the soluble form of the amyloid precursor protein dramatically. In contrast, activation of muscarinic receptors by oxotremorine‐M or carbachol did not result in a significant increase in amyloid precursor protein release. Similarly, chemically induced depolarization using 35 mM KCI did not alter production of soluble amyloid precursor protein derivatives. Our data suggest that although protein kinase C stimulation plays an important role in regulating release of the amyloid precursor protein, cholinergic neurotransmission does not regulate its release in cultured rat cortical neurons.
Cyclothiazide Unmasks an AMPA‐Evoked Release of Arachidonic Acid from Cultured Striatal Neurones
Authors: Williams Robert J. , Glowinski Jacques
Published: July 2010

Abstract: The joint, but not independent, activation of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) and metabotropic glutamate receptors induces liberation of arachidonic acid from cultured mouse striatal neurones. We examined whether blocking AMPA receptor desensitisation with cyclothiazide would modify this response. Cyclothiazide strongly potentiated the combined AMPA/(1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (ACPD)‐evoked release of arachidonic acid (EC50 of ∼7 µM) but did not modulate the basal, ACPD, or NMDA response. The enhanced liberation of arachidonic acid, observed in the presence of cyclothiazide, was due to the appearance of a genuine AMPA response that was independent of an associative activation of metabotropic receptors. The potentiated and nonpotentiated AMPA responses were inhibited by both competitive [2,3‐dihydroxy‐6‐nitro‐7‐sulphamoylbenzo(f)quinoxaline] and 2,3‐benzodiazepine noncompetitive (GYKI 53655 and GYKI 52466) receptor antagonists. Cyclothiazide was equally effective at potentiating the AMPA response in either the presence or absence of glucose, suggesting that the increased glutamate‐evoked arachidonic acid release observed in these cells under conditions of glucose deprivation is not due to reduced AMPA receptor desensitisation. The enhanced liberation of arachidonic acid measured in the presence of cyclothiazide appeared to result from a large (fourfold) elevation of the AMPA‐induced increase in intracellular calcium level. Therefore, an AMPA‐evoked mobilisation of arachidonic acid could potentially contribute to non‐NMDA receptor‐mediated neurotoxicity, which has been observed in neuronal cells in the presence of cyclothiazide.
Differential Axonal Transport of Soluble and Insoluble τ in the Rat Sciatic Nerve
Authors: Tashiro Tomoko , Sun Xiaoyan , Tsuda Morihiro , Komiya Yoshiaki
Published: July 2010

Abstract: Axonal transport of microtubule‐associated protein τ was studied in the motor fibers of the rat sciatic nerve 1–4 weeks after labeling of the spinal cord with [35S]methionine. As 60–70% of low molecular weight τ in this system was found to be insoluble in 1% Triton‐containing buffer, labeled proteins in 6‐mm consecutive nerve segments were first separated into Triton‐soluble and insoluble fractions. Two‐dimensional gel electrophoresis and immunoblotting with anti‐tau antibody confirmed the presence of τ among labeled, transported proteins in both fractions. Isoform composition of labeled τ was similar to that of bulk axonal τ, the most acidic species with apparent molecular mass of 66 kDa being the major component. Transport profiles obtained by measuring radioactivities associated with this major isoform showed that soluble and insoluble τ were transported at different rates. Insoluble τ, which contained the majority of τ‐associated radioactivity, was transported at 1.7 mm/day in slow component a (SCa), whereas soluble τ was transported faster, at 3 mm/day, corresponding to the rate of slow component b (SCb). Cotransport of insoluble τ with insoluble tubulin in SCa suggests its association with stable microtubules.
Catecholamine Phenotyping: Clues to the Diagnosis, Treatment, and Pathophysiology of Neurogenetic Disorders
Authors: Goldstein David S. , Lenders Jacques W. M. , Kaler Stephen G. , Eisenhofer Graeme
Published: July 2010

Abstract: One purpose of clinical neurochemistry has been to indicate “activities” of catecholamine systems, by assaying levels of the effector compounds or their metabolites in body fluids such as plasma, cerebrospinal fluid, urine, or microdialysate. This review discusses a new purpose: relating specific catecholaminergic phenotypes to neurogenetic disorders. Distinctive catecholamine patterns in several neurogenetic conditions reflect enzyme deficiencies as direct or indirect effects of gene mutations. These neurochemical patterns can provide potentially important clues to the diagnosis, treatment, and pathophysiology of neurogenetic disorders. Linking genetic abnormalities with molecular mechanisms and clinical manifestations of disease represents a useful new direction in clinical neurochemistry.
Inhibition of p42 and p44 Mitogen‐Activated Protein Kinase Activity by PD98059 Does Not Suppress Nerve Growth Factor‐Induced Survival of Sympathetic Neurones
Authors: Virdee Kanwar , Tolkovsky Aviva M.
Published: July 2010

Abstract: Nerve growth factor (NGF) induces persistent p42 and p44 mitogen‐activated protein kinase (MAPK) activity in sympathetic neurones in parallel to its survival‐promoting activity. To investigate whether these MAPK activities are necessary for NGF‐induced survival, we have inhibited NGF‐stimulated p42/p44 MAPK activity over extended periods using the compound 2‐(2′‐amino‐3′‐methoxyphenyl)‐oxanaphthalen‐4‐one (PD98059). Despite attaining up to 95% inhibition of p42/p44 MAPK activity in cultures treated with NGF and PD98059, neuronal survival is maintained undiminished, although a decrease in the density of the neuritic network is observed. Because p21Ras activity is essential for NGF‐induced survival, we conclude that p21Ras‐linked activities other than p42 and p44 MAPKs are responsible for mediating NGF‐dependent survival of rat sympathetic neurones.
An expansion of the homoclinic splitting matrix for the rapidly, quasiperiodically, forced pendulum
Authors: Stenlund Mikko
Published: July 2010

We study a Hamiltonian describing a pendulum coupled with several anisochronous oscillators, devising an expansion for the splitting matrix associated with a homoclinic point. This expansion consists of contributions that are manifestly exponentially small in the limit of vanishing hyperbolicity by a shift-of-contour argument. An exponentially small upper bound on the splitting is implied. The focus of this paper is on the method.
Dynamics of a driven surface
Authors: Narasimhan S. L. , Baumgaertner A.
Published: July 2010

We present a Monte Carlo study of an Edwards–Wilkinson type of surface when it is driven by another random surface which drifts with a rate 0<ϕ<1. When it is driven by another drifting surface, it is shown to be of the Kardar–Parisi–Zhang (KPZ) type; we show that the asymptotic drift of its center of mass is preceded by a subdiffusive regime characterized by an effective exponent whose value is slightly less than that of the KPZ growth exponent (β=1/3) because of slow crossover. Our numerical study demonstrates that the growth of fluctuations for the driven surface shows an extremely slow crossover to the KPZ regime observable only for very large system sizes. The equilibrium fluctuation of the surface exhibits a minimum at a certain driving rate ϕ∗, which separates the regimes of entropic repulsion and entropic compliance. Since our model of interacting surfaces is a generalization of the Brownian Ratchet model for protrusions of biological cell membranes, we discuss it vis-a-vis the standard load-velocity relationship, and we compare the present model membrane to cell membranes.
Structural changes of poly(N-isopropylacrylamide)-based microgels induced by hydrostatic pressure and temperature studied by small angle neutron scattering
Authors: Lietor-Santos J. J. , Gasser U. , Vavrin R. , Hu Z. B. , Fernandez-Nieves A.
Published: July 2010

We study the structural properties of microgels made of poly(N-isopropylacrylamide) and acrylic acid as a function of hydrostatic pressure and temperature using small angle neutron scattering. Hydrostatic pressure induces particle deswelling by changing the mixing of the microgel with the solvent, similar to temperature. We extend this analogy to the structural properties of the particles and show that the form factor at a certain temperature is equal to the form factor at a certain hydrostatic pressure. We fit the results with an existent model for the microgel structure and carefully analyze the fitting procedure in order to obtain physically meaningful values of the free parameters in the model.
Tree expansion in time-dependent perturbation theory
Authors: Brouder Christian , Mestre Ângela , Patras Frédéric
Published: July 2010

The computational complexity of time-dependent perturbation theory is well known to be largely combinatorial whatever the chosen expansion method and family of parameters (combinatorial sequences, Goldstone and other Feynman-type diagrams, etc.). We show that a very efficient perturbative expansion, both for theoretical and numerical purposes, can be obtained through an original parametrization by trees and generalized iterated integrals. We emphasize above all the simplicity and naturality of the new approach that links perturbation theory with classical and recent results in enumerative and algebraic combinatorics. These tools are applied to the adiabatic approximation and the effective Hamiltonian. We prove perturbatively and nonperturbatively the convergence of Morita’s generalization of the Gell–Mann and Low wave function. We show that summing all the terms associated with the same tree leads to an utter simplification where the sum is simpler than any of its terms. Finally, we recover the Rayleigh-Schrödinger time-independent equation for the wave operator and we give an explicit nonrecursive expression for the term corresponding to an arbitrary tree.
Maximal violation of Bell inequalities by position measurements
Authors: Kiukas J. , Werner R. F.
Published: July 2010

We show that it is possible to find maximal violations of the Clauser-Horne-Shimony-Holt (CHSH) Bell inequality using only position measurements on a pair of entangled nonrelativistic free particles. The device settings required in the CHSH inequality are done by choosing one of two times at which position is measured. For different assignments of the “+” outcome to positions, namely, to an interval, to a half-line, or to a periodic set, we determine violations of the inequalities and states where they are attained. These results have consequences for the hidden variable theories of Bohm and Nelson, in which the two-time correlations between distant particle trajectories have a joint distribution, and hence cannot violate any Bell inequality.
Closed-form Green functions, surface effects, and the importance of dimensionality in tight-binding metals
Authors: Reuter Matthew G.
Published: July 2010

Closed-form expressions for all elements of a d-dimensional tight-binding metal’s Green function matrix are presented and used to explore edge effects of a surface. We find that, when moving from the surface into the bulk, the number of layers passed before the surfaced substrate behaves like the bulk decreases with dimensionality. In particular, the surface of a one-dimensional substrate becomes indistinguishable from the bulk after O(101–102) layers, a two-dimensional substrate after O(101) layers, and a three-dimensional substrate after O(100) layers. Finally, the effects of substrate dimensionality on molecule-substrate interactions are discussed.
Self-manifestation and universal correction of image distortion in scanning tunneling microscopy with spiral scan
Authors: Wang Junting , Wang Jihui , Hou Yubin , Lu Qingyou
Published: July 2010

We demonstrate that severe distortions may occur but hard to identify in a standard line-by-line scanned scanning tunneling microscope image, deforming the atomic lattice into a completely different structure type and leading to a wrong interpretation of the data. We also show that a spiral scan image can reveal the details of the drifting by causing the atomic rows to bend with the curvatures being closely related to the extent and direction of the drifting. By straightening the curved atomic rows, the true atomic arrangement can thus be precisely recovered.
Heterostructure growth of a single-crystal hexagonal AlN (0001) layer on cubic diamond (111) surface
Authors: Hirama Kazuyuki , Taniyasu Yoshitaka , Kasu Makoto
Published: July 2010

We demonstrate heterostructure growth of a hexagonal AlN (0001) layer on cubic diamond (111) surface and investigate the interface structure in order to achieve AlN/diamond heterojunction devices. From the initial growth, the single-crystal AlN (0001) layer grows on the diamond (111) surface with an in-plane epitaxial relationship [101¯0]AlN//[11¯0]diamond. A high-resolution transmission electron microscope image shows an abrupt interface. Misfit dislocations are distributed periodically at the heterointerface due to the large lattice mismatch between AlN and diamond. Compared with the in-plane epitaxial relationship [112¯0]AlN//[11¯0]diamond, [101¯0]AlN//[11¯0]diamond is energetically preferred because it has a higher bond density and, therefore, lower interfacial energy.
Influence of the anion on the electrical conductivity and glass formation of 1-butyl-3-methylimidazolium ionic liquids
Authors: Leys Jan , Rajesh Ravindran Nair , Menon Preethy Chirukandath , Glorieux Christ , Longuemart Stéphane , Nockemann Peter , Pellens Michael , Binnemans Koen
Published: July 2010

Six ionic liquids based on the 1-butyl-3-methylimidazolium cation have been studied. As anions Cl−, Br−, I−, [NCS]−, [N(CN)2]−, and [BF4]− were selected. The electrical conductivities were determined between 173 and 393 K based on impedance measurements in the frequency range from 0.1 to 107 Hz. The electrical conductivity increases, whereas the glass transition temperature, the fragility, and the low temperature activation energy decrease with increasing anion size. The results can be understood from the changing anion-cation interaction strength with changing anion size and from the energy landscape interpretation of the glass transition dynamics.
Scattering analysis of two-dimensional electrons in AlGaN/GaN with bulk related parameters extracted by simple parallel conduction extraction method
Authors: Lisesivdin S. B. , Yildiz A. , Balkan N. , Kasap M. , Ozcelik S. , Ozbay E.
Published: July 2010

We carried out the temperature (22–350 K) and magnetic field (0.05 and 1.4 T) dependent Hall mobility and carrier density measurements on Al0.22Ga0.78N/GaN heterostructures with AlN interlayer grown by metal-organic chemical-vapor deposition. Hall data is analyzed with a simple parallel conduction extraction method and temperature dependent mobility and carrier densities of the bulk and two-dimensional (2D) electrons are extracted successfully. The results for the bulk carriers are discussed using a theoretical model that includes the most important scattering mechanisms that contribute to the mobility. In order to investigate the mobility of two-dimensional electron gas, we used a theoretical model that takes into account the polar optical phonon scattering, acoustic phonon scattering, background impurity scattering, and interface roughness scattering in 2D. In these calculations, the values are used for the deformation potential and ionized impurity density values were obtained from the bulk scattering analysis. Therefore, the number of fitting parameters was reduced from four to two.
Infinite-dimensional symmetries of two-dimensional generalized Burgers equations
Authors: Güngör F.
Published: July 2010

The conditions for a class of generalized Burgers equations which a priori involve nine arbitrary functions of one or two variables to allow an infinite-dimensional symmetry algebra are determined. Although this algebra can involve up to two arbitrary functions of time, it does not allow a Virasoro subalgebra. This result reconfirms a long-standing fact that variable coefficient generalizations of a nonintegrable equation should be expected to remain as such.
Nanostripe domains in CaCu3Ti4O12: Its origin and influences on high permittivity response
Authors: Sarkar Sudipta , Chaudhuri B. K. , Yang H. D.
Published: July 2010

Internal nanodomains in the form of stripe or nanostripe domains (NSDs) have been found in high permittivity CaCu3Ti4O12 (CCTO) prepared by ceramic route. High resolution transmission electron microscopy study detects plane defects along the domain boundaries. Electron diffraction patterns indicate the existence of probable twinning in CCTO, resulting plane defects. X-ray photoelectron spectroscopy studies also detect Cu1+ and Ti3+ demonstrating the presence of compositional disorder in CCTO which leads to lattice dislocations along the domain boundary regions. Highly disordered plane defects are responsible for creation of NSDs and act as insulating barriers. Thus, high permittivity is achieved through internal barrier layer capacitance within CCTO grains. Present observation of NSDs in CCTO and their origin finally confirm the extrinsic mechanism of the huge dielectric response of CCTO ceramic.
The study of oxygen molecules on Pt (111) surface with high resolution x-ray photoemission spectroscopy
Authors: Kim Yong Su , Bostwick Aaron , Rotenberg Eli , Ross Philip N. , Hong Soon Cheol , Mun Bongjin Simon
Published: July 2010

By using high resolution x-ray photoelectron spectroscopy, we show that inelastic scattering of photoelectron at low temperature (30–50 K) generates two kinds of oxygen species on Pt (111) surface. Intense synchrotron radiation source dissociates oxygen molecules into chemisorbed atomic oxygen and induces the formation of PtO on the surface. Estimated coverage of dissociated atomic oxygen is 0.5 ML, suggesting possible formation of p(2×1) surface structure, while PtO coverage shows saturation coverage of 0.5 ML. Molecular oxygen dosed at 30 K undergoes thermally activated transition from physisorbed to chemisorbed state at around 40 K.
Monte Carlo simulations of single- and multistep enzyme-catalyzed reaction sequences: Effects of diffusion, cell size, enzyme fluctuations, colocalization, and segregation
Authors: Anderson James B. , Anderson Louise E. , Kussmann Jörg
Published: July 2010

Following the discovery of slow fluctuations in the catalytic activity of an enzyme in single-molecule experiments, it has been shown that the classical Michaelis–Menten (MM) equation relating the average enzymatic velocity and the substrate concentration may hold even for slowly fluctuating enzymes. In many cases, the average velocity is that given by the MM equation with time-averaged values of the fluctuating rate constants and the effect of enzyme fluctuations is simply averaged out. The situation is quite different for a sequence of reactions. For colocalization of a pair of enzymes in a sequence to be effective in promoting reaction, the second must be active when the first is active or soon after. If the enzymes are slowly varying and only rarely active, the product of the first reaction may diffuse away before the second enzyme is active, and colocalization may have little value. Even for single-step reactions the interplay of reaction and diffusion with enzyme fluctuations leads to added complexities, but for multistep reactions the interplay of reaction and diffusion, cell size, compartmentalization, enzyme fluctuations, colocalization, and segregation is far more complex than for single-step reactions. In this paper, we report the use of stochastic simulations at the level of whole cells to explore, understand, and predict the behavior of single- and multistep enzyme-catalyzed reaction systems exhibiting some of these complexities. Results for single-step reactions confirm several earlier observations by others. The MM relationship, with altered constants, is found to hold for single-step reactions slowed by diffusion. For single-step reactions, the distribution of enzymes in a regular grid is slightly more effective than a random distribution. Fluctuations of enzyme activity, with average activity fixed, have no observed effects for simple single-step reactions slowed by diffusion. Two-step sequential reactions are seen to be slowed by segregation of the enzymes for each step, and results of the calculations suggest limits for cell size. Colocalization of enzymes for a two-step sequence is seen to promote reaction, and rates fall rapidly with increasing distance between enzymes. Low frequency fluctuations of the activities of colocalized enzymes, with average activities fixed, can greatly reduce reaction rates for sequential reactions.
Enhanced diffusion upon amorphous-to-nanocrystalline phase transition in Mo/B4C/Si layered systems
Authors: de Rooij-Lohmann V. I. T. A. , Yakshin A. E. , van de Kruijs R. W. E. , Zoethout E. , Kleyn A. W. , Keim E. G. , Gorgoi M. , Schäfers F. , Brongersma H. H. , Bijkerk F.
Published: July 2010

The effect of an amorphous-to-nanocrystalline phase transition on the diffusion across an interface layer of subnanometer thickness has been investigated in real-time. The diffusion in the Mo/B4C/Si thin film structure studied was found to instantaneously enhance by an order of magnitude upon the formation of nanocrystals inducing the atomic-scale onset of grain boundary diffusion.
Relaxation approach for the generation of inhomogeneous distributions of uniformly sized particles
Authors: Hunt J. , Kundtz N. , Landy N. , Smith D. R.
Published: July 2010

For many applications in gradient index devices and photonic crystals, it is necessary to be able to design semicrystalline distributions of particles where the lattice constant of the distribution is an arbitrary function of position. We propose a method to generate such distributions which is physically motivated by a system of interacting particles, and apply it to the design and implementation of a microwave gradient index lens. While the demonstration was preformed at microwave wavelengths, this technique would also be particularly useful for designing devices for operation at IR and visible wavelengths where the fabrication of distributions of uniformly sized holes or columns is very easy.
Mapping available Ocean Thermal Energy Conversion resources around the main Hawaiian Islands with state-of-the-art tools
Authors: Nihous Gérard C.
Published: July 2010

This paper aims to demonstrate how the evaluation of Ocean Thermal Energy Conversion (OTEC) resources can benefit from currently available high-resolution ocean models. The case of waters around the main Hawaiian Islands is presented because of its relevance to the future development of OTEC. OTEC resources are defined here by ocean temperature differences between water depths of 20 and 1000 m, with little loss of generality. Using state-of-the-art tools like the HYCOM+NCODA (1/12°) model affords the possibility to track changes on a daily basis over a wide area (e.g., 17 °N to 24 °N and 153 °W to 162 °W). An examination of numerical data over a time period of 2 years reveals interesting geographical patterns. It is found that average OTEC temperature differences are consistently higher (by about 1 °C) west of the islands, whereas the amplitude of the yearly cycle globally decreases from north to south as expected. Better OTEC resources in the lee of the islands are attributed to the narrow eastward-flowing Hawaiian Lee Counter Current. All other things being equal, a change of 1 °C in the resource typically would amount to a 15% variation in net OTEC power output.
Silicon nanowire piezoresistance: Impact of surface crystallographic orientation
Authors: Barwicz Tymon , Klein Levente , Koester Steven J. , Hamann Hendrik
Published: July 2010

We investigate piezoresistance in lithographically defined silicon nanowires of various cross-sectional aspect ratios. Both ⟨110⟩- and ⟨100⟩-oriented nanowires are investigated under ⟨110⟩-oriented strain. The nanowire thickness is varied from 23 to 45 nm and the nanowire width is varied from 5 to 113 nm. Our data shows piezoresistance in silicon nanowires being a surface induced effect with {110} surfaces inducing a much larger piezoresistance than {100} surfaces. This is consistent with a higher density of surface states on {110} surfaces than on {100} surfaces. Our experimental findings support recent computational work pointing toward surface states being the source of giant piezoresistance in silicon nanowires.
Graphene oxide nanosheets based organic field effect transistor for nonvolatile memory applications
Authors: Kim Tae-Wook , Gao Yan , Acton Orb , Yip Hin-Lap , Ma Hong , Chen Hongzheng , Jen Alex K.-Y.
Published: July 2010

Reversible switching characteristics of organic nonvolatile memory transistors (ONVMTs) using chemically synthesized graphene oxide (GO) nanosheets as a charge-trapping layer are reported. The transfer curves of GO based ONVMTs showed large gate bias dependent hysteresis with threshold voltage shifts over 20 V. After writing and erasing, stored data were well maintained showing more than two orders of ON/OFF ratio (ION/IOFF=∼102) for 104 s. These results suggest that GO nanosheets are one potential candidate as the charge-trapping layer in ONVMTs.
Atomic scale characterization of titanium Ohmic contacts to SiC using three dimensional atom probe tomography and high resolution transmission electron microscopy
Authors: Maneshian M. H. , Mahdak K. C. , Kuo F. L. , Hwang J. Y. , Banerjee R. , Shepherd N. D.
Published: July 2010

Three dimensional atom probe tomography coupled with high resolution transmission electron microscopy were used to analyze the structural and compositional transitions across interfaces of Ti Ohmic contacts on SiC. The results conclusively show that during the interfacial reaction carbon diffuses into the Ti layer, with the reaction zone extending beyond the immediate interface. The resultant TiC/TiCx interfacial layer provides a graded work function profile between the Ti and SiC, and facilitates low contact resistance which was measured by the transmission line, current-voltage method.
High quality relaxed GaAs quantum dots in GaP matrix
Authors: Shamirzaev Timur S. , Abramkin Demid S. , Gutakovskii Anton K. , Putyato Mikhail A.
Published: July 2010

A system of GaAs self-assembled quantum dots (QDs) embedded in GaP matrix was studied by means of transmission electron microscopy, steady-state, and transient photoluminescence. Unusually, the QDs are fully unstrained but they have no nonradiative centers introduced by dislocations at GaAs/GaP heterostructure. The band alignment in the QDs is shown to be of type I.
Time-varying ionic properties of a liquid-crystal cell
Authors: Liu Hsuan-Hung , Lee Wei
Published: July 2010

This work investigates time-evolved ionic characteristics of a homogeneously aligned cell composed of a low-resistivity nematic liquid crystal. The influence of montmorillonite as a nanoadditive is studied on the dielectric spectrum of the cell. The incorporation of the inorganic nanoplatelets into the nematic leads to decrease in conductivity in the frequency range from 10 Hz to at least 10 kHz. The dielectric spectroscopic results show that the conductivity, ionic concentration, and diffusion constant of both undoped and doped cells are strongly time-dependent after the cell fabrication.