bluuebunny/crossref_metadata_2025 huggingface dataset:
Gadolinium‐induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons
Authors: Xia Qing , Feng Xudong , Huang Haifeng , Du Lingyan , Yang Xiaoda , Wang Kui
Published: December 2010

J. Neurochem. (2011) 117, 38–47.

Introduction of Gadolinium (Gd) to the nervous system is linked to the development of neurotoxicity involving both oxidative and endoplasmic reticulum (ER) stress. Gd levels (0.2–20 μm) in the form of gadolinium trichloride (GdCl3) cause neurotoxicity in vitro. We investigated the signaling pathways in primary cultured rat cortical neurons and tested whether GdCl3 induced oxidative and ER stress. Results showed that Gd‐induced neural cell death followed a rapid accumulation of intracellular reactive oxygen species. In addition, Gd exposure resulted in spliced X‐box binding protein 1 mRNA and increased expression of binding immunoglobulin protein, thus activating transcription factor 4 (ATF4), ATF6, and C/EBP homologous protein mRNA. Up‐regulated expression of binding immunoglobulin protein is a hallmark of ER stress and C/EBP homologous protein is an ER stress‐related pro‐apoptotic transcription factor. Activation of ER stress downstream substrates, inositol‐requiring kinase 1 and ATF6, was also observed in Gd‐treated cells. The neurotoxic effects of Gd were blocked by the antioxidant N‐acetylcysteine. Results demonstrated that Gd‐induced cytotoxicity in neurons occurs via oxidative injury and ER stress‐related signal transduction, thus offering new insight into the neurotoxicology of gadolinium.
p38 Mitogen‐activated protein kinase and PI3‐kinase are involved in up‐regulation of mu opioid receptor transcription induced by cycloheximide
Authors: Kim Do Kyung , Hwang Cheol Kyu , Wagley Yadav , Law Ping‐Yee , Wei Li‐Na , Loh Horace H.
Published: December 2010

J. Neurochem. (2011)116, 1077–1087.

Despite several decades of efforts to develop safer, efficacious, and non‐addictive opioids for pain treatment, morphine remains the most valuable painkiller in contemporary medicine. Morphine and endogenous mu opioid peptides exert their pharmacological actions mainly through the mu opioid receptor (MOR). Analgesic effects of opioids in animals are dependent on the MOR expression levels, as demonstrated by studies of MOR‐knockout mice (homo/heterozygotes) and MOR‐less expressing mice. Surprisingly, in the course of our investigation to understand the mechanisms involved in the regulation of MOR gene expression, cycloheximide (CHX), a known protein synthesis inhibitor, markedly induced accumulation of MOR mRNAs in both MOR‐negative and ‐positive cells. This induction was blocked by inhibitors of phosphoinositide 3‐kinase (PI3‐K) and p38 MAPK, but not by a p42/44 MAPK inhibitor.In vitro, CHX was found to activate the MOR promoter and this activation was suppressed by inhibition of PI3‐K. The transcriptional activator Sox18 was recruited to the MOR promoter in CHX‐treated cells and this recruitment was also inhibited by the PI3‐K and p38 MAPK inhibitors, Ly294002 and SB203580, respectively. Consistently, acetylation of histone H3 and induction of H3‐K4 methylation were detected while reductions of histone deacetylase 2 binding and H3‐K9 methylation were observed on the promoter. Furthermore, the MOR mRNA accumulation was almost completely inhibited in the presence of actinomycin‐D, indicating that this effect occurs mainly through activation of the transcriptional machinery. These observations suggest that CHX directly induces MOR gene transcription by recruiting the active transcription factor Sox18 to the MOR promoter through PI3‐ and/or p38 MAPK pathways.
Dramatic increase in readthrough acetylcholinesterase in a cellular model of oxidative stress
Authors: Härtl Ricarda , Gleinich Anne , Zimmermann Martina
Published: December 2010

J. Neurochem.(2011)116, 1088–1096.

Moderate, transient oxidative stress is achieved in SH‐SY5Y cells using tertiary butylhydroperoxide as oxidant. Over a recovery period of 24 h, the enzymatic activity and protein levels of the acetylcholinesterase (AChE) splice variants tailed AChE (AChE‐T) and readthrough AChE (AChE‐R) are monitored. Their time‐dependent correlation to pro‐ and anti‐apoptotic factors, namely caspase 3 and Bcl‐2, respectively, as well as lactate dehydrogenase release as a measure of cell viability is assessed. A distinctly different expression pattern of AChE‐T as compared with AChE‐R is recorded, in that AChE‐T shows only a very slight increase over a 6 h time period. In contrast, AChE‐R rises continuously during the recovery period, reaching peak intracellular levels that are up to six times higher than control levels 3–4 h post‐stress, and is released from cells in substantial amounts. Moreover, anti‐apoptotic Bcl‐2 increases significantly, peaking 2–3 h after this AChE‐R peak has occurred. We believe this study presents the first work that demonstrates – without relying on techniques of over‐expression – the time‐dependent correlation between apoptotic processes and related rescue mechanisms involving AChE isoforms in a neuronal cell line.
Oxidative stress‐induced oligomerization inhibits the activity of the non‐receptor tyrosine phosphatase STEP61
Authors: Deb Ishani , Poddar Ranjana , Paul Surojit
Published: December 2010

J. Neurochem.(2011)116, 1097–1111.

The neuron‐specific tyrosine phosphatase STriatal Enriched Phosphatase (STEP) is emerging as an important mediator of glutamatergic transmission in the brain. STEP is also thought to be involved in the etiology of neurodegenerative disorders that are linked to oxidative stress such as Alzheimer’s disease and cerebral ischemia. However, the mechanism by which oxidative stress can modulate STEP activity is still unclear. In this study, we have investigated whether dimerization may play a role in regulating the activity of STEP. Our findings show that STEP61, the membrane associated isoform, can undergo homodimerization under basal conditions in neurons. Dimerization of STEP61involves intermolecular disulfide bond formation between two cysteine residues (Cys 65 and Cys 76 respectively) present in the hydrophobic region at the N‐terminus specific to STEP61. Oxidative stress induced by hydrogen peroxide leads to a significant increase in the formation of dimers and higher‐order oligomers of STEP61. Using two substrates,para‐nitrophenylphosphate and extracellular‐regulated kinase MAPK we further demonstrate that oligomerization leads to a significant reduction in its enzymatic activity.
Dendritic trafficking of brain‐derived neurotrophic factor mRNA: regulation by translin‐dependent and ‐independent mechanisms
Authors: Wu Yen‐Ching , Williamson Rebecca , Li Zhi , Vicario Annalisa , Xu Jerry , Kasai Masataka , Chern Yijuang , Tongiorgi Enrico , Baraban Jay M.
Published: December 2010

J. Neurochem. (2011) 116, 1112–1121.

Dendritic trafficking and translation of brain‐derived neurotrophic factor (BDNF) transcripts play a key role in mediating synaptic plasticity. Recently, we demonstrated that siRNA‐mediated knockdown of translin, an RNA‐binding protein, impairs KCl‐induced dendritic trafficking of BDNF mRNA in cultured hippocampal neurons. We have now assessed whether translin deletion impairs dendritic trafficking of BDNF mRNA in hippocampal neurons in vivo. We have found that translin and its partner protein, trax, undergo dendritic translocation in response to treatment with pilocarpine, a pro‐convulsant muscarinic agonist that increases dendritic trafficking of BDNF mRNA in hippocampal neurons. In translin knockout mice, the basal level of dendritic BDNF mRNA is decreased in CA1 pyramidal neurons. However, translin deletion does not block pilocarpine’s ability to increase dendritic trafficking of BDNF mRNA indicating that the requirement for translin in this process varies with the stimulus employed to drive it. Consistent with this inference, we found that dendritic trafficking of BDNF mRNA induced by bath application of recombinant BDNF in cultured hippocampal neurons, is not blocked by siRNA‐mediated knockdown of translin. Taken together, these in vivo and in vitro findings indicate that dendritic trafficking of BDNF mRNA can be mediated by both translin‐dependent and ‐independent mechanisms.
SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post‐synaptic specializations of inhibitory synapses
Authors: Fukaya Masahiro , Kamata Akifumi , Hara Yoshinobu , Tamaki Hideaki , Katsumata Osamu , Ito Naoki , Takeda Shin’ichi , Hata Yutaka , Suzuki Tatsuo , Watanabe Masahiko , Harvey Robert J. , Sakagami Hiroyuki
Published: December 2010

J. Neurochem. (2011) 116, 1122–1137.

SynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A‐resistant Arf‐GEF/IQSEC family and was originally identified by screening for mRNA species associated with the post‐synaptic density fraction. In this study, we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin incorporation assays. Immunohistochemical analysis reveals that synArfGEF is present in somata and dendrites as puncta in close association with inhibitory synapses, whereas immunoelectron microscopic analysis reveals that synArfGEF localizes preferentially at post‐synaptic specializations of symmetric synapses. Using yeast two‐hybrid and pull down assays, we show that synArfGEF is able to bind utrophin/dystrophin and S‐SCAM/MAGI‐2 scaffolding proteins that localize at inhibitory synapses. Double immunostaining reveals that synArfGEF co‐localizes with dystrophin and S‐SCAM in cultured hippocampal neurons and cerebellar cortex, respectively. Both β‐dystroglycan and S‐SCAM were immunoprecipitated from brain lysates using anti‐synArfGEF IgG. Taken together, these findings suggest that synArfGEF functions as a novel regulator of Arf6 at inhibitory synapses and associates with the dystrophin‐associated glycoprotein complex and S‐SCAM.
Individualistic species limitations of climate‐induced range expansions generated by meso‐scale dispersal barriers
Authors: Keith Sally A. , Herbert Roger J.H. , Norton Paul A. , Hawkins Stephen J. , Newton Adrian C.
Published: December 2010

Aim  Evidence indicates that species are responding to climate change through distributional range shifts that track suitable climatic conditions. We aim to elucidate the role of meso‐scale dispersal barriers in climate‐tracking responses.

Location  South coast of England (the English Channel).

Methods  Historical distributional data of four intertidal invertebrate species were logistically regressed against sea surface temperature (SST) to determine a climate envelope. This envelope was used to estimate the expected climate‐tracking response since 1990 along the coast, which was compared with observed range expansions. A hydrodynamic modelling approach was used to identify dispersal barriers and explore disparities between expected and observed climate tracking.

Results  Range shifts detected by field survey over the past 20 years were less than those predicted by the changes that have occurred in SST. Hydrodynamic model simulations indicated that physical barriers produced by complex tidal currents have variably restricted dispersal of pelagic larvae amongst the four species.

Main conclusions  We provide the first evidence that meso‐scale hydrodynamic barriers have limited climate‐induced range shifts and demonstrate that life history traits affect the ability of species to overcome such barriers. This suggests that current forecasts may be flawed, both by overestimating range shifts and by underestimating climatic tolerances of species. This has implications for our understanding of climate change impacts on global biodiversity.
THE DAYLIGHT SAVING TIME ANOMALY IN STOCK RETURNS: FACT OR FICTION?
Authors: Gregory‐Allen Russell , Jacobsen Ben , Marquering Wessel
Published: December 2010

Stock market returns in 22 markets around the world show no evidence of a daylight saving time effect. Returns on the days following a switch from or to daylight saving time do not behave any differently from stock market returns on any other day of the week or month. These results reject earlier conclusions in the literature—based on less data—that investors’ mood changes induced by changes in sleep patterns significantly affect stock returns.
CORPORATE HEDGING AND SHAREHOLDER VALUE
Authors: Aretz Kevin , Bartram Söhnke M.
Published: December 2010

Although theory suggests that corporate hedging can increase shareholder value in the presence of capital market imperfections, empirical studies show overall mixed support for rationales of hedging with derivatives. Although various empirical challenges and limitations advise some caution with regard to the interpretation of the existing evidence, the results are consistent with derivatives use being just one part of a broader financial strategy that considers the type and level of financial risks, the availability of risk management tools, and the operating environment of the firm. Moreover, corporations rely heavily on pass‐through, operational hedging, and foreign currency debt to manage financial risk.
DETERMINANTS OF CAPITAL STRUCTURE IN BUSINESS START‐UPS: THE ROLE OF NONFINANCIAL STAKEHOLDER RELATIONSHIP COSTS
Authors: Franck Tom , Huyghebaert Nancy
Published: December 2010

According to the finance literature, nonfinancial stakeholders (NFS), such as customers, suppliers, and employees, take into account their expected liquidation costs when dealing with a firm. In this framework, firms can influence their probability of liquidation by choosing an appropriate capital structure. Also, the literature suggests NFS bargaining power may affect firm financing decisions. In the current article we investigate these ideas for initial financing decisions by business start‐ups, where ex ante failure risk is high and NFS must decide whether to make relationship‐specific investments. We find that start‐ups imposing larger costs on their NFS following liquidation significantly reduce leverage. This effect is strengthened when suppliers have greater bargaining power. We also document a marginally negative effect of NFS liquidation costs on the proportion of bank loans. Finally, business start‐ups rely less on bank loans when customers and suppliers are in a powerful bargaining position.
Comparing Partial and Total Tibial‐Nerve Axotomy: Long‐Term Effects on Prevalence and Location of Evoked Pain Behaviors
Authors: Unal‐Cevik Isin , Oaklander Anne Louise
Published: December 2010

Monophasic (one‐time) nerve injuries heal without clinically significant residua in most cases, but rare individuals are left with neuropathic pain, even after seemingly minor lesions. The effects of lesion size on risk for chronic pain persistence are not well understood, particularly as concerns the complex regional pain syndrome, which is defined in part by pain “disproportionate” to the severity of the causative lesion, and extending outside the autonomous territory of a single nerve. To better clarify the expected prevalence of pain behaviors after nerve injury, we compared the effects in rats of different‐sized axotomies on the prevalence and location of evoked pain behaviors. To highlight clinical relevance, we also describe a patient with iatrogenic tibial‐nerve injury causing similar chronic neuralgia. Adult male Sprague‐Dawley rats were anesthetized and had either 1/3, 2/3 or their entire left tibial nerves tightly ligated at two sites just below the sciatic trifurcation and the interposed nerve was cut. Unoperated rats provided controls. Sensory function in the tibial and sural‐innervated territories of both plantar hindpaws was assessed for as long as 6 months postoperatively. Soon after surgery, evoked pain behavior developed in the ipsilesional sural‐innervated site in a subset of axotomized rats and recovery was variable. The relationship between lesion size and prevalence and severity of hyperalgesia varied for different pain behaviors, with pinprick hyperalgesia clearly more likely after larger axotomies. In summary, partial tibial‐nerve injury in rats models human disease and suggests that expectations of proportionality between lesion size and development of neuropathic pain may need revision.
Percutaneous Atrial Shunt Closure Using the Novel Occlutech Figulla Device: 6‐Month Efficacy and Safety
Authors: VAN DEN BRANDEN BEN J. L. , POST MARTIJN C. , PLOKKER HERBERT W. M. , TEN BERG JURRIËN M. , SUTTORP MAARTEN J.
Published: December 2010

Background:
 The Occlutech Figulla Occluder is a new innovative device for percutaneous closure of a patent foramen ovale (PFO) and an atrial septum defect (ASD). We describe the safety and efficacy of this new device at 6‐month follow‐up.

Methods:
 All 82 consecutive patients (51% female, mean age 49.0 ± 13.6 years) who underwent percutaneous PFO (n = 48) or ASD (n = 34) closure between October 2008 and October 2009 were included.

Results:
 Implantation success was 100%. The in‐hospital complications were two new onset supraventricular tachycardia (SVT) (2.4%, both ASD patients), nine minimal groin hematoma's (11.0%, 4 PFO and 5 ASD patients), and one transient ST elevation during the procedure (1.2%, ASD patient). During 6 months follow‐up (n = 79), no major complications or reoccurrences of cerebral thrombo‐embolic events did occur. Seven patients (8.9%, 6 PFO and 1 ASD patient) experienced a new SVT. One patient developed a recurrent cerebral hemorrhage 5 months after ASD closure, which appeared not to be related to the procedure. Using contrast transthoracic echocardiography 6 months after PFO closure (n = 45), a residual shunt was present in 30.2% of the patients (small 25.6%, moderate 4.6%, severe 0%). In the ASD group (n = 34), a residual shunt was observed in 32.5% (small 17.7%, moderate 14.7%, severe 2.9%).

Conclusion:
 The Occlutech Figulla Occluder appears to be easy to use, effective, and safe for percutaneous closure of PFO and ASD. We report a low complication rate but a relative high percentage of small residual shunts 6 months after closure. (J Interven Cardiol 2011;24:264–270)
Creating effective and engaging information literacy programmes for the dental curriculum
Authors: Ford P. J. , Hibberd K.
Published: December 2010

In this time of rapid expansion of the scientific knowledge base, subject matter runs the risk of becoming outdated within a relatively short time. Instead of adding more content to already crowded curricula, the focus should be on equipping students to adapt to their changing world. The ability to access, evaluate and apply new knowledge for the benefit of patients has been acknowledged as an important goal for dental education. Information literacy is key to achieving this. A template for an Information Literacy programme for undergraduate students is described. This was embedded within a compulsory course for each of the first and second years of the Bachelor of Oral Health programme and consisted of a hands‐on workshop (attendance voluntary), information literacy quiz, self‐evaluation and a summative assessment task, with the second year of the programme building upon the learning of the previous year. Effectiveness was measured in terms of demonstration of information literacy skills and confidence in using these skills. Integration of this programme within the learning activities and assessment of first‐ and second‐year courses resulted in enhanced information literacy skills and confidence. Self‐perceived high skill levels may be a potential barrier to student engagement with information literacy programmes.
Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's disease*†
Authors: Matheson Sally F , Byrne Gerard J , Dissanayaka Nadeeka NW , Pachana Nancy A , Mellick George D , O'Sullivan John D , Silburn Peter A , Sellbach Anna , Marsh Rodney
Published: December 2010

Aim:  To examine the psychometric properties of a novel anxiety rating scale, the Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD).

Method:  The predictive validity of the GAI was tested against the presence of any DSM‐IV anxiety disorders in 58 PD patients using receiver operating curve analysis. The concurrent validity of this scale was also studied against the state half of the Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and test–retest reliability of the GAI were also examined.

Results:  The GAI displayed good concurrent validity against the STAI and the DSM‐IV. It also showed good internal consistency and test–retest reliability.

Conclusions:  This study suggested that the GAI is an appropriate scale to use in non‐demented PD patients.
Effectiveness of an educational self‐management program for outpatients with chronic heart failure
Authors: OTSU Haruka , MORIYAMA Michiko
Published: December 2010

Aim:  The occurrence rate of chronic heart failure (CHF) in Japan is estimated to be 50 000 per one million persons. It is important for the Japanese medical financial system to institute a program of disease management in order to prevent the deterioration of persons with CHF. However, there are still few studies on the disease management of CHF in Japan. Therefore, the purpose of this study was to provide an educational self‐management program to Japanese outpatients with CHF in order to improve their clinical outcomes.

Methods:  A randomized, controlled trial with 102 outpatients with CHF was conducted. There were 50 participants in the intervention group and 52 participants in the control group. The control group received medical treatment and standard care. In addition to this, the intervention group also received an educational program for 6 months. The program consisted of six nurse‐directed sessions that were provided to each outpatient once per month in a clinical setting for a total of 6 months. A follow‐up session was conducted each month for 6 months. The data collection was carried out at the start of the program and at 3, 6, 9, and 12 months.

Results:  Significant differences could be observed in the primary and secondary outcomes and in the process indicators between the two groups after the program began. In other words, all the indicators improved for the intervention group, compared to the control group. Therefore, this program was considered to be effective.

Conclusion:  Further long‐term care is necessary for outpatients with CHF in order to prevent their deterioration and to maintain their health status, even though this 6 month program did provide them with proper knowledge regarding self‐care for CHF and affected their therapy results.
Identification of forensically important blow fly species (Diptera: Calliphoridae) in China by mitochondrial cytochrome oxidase I gene differentiation
Authors: Liu Qin‐Lai , Cai Ji‐Feng , Chang Yun‐Feng , Gu Yan , Guo Ya‐Dong , Wang Xing‐Hua , Weng Ji‐Fang , Zhong Ming , Wang Xiang , Yang Li , Wu Kun‐Lu , Lan Ling‐Mei , Wang Jiang‐Feng , Chen Yao‐Qing
Published: December 2010

Abstract  Unambiguous and rapid sarcosaphagous insect species identification is an essential requirement for forensic investigations. Although some insect species are difficult to classify morphologically, they can be effectively identified using molecular methods based on similarity with abundant authenticated reference DNA sequences in local databases. However, local databases are still relatively incomplete in China because of the large land area with distinct regional conditions. In this study, 75 forensically important blow flies were collected from 23 locations in 16 Chinese provinces, and a 278‐bp segment of the cytochrome oxidase subunit I gene of all specimens was successfully sequenced. Phylogenetic analysis of the sequenced segments showed that all Calliphorid specimens were properly assigned into nine species with relatively strong supporting values, thus indicating that the 278‐bp cytochrome oxidase subunit one region is suitable for identification of Calliphorid species. The clear difference between intraspecific threshold and interspecific divergence confirmed the potential of this region for Calliphorid species identification, especially for distinguishing between morphologically similar species. Intraspecific geographic variations were observed in Lucilia sericata (Meigen, 1826) and Lucilia caesar (Linnaeus, 1758).
Photoperiod Regulates Lung‐associated Immunological Parameters and Melatonin Receptor (Mel1aand Mel1b) in Lungs of a Tropical Bird,Perdicula asiatica
Authors: Kharwar Rajesh Kumar , Haldar Chandana
Published: December 2010

We accessed the effects of different photoperiodic regimes,i.e.long (LP; 20L:4D), short (SP; 4L:20D) and natural day photoperiod during reproductively inactive and reproductively active phase on immune parameters of lungs and general immunity ofPerdicula asiatica. SP increased bronchus‐associated lymphoid tissue (BALT) and non‐BALT nodule size, total leukocyte count, lymphocyte count, plasma melatonin level, percent stimulation ratio of lymphocytes and decreased testicular activity (weight and testosterone level). LP during both the reproductive phases decreased the above‐mentioned immune parameters suggesting that photoperiod might be regulating lung‐associated immune system (LAIS)viamelatonin. We also extended our study to note the expression of melatonin receptor types Mel1aand Mel1bin lung tissue to support our above statement. Western blot analysis showed significant increase in expression of Mel1aand Mel1breceptor types under SP conditions and decreased expression under LP condition when compared with control group of both reproductive phases. This suggests the probable involvement of Mel1aand Mel1breceptors in mediation of photoperiodic signals to LAIS.P. asiaticais a photoperiodic bird hence photoperiodically regulated melatonin hormone and its receptors in the lung might be responsible for modulation of lung‐associated immunity.
Photoreaction in BLUF Receptors: Proton‐coupled Electron Transfer in the Flavin‐Gln‐Tyr System†
Authors: Udvarhelyi Anikó , Domratcheva Tatiana
Published: December 2010

Photoinduced electron transfer from tyrosine to the flavin chromophore is involved in activation of BLUF (sensor of blue light using FAD) photoreceptors. We studied the electron transfer (ET) coupled with proton‐transfer (PT) reactions, by means of XMCQDPT2//CASSCF calculations on a molecular cluster model. By defining a minimum active space in the CASSCF calculations, we could compute the entire photoreaction pathway. We find that the crossing of the locally excited and ET states is located along the flavin bond‐stretching coordinate. The ET state is stabilized by a proton transfer from the electron donor to the electron acceptor. We mapped two different PT pathways from tyrosine to flavin via the conserved glutamine. These reactions generate a tautomeric form of glutamine. Along the PT coordinates, we find geometries where the ET and the electronic ground states degenerate. At the state crossing structures, either formation of the ground state biradical intermediate or a relaxation back to the Franck–Condon minimum takes places. The computed relaxation pathways reveal that the hydrogen bonds involving glutamine in the chromophore‐binding pocket control BLUF photoefficiency.
Light‐generated Paramagnetic Intermediates in BLUF Domains†
Authors: Weber Stefan , Schroeder Claudia , Kacprzak Sylwia , Mathes Tilo , Kowalczyk Radoslaw M. , Essen Lars‐Oliver , Hegemann Peter , Schleicher Erik , Bittl Robert
Published: December 2010

Blue‐light sensitive photoreceptory BLUF domains are flavoproteins, which regulate various, mostly stress‐related processes in bacteria and eukaryotes. The photoreactivity of the flavin adenine dinucleotide (FAD) cofactor in three BLUF domains from Rhodobacter sphaeroides, Synechocystis sp. PCC 6803 and Escherichia coli have been studied at low temperature using time‐resolved electron paramagnetic resonance. Photoinduced flavin triplet states and radical‐pair species have been detected on a microsecond time scale. Differences in the electronic structures of the FAD cofactors as reflected by altered zero‐field splitting parameters of the triplet states could be correlated with changes in the amino‐acid composition of the various BLUF domains’ cofactor binding pockets. For the generation of the light‐induced, spin‐correlated radical‐pair species in the BLUF domain from Synechocystis sp. PCC 6803, a tyrosine residue near the flavin’s isoalloxazine moiety plays a critical role.
A Conversation with Jef Teugels
Authors: Fisher Nicholas I.
Published: December 2010

Jozef Lodewijk Maria Teugels was born in Londerzeel, Belgium, on February 20, 1939. He received his high school education at Sint‐Lievenscollege in Antwerp. He obtained a Candidate diploma in Physics in 1961 and a License degree in Mathematics in 1963 at the Catholic University of Louvain. After serving one year in the army, he obtained his MSc in 1966 and his PhD in 1967 at Purdue University, with Marcel F. Neuts as advisor. In 1967 he was appointed at the Catholic University of Louvain and promoted to Full Professor in 1973. He remained in Leuven until his retirement in 2004. He chaired the Department of Mathematics over the periods 1970–77 and 1982–89. He has held visiting positions at numerous universities in the United Kingdom, Portugal, the United States of America, South Africa, Japan, Indonesia and Australia.
Estimation of Asymmetric Stochastic Volatility Models: Application to Daily Average Prices of Energy Products
Authors: Montero José‐María , Fernández‐Avilés Gema , García María‐Carmen
Published: December 2010

Energy supply and demand, and as a consequence energy prices, are likely to represent one of the biggest challenges of the 21st century. Commodity markets exhibit increased volatility when there is little or no underutilized supply capability to meet natural fluctuations in demand. In the case of energy markets, the large capital requirements and significant lead times associated with energy production and delivery make them more susceptible to the imbalances in supply capability and demand. Energy price volatility has destructive impact on market agents, and this impact is intensified when the prices exhibit asymmetric volatility. This article pursues two aspects of the issue. First we consider general aspects, especially the asymmetric pattern of volatility of daily returns of different types of energy products. Then, we analyze the behaviour of daily returns by using traditional models of volatility that include AGARCH, TGARCH, EGARCH, and ARSV strategies, as well as a threshold asymmetric autoregressive stochastic volatility (TA‐ARSV) model that we propose. The energy products considered in this analysis are probably the most relevant energy products for the economic activity of the nations and the economic relations between countries: Crude Oil (OPEC reference basket and London Brent index), Gasoline, Natural Gas, Butane, and Propane. We use spot prices and the time reference ranges from 1986–1993 to 2009 depending on the product.
Development of a predicted physical map of microsatellite locus positions for pinnipeds, with wider applicability to the Carnivora
Authors: OSBORNE AMY J. , BRAUNING RUDIGER , SCHULTZ JENNIFER K. , KENNEDY MARTIN A. , SLATE JON , GEMMELL NEIL J.
Published: December 2010

Understanding genetic variation responsible for phenotypic differences in natural populations is significantly hampered by a lack of genomic data for many species. Levels of variation can, however, be estimated using microsatellite markers, which may be useful for relating individual fitness to genetic diversity. Prior studies have demonstrated correlations between heterozygosity and individual fitness in some species. These correlations are sometimes driven by a subset of markers, and it is unclear whether this is because those markers best reflect genome‐wide heterozygosity, or whether they are linked to fitness‐related genes. Differentiating between these scenarios is hindered when the genomic location of markers is unknown. Here, we develop a predicted genomic map of pinniped microsatellite loci based on conservation of primary sequence and genomic location between dog, cat and giant panda. We mapped 210 of 260 (81%) microsatellites from pinnipeds to locations in dog, cat and giant panda genomes. Based on the demonstrable synteny between the genomes of closely related taxa within the Carnivora, we use these data to identify those microsatellites with the greatest chance of cross‐species amplification success and demonstrate successful amplification of 21 of 26 loci for cat, dog and two seal species. We also demonstrate the potential to identify candidate genes that may underpin the functional relationship with individual fitness. Overall, we show that this approach provides a rapid and robust method to elucidate genome organisation for nonmodel organisms and have established a resource that facilitates further genetic research on pinnipeds that also has wider applicability to other carnivores.
Influence of Planet Pin Stiffness on Load Sharing in Planetary Gear Drives
Authors: Montestruc Alfred N.
Published: December 2010

Others have done significant work on the subject of load sharing among the planets of planetary gear drives; a brief review of that work is presented. Little work has been done, however, to evaluate the utility of the Hicks type flexible planet pins in improvement of load sharing in a planetary gear stage. This work shows the potential value of the three variations of the Hicks type flexible planet pin used on cantilever carriers, and a new design of a low spring constant planet pin that can be used on straddle type carriers. This is done by the calculation of the spring constants of gear meshes, bearings, and various designs of planet pins using the finite element method for a specific design of a planetary gear stage with spur gears and eight planets. The result showed significant differences. Low spring constant flexible pins are shown to have significantly superior load sharing characteristics.
Modified Reduced Gradient With Realization Sorting for Hard Equality Constraints in Reliability-Based Design Optimization
Authors: Ho Chun-Min , Chan Kuei-Yuan
Published: December 2010

In this work, the presence of equality constraints in reliability-based design optimization (RBDO) problems is studied. Relaxation of soft equality constraints in RBDO and its challenges are briefly discussed, while the main focus is on hard equalities that cannot be violated even under uncertainty. Direct elimination of hard equalities to reduce problem dimensions is usually suggested; however, for nonlinear or black-box functions, variable elimination requires expensive root- finding processes or inverse functions that are generally unavailable. We extend the reduced gradient methods in deterministic optimization to handle hard equalities in RBDO. The efficiency and accuracy of the first- and second-order predictions in reduced gradient methods are compared. Results show that the first-order prediction is more efficient when realizations of random variables are available. Gradient-weighted sorting with these random samples is proposed to further improve the solution efficiency of the reduced gradient method. Feasible design realizations subject to hard equality constraints are then available to be implemented with state-of-the-art sampling techniques for RBDO problems. Numerical and engineering examples show the strength and simplicity of the proposed method.
Hot Spots of Integrase Genotypic Changes Leading to HIV-2 Resistance to Raltegravir
Authors: Charpentier Charlotte , Roquebert Bénédicte , Delelis Olivier , Larrouy Lucile , Matheron Sophie , Tubiana Roland , Karmochkine Marina , Duval Xavier , Chêne Geneviève , Storto Alexandre , Collin Gilles , Bénard Antoine , Damond Florence , Mouscadet Jean-François , Brun-Vézinet Françoise , Descamps Diane
Published: December 2010

We studied seven heavily pretreated HIV-2-infected patients exhibiting a virological failure while receiving a salvage raltegravir-containing regimen. At the time of virological failure, different resistance genetic pathways were observed: T97A-Y143C, Q148K, Q148R, G140S-Q148R, E92Q-Y143R-N155H, and T97A-N155H. Thus, despite a 40% difference in integrase genes between HIV-1 and HIV-2, the genetic pathways leading to raltegravir resistance are similar.
Mechanism of Bactericidal Activity of Microcin L inEscherichia coliandSalmonella enterica
Authors: Morin Natacha , Lanneluc Isabelle , Connil Nathalie , Cottenceau Marie , Pons Anne Marie , Sablé Sophie
Published: December 2010

For the first time, the mechanism of action of microcin L (MccL) was investigated in live bacteria. MccL is a gene-encoded peptide produced byEscherichia coliLR05 that exhibits a strong antibacterial activity against relatedEnterobacteriaceae, includingSalmonella entericaserovars Typhimurium and Enteritidis. We first subcloned the MccL genetic system to remove the sequences not involved in MccL production. We then optimized the MccL purification procedure to obtain large amounts of purified microcin to investigate its antimicrobial and membrane properties. We showed that MccL did not induce outer membrane permeabilization, which indicated that MccL did not use this way to kill the sensitive cell or to enter into it. Using a set ofE. coliandSalmonella entericamutants lacking iron-siderophore receptors, we demonstrated that the MccL uptake required the outer membrane receptor Cir. Moreover, the MccL bactericidal activity was shown to depend on the TonB protein that transduces the proton-motive force of the cytoplasmic membrane to transport iron-siderophore complexes across the outer membrane. Using carbonyl cyanide 3-chlorophenylhydrazone, which is known to fully dissipate the proton-motive force, we proved that the proton-motive force was required for the bactericidal activity of MccL onE. coli. In addition, we showed that a primary target of MccL could be the cytoplasmic membrane: a high level of MccL disrupted the inner membrane potential ofE. colicells. However, no permeabilization of the membrane was detected.
Enteropathogenic and Enterohemorrhagic
Escherichia coli
Type III Secretion Effector EspV Induces Radical Morphological Changes in Eukaryotic Cells
Authors: Arbeloa Ana , Oates Clare V. , Marchès Oliver , Hartland Elizabeth L. , Frankel Gad
Published: December 2010

Enteropathogenic
Escherichia coli
(EPEC) and enterohemorrhagic
Escherichia coli
(EHEC) are important human pathogens that rely on translocation of type III secretion system (T3SS) effectors for subversion of signal transduction pathways and colonization of the mammalian gut mucosa. While a core set of effectors is conserved between EPEC and EHEC strains, a growing number of accessory effectors that were found at various frequencies in clinical and environmental isolates have been recently identified. Recent genome projects identified
espV
as a pseudogene in EHEC but a putative functional gene in EPEC strains E110019 and E22 and the closely related mouse pathogen
Citrobacter rodentium
. The aim of this study was to determine the distribution of
espV
among clinical EPEC and EHEC strains and to investigate its function and role in pathogenesis.
espV
was found in 16% of the tested strains. While deletion of
espV
from
C. rodentium
did not affect colonization dynamics or fitness in mixed infections, expression of EspV in mammalian cells led to drastic morphological alterations, which were characterized by nuclear condensation, cell rounding, and formation of dendrite-like projections. Expression of EspV in yeast resulted in a dramatic increase in cell size and irreversible growth arrest. Although the role of EspV in infection and its target host cell protein(s) require further investigation, the data point to a novel mechanism by which the T3SS subverts cell signaling.
The CoREST/REST Repressor Is both Necessary and Inimical for Expression of Herpes Simplex Virus Genes
Authors: Zhou Guoying , Te Du , Roizman Bernard
Published: December 2010

Herpes simplex virus type 1 encodes three sets of genes, α, β, and γ, whose expression is sequentially ordered in a cascade fashion. The transactivators of α genes comprise virion protein 16 (VP16) and the cellular proteins octamer binding protein 1 (Oct1) and host factor 1 (HCF1). Efficient transition from α to β gene expression requires the α protein ICP0 (infected cell protein 0). Earlier studies have shown that this protein binds to CoREST and displaces HDAC1 from the CoREST/REST/lysine-specific demethylase 1 (LSD1) repressor complex. Ultimately, the components of the repressor complex are translocated at least in part into the cytoplasm. A key event in activation of α genes is the recruitment of LSD1 to demethylate histones bound to the α gene promoters. LSD1 is unstable in the absence of its partner, CoREST, and raises the question of whether both CoREST and REST are involved in the initiation of transcription of the α genes. Here we show that CoREST or REST small interfering RNAs (siRNAs) destabilize CoREST, REST, LSD1, and Sin3A, another component of the repressor complex. In cells transfected with REST or CoREST siRNA, the accumulation of α proteins and mRNAs is delayed in comparison to those of mock-transfected or control siRNA-transfected cells. The LSD1/CoREST/REST compressor complex is thus sequentially necessary and subsequently inimical for viral gene expression.

IMPORTANCE
Herpes simplex virus type 1 (HSV-1) is globally regulated at the following four checkpoints: (i) the activation of α (immediate-early) genes, (ii) the point of transition from α to β and γ gene expression, (iii) the silencing of viral genes for the establishment of the latent state, and (iv) the reactivation of viral genes on termination of latency. Earlier studies showed that the transition from α to β and γ gene expression involves the suppression of the HDAC1/lysine-specific demethylase 1 (LSD1)/CoREST/REST (HLCR) repressor complex. More recently, this laboratory reported evidence suggesting that in sensory neurons, HSV-1 hijacks the HLCR complex to silence itself for the establishment of latency. This report extends the observation that LSD1 is required for expression of the α genes to show that the HLCR complex is involved in this process. Thus, HSV-1 has evolved an intimate relationship with the HCLR complex to regulate its gene expression and, by extension, its fundamental interactions with its human host.
INVESTIGATIVE STUDIES ON WATER CONTAMINATION IN BANGLADESH: PRIMARY TREATMENT OF WATER SAMPLES AT THE SAMPLING SITE
Authors: SERA K. , ISLAM MD. SHAFIQUL , TAKATSUJI T. , NAKAMURA T. , GOTO S. , TAKAHASHI C. , SAITOH Y.
Published: December 2010

Arsenic concentration in 13 well waters, 9 pond waters, 10 agricultural waters and a coconut juice taken in Comilla district, Bangladesh, where the problem of arsenic pollution is the most severe, was investigated. High-level arsenic is detected even in the well water which has been kept drinking by the people. Relatively high arsenic concentration was detected for some pond and farm waters even though the sampling was performed just after the rainy season and the waters were expected to be highly diluted. Clear relationship was observed in elemental compositions between the pond water and the coconut juice collected at the edge of the water. These results are expected to become the basic information for evaluating the risk of individual food such as cultured fishes, shrimps and farm products, and for controlling total intakes of arsenic. In order to solve the problem of transportation of water samples internationally, a simple method of target preparation performed at the sampling cite was established and its validity was confirmed. All targets were prepared at the sampling cites in this study on the basis of this method.
THE FLAVOR-CHANGING BOTTOM AND ANTISTRANGE QUARK PRODUCTION IN THE ONE-GENERATION TECHNICOLOR MODEL AT THE ILC
Authors: JIA YAN , LIAN CHAO , YANG XIAOYU , PAN HAOSHUAI , WANG XUELEI
Published: December 2010

The Technicolor (TC) model is a dynamical theory without fundamental scalars. Due to the pseudo-Goldstone bosons, there exist some new flavor-changing (FC) couplings in the TC model which can contribute to the production rates of some FC processes. In this paper, we study the [Formula: see text] production process in the one-generation technicolor model (OGTM) at the ILC, i.e. [Formula: see text]. We find that the cross section [Formula: see text] with the OGTM's contributions can be largely enhanced and the [Formula: see text] signal should be observable at the ILC. Our predictions can be viewed as valid estimates of other TC models. Therefore, the process [Formula: see text] may provide a unique window for studying the TC theory.
A SOLUTION TO THE STRONG CP PROBLEM TRANSFORMING THE THETA ANGLE TO THE KM CP-VIOLATING PHASE
Authors: BORDES JOSÉ , CHAN HONG-MO , TSOU SHEUNG TSUN
Published: December 2010

It is shown that in the scheme with a rotating fermion mass matrix (i.e. one with a scale-dependent orientation in generation space) suggested earlier for explaining fermion mixing and mass hierarchy, the theta angle term in the QCD action of topological origin can be eliminated by chiral transformations, while giving still nonzero masses to all quarks. Instead, the effects of such transformations get transmitted by the rotation to the CKM matrix as the KM phase giving, for θ of order unity, a Jarlskog invariant typically of order 10-5, as experimentally observed. Strong and weak CP violations appear then as just two facets of the same phenomenon.
NONPERTURBATIVE EFFECTIVE MODEL FOR THE HIGGS SECTOR OF THE STANDARD MODEL
Authors: SIRINGO FABIO , MAROTTA LUCA
Published: December 2010

A nonperturbative effective model is derived for the Higgs sector of the Standard Model which is described by a simple scalar theory. The renormalized couplings are determined by the derivatives of the Gaussian effective potential that are known to be the sum of infinite bubble graphs contributing to the vertex functions. A good agreement has been found with strong coupling lattice simulations when a comparison can be made.
HARMONIC ANALYSIS OF OSCILLATORS THROUGH STANDARD NUMERICAL CONTINUATION TOOLS
Authors: BIZZARRI FEDERICO , LINARO DANIELE , OLDEMAN BART , STORACE MARCO
Published: December 2010

In this paper, we describe a numerical continuation method that enables harmonic analysis of nonlinear periodic oscillators. This method is formulated as a boundary value problem that can be readily implemented by resorting to a standard continuation package — without modification — such as AUTO, which we used. Our technique works for any kind of oscillator, including electronic, mechanical and biochemical systems. We provide two case studies. The first study concerns itself with the autonomous electronic oscillator known as the Colpitts oscillator, and the second one with a nonlinear damped oscillator, a nonautonomous mechanical oscillator. As shown in the case studies, the proposed technique can aid both the analysis and the design of the oscillators, by following curves for which a certain constraint, related to harmonic analysis, is fulfilled.
A LEVEL SET BASED SHAPE OPTIMIZATION METHOD FOR AN ELLIPTIC OBSTACLE PROBLEM
Authors: Burger Martin , Matevosyan Norayr , Wolfram Marie-Therese
Published: December 2010

In this paper, we construct a level set method for an elliptic obstacle problem, which can be reformulated as a shape optimization problem. We provide a detailed shape sensitivity analysis for this reformulation and a stability result for the shape Hessian at the optimal shape.

Using the shape sensitivities, we construct a geometric gradient flow, which can be realized in the context of level set methods. We prove the convergence of the gradient flow to an optimal shape and provide a complete analysis of the level set method in terms of viscosity solutions. To our knowledge this is the first complete analysis of a level set method for a nonlocal shape optimization problem.

Finally, we discuss the implementation of the methods and illustrate its behavior through several computational experiments.