bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation initiation factors and active sites of protein synthesis co-localize at the leading edge of migrating fibroblasts
Authors: Willett Mark , Brocard Michele , Davide Alexandre , Morley Simon J.
Published: July 2011

Cell migration is a highly controlled essential cellular process, often dysregulated in tumour cells, dynamically controlled by the architecture of the cell. Studies involving cellular fractionation and microarray profiling have previously identified functionally distinct mRNA populations specific to cellular organelles and architectural compartments. However, the interaction between the translational machinery itself and cellular structures is relatively unexplored. To help understand the role for the compartmentalization and localized protein synthesis in cell migration, we have used scanning confocal microscopy, immunofluorescence and a novel ribopuromycylation method to visualize translating ribosomes. In the present study we show that eIFs (eukaryotic initiation factors) localize to the leading edge of migrating MRC5 fibroblasts in a process dependent on TGN (trans-Golgi network) to plasma membrane vesicle transport. We show that eIF4E and eIF4GI are associated with the Golgi apparatus and membrane microdomains, and that a proportion of these proteins co-localize to sites of active translation at the leading edge of migrating cells.
Structural analysis of the Sil1–Bip complex reveals the mechanism for Sil1 to function as a nucleotide-exchange factor
Authors: Yan Ming , Li Jingzhi , Sha Bingdong
Published: July 2011

Sil1 functions as a NEF (nucleotide-exchange factor) for the ER (endoplasmic reticulum) Hsp70 (heat-shock protein of 70 kDa) Bip in eukaryotic cells. Sil1 may catalyse the ADP release from Bip by interacting directly with the ATPase domain of Bip. In the present study we show the complex crystal structure of the yeast Bip and the NEF Sil1 at the resolution of 2.3 Å (1 Å=0.1 nm). In the Sil1–Bip complex structure, the Sil1 molecule acts as a ‘clamp’ which binds lobe IIb of the Bip ATPase domain. The binding of Sil1 causes the rotation of lobe IIb ~ 13.5° away from the ADP-binding pocket. The complex formation also induces lobe Ib to swing in the opposite direction by ~ 3.7°. These conformational changes open up the nucleotide-binding pocket in the Bip ATPase domain and disrupt the hydrogen bonds between Bip and bound ADP, which may catalyse ADP release. Mutation of the Sil1 residues involved in binding the Bip ATPase domain compromise the binding affinity of Sil1 to Bip, and these Sil1 mutants also abolish the ability to stimulate the ATPase activity of Bip.
Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment
Authors: Filomeni Giuseppe , Cardaci Simone , Da Costa Ferreira Ana Maria , Rotilio Giuseppe , Ciriolo Maria Rosa
Published: July 2011

We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N′]copper(II), named [Cu(isaepy)2], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38MAPK (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38MAPK and p53. Similarly, reverse genetics of p38MAPK yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38MAPK/p53. Fuel supplies counteracted [Cu(isaepy)2]-induced apoptosis and AMPK/p38MAPK/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)2] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38MAPK/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)2] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)2] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment.
Mass and relative elution time profiling: two-dimensional analysis of sphingolipids in Alzheimer's disease brains
Authors: Hejazi Leila , Wong Jason W.H. , Cheng Danni , Proschogo Nicholas , Ebrahimi Diako , Garner Brett , Don Anthony S.
Published: July 2011

Current lipidomic profiling methods rely mainly on MS to identify unknown lipids within a complex sample. We describe a new approach, involving LC×MS/MS (liquid chromatography×tandem MS) analysis of sphingolipids based on both mass and hydrophobicity, and use this method to characterize the SM (sphingomyelin), ceramide and GalCer (galactosylceramide) content of hippocampus from AD (Alzheimer's disease) and control subjects. Using a mathematical relationship we exclude the influence of sphingolipid mass on retention time, and generate two-dimensional plots that facilitate accurate visualization and characterization of the different ceramide moieties within a given sphingolipid class, because related molecules align horizontally or vertically on the plots. Major brain GalCer species that differ in mass by only 0.04 Da were easily differentiated on the basis of their hydrophobicity. The importance of our method's capacity to define all of the major GalCer species in the brain samples is illustrated by the novel observation that the proportion of GalCer with hydroxylated fatty acids increased approximately 2-fold in the hippocampus of AD patients, compared with age- and gender-matched controls. This suggests activation of fatty acid hydroxylase in AD. Our method greatly improves the clarity of data obtained in a lipid profiling experiment and can be expanded to other lipid classes.
microRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene
Authors: Gillen Austin E. , Gosalia Nehal , Leir Shih-Hsing , Harris Ann
Published: July 2011

The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a complex temporal and spatial pattern of expression that is controlled by multiple cis-acting elements interacting with the basal promoter. Although significant progress has been made towards understanding these genomic elements, there have been no reports of post-transcriptional regulation of CFTR by miRNAs (microRNAs). In the present study, we identify two miRNAs, hsa-miR-145 and hsa-miR-494, which regulate CFTR expression by directly targeting discrete sites in the CFTR 3′ UTR (untranslated region). We show that at least 12 miRNAs are capable of repressing endogenous CFTR mRNA expression in the Caco-2 cell line. Ten of these also inhibit expression of a reporter construct containing the CFTR 3′ UTR in one or more cell lines, and five repress endogenous CFTR protein expression in Caco-2 cells. Moreover, at least three are expressed in primary human airway epithelial cells, where CFTR expression is maintained at low levels in comparison with intestinal cell lines. Three of the miRNAs that target CFTR, hsa-miR-384, hsa-miR-494 and hsa-miR-1246, also inhibit expression of a reporter carrying the Na+–K+–Cl− co-transporter SLC12A2 [solute carrier family 12 (Na+–K+–Cl− transporters), member 2] 3′ UTR, suggesting that these miRNAs may play a more general role in regulating chloride transport in epithelial cells.
Molecular diversity of theTrypanosoma cruziTcSMUG family of mucin genes and proteins
Authors: Urban Ivana , Boiani Santurio Lucía , Chidichimo Agustina , Yu Hai , Chen Xi , Mucci Juan , Agüero Fernán , Buscaglia Carlos A.
Published: July 2011

The surface of the protozoan Trypanosoma cruzi is covered by a dense coat of mucin-type glycoconjugates, which make a pivotal contribution to parasite protection and host immune evasion. Their importance is further underscored by the presence of >1000 mucin-like genes in the parasite genome. In the present study we demonstrate that one such group of genes, termed TcSMUG L, codes for previously unrecognized mucin-type glycoconjugates anchored to and secreted from the surface of insect-dwelling epimastigotes. These features are supported by the in vivo tracing and characterization of endogenous TcSMUG L products and recombinant tagged molecules expressed by transfected parasites. Besides displaying substantial homology to TcSMUG S products, which provide the scaffold for the major Gp35/50 mucins also present in insect-dwelling stages of the T. cruzi lifecycle, TcSMUG L products display unique structural and functional features, including being completely refractory to sialylation by parasite trans-sialidases. Although quantitative real time-PCR and gene sequencing analyses indicate a high degree of genomic conservation across the T. cruzi species, TcSMUG L product expression and processing is quite variable among different parasite isolates.
Redox properties of the tissue factor Cys186–Cys209 disulfide bond
Authors: Liang Hai Po Helena , Brophy Teresa M. , Hogg Philip J.
Published: July 2011

TF (tissue factor) is a transmembrane cofactor that initiates blood coagulation in mammals by binding Factor VIIa to activate Factors X and IX. The cofactor can reside in a cryptic configuration on primary cells and de-encryption may involve a redox change in the C-terminal domain Cys186–Cys209 disulfide bond. The redox potential of the bond, the spacing of the reduced cysteine thiols and their oxidation by TF activators was investigated to test the involvement of the dithiol/disulfide in TF activation. A standard redox potential of −278 mV was determined for the Cys186–Cys209 disulfide of recombinant soluble TF. Notably, ablating the N-terminal domain Cys49–Cys57 disulfide markedly increased the redox potential of the Cys186–Cys209 bond, suggesting that the N-terminal bond may be involved in the regulation of redox activity at the C-terminal bond. Using As(III) and dibromobimane as molecular rulers for closely spaced sulfur atoms, the reduced Cys186 and Cys209 sulfurs were found to be within 3–6 Å (1 Å=0.1 nm) of each other, which is close enough to reform the disulfide bond. HgCl2 is a very efficient activator of cellular TF and activating concentrations of HgCl2-mediated oxidation of the reduced Cys186 and Cys209 thiols of soluble TF. Moreover, PAO (phenylarsonous acid), which cross-links two cysteine thiols that are in close proximity, and MMTS (methyl methanethiolsulfonate), at concentrations where it oxidizes closely spaced cysteine residues to a cystine residue, were efficient activators of cellular TF. These findings further support a role for Cys186 and Cys209 in TF activation.
Discovery of cellular substrates for protein kinase A using a peptide array screening protocol
Authors: Smith F. Donelson , Samelson Bret K. , Scott John D.
Published: July 2011

Post-translational modification of proteins is a universal form of cellular regulation. Phosphorylation on serine, threonine, tyrosine or histidine residues by protein kinases is the most widespread and versatile form of covalent modification. Resultant changes in activity, localization or stability of phosphoproteins drives cellular events. MS and bioinformatic analyses estimate that ~30% of intracellular proteins are phosphorylated at any given time. Multiple approaches have been developed to systematically define targets of protein kinases; however, it is likely that we have yet to catalogue the full complement of the phosphoproteome. The amino acids that surround a phosphoacceptor site are substrate determinants for protein kinases. For example, basophilic enzymes such as PKA (protein kinase A), protein kinase C and calmodulin-dependent kinases recognize basic side chains preceding the target serine or threonine residues. In the present paper we describe a strategy using peptide arrays and motif-specific antibodies to identify and characterize previously unrecognized substrate sequences for protein kinase A. We found that the protein kinases PKD (protein kinase D) and MARK3 [MAP (microtubule-associated protein)-regulating kinase 3] can both be phosphorylated by PKA. Furthermore, we show that the adapter protein RIL [a product of PDLIM4 (PDZ and LIM domain protein 4)] is a PKA substrate that is phosphorylated on Ser119 inside cells and that this mode of regulation may control its ability to affect cell growth.
Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism
Authors: Wang Bing , Peng Yingjie , Zhang Tianlong , Ding Jianping
Published: July 2011

GSTs (glutathione transferases) are a family of enzymes that primarily catalyse nucleophilic addition of the thiol of GSH (reduced glutathione) to a variety of hydrophobic electrophiles in the cellular detoxification of cytotoxic and genotoxic compounds. GSTks (Kappa class GSTs) are a distinct class because of their unique cellular localization, function and structure. In the present paper we report the crystal structures of hGSTk (human GSTk) in apo-form and in complex with GTX (S-hexylglutathione) and steady-state kinetic studies, revealing insights into the catalytic mechanism of hGSTk and other GSTks. Substrate binding induces a conformational change of the active site from an ‘open’ conformation in the apo-form to a ‘closed’ conformation in the GTX-bound complex, facilitating formations of the G site (GSH-binding site) and the H site (hydrophobic substrate-binding site). The conserved Ser16 at the G site functions as the catalytic residue in the deprotonation of the thiol group and the conserved Asp69, Ser200, Asp201 and Arg202 form a network of interactions with γ-glutamyl carboxylate to stabilize the thiolate anion. The H site is a large hydrophobic pocket with conformational flexibility to allow the binding of different hydrophobic substrates. The kinetic mechanism of hGSTk conforms to a rapid equilibrium random sequential Bi Bi model.
SLC41A1 Mg2+ transport is regulated via Mg2+-dependent endosomal recycling through its N-terminal cytoplasmic domain
Authors: Mandt Tyler , Song Yumei , Scharenberg Andrew M. , Sahni Jaya
Published: July 2011

SLC41A1 (solute carrier family 41, member A1) is a recently described vertebrate member of the MgtE family of Mg2+ transporters. Although MgtE transporters are found in both prokaryotic and eukaryotic organisms, and are highly conserved, little is known about the regulation of their Mg2+ transport function. In the present study, we have shown that endogenous SLC41A1 transporter expression is post-transcriptionally regulated by extracellular Mg2+ in TRPM7 (transient receptor potential cation channel, subfamily M, member 7)-deficient cells, suggesting that SLC41A1 transporters underlie a novel plasma membrane Mg2+ transport function. Consistent with this conclusion, structure–function analyses of heterologous SLC41A1 transporter expression demonstrate that SLC41A1 transporters exhibit the same plasma membrane orientation as homologous bacterial MgtE proteins, are capable of complementing growth of TRPM7-deficient cells only when the Mg2+ transporting pore is intact, and require an N-terminal cytoplasmic domain for Mg2+-dependent regulation of lysosomal degradation and surface expression. Taken together, our results indicate that SLC41A1 proteins are a central component of vertebrate Mg2+ transport systems, and that their Mg2+ transport function is regulated primarily through an endosomal recycling mechanism involving the SLC41A1 N-terminal cytoplasmic domain.
The structural plasticity of the human copper chaperone for SOD1: insights from combined size-exclusion chromatographic and solution X-ray scattering studies
Authors: Wright Gareth S. A. , Hasnain S. Samar , Grossmann J. Günter
Published: July 2011

The incorporation of copper into biological macromolecules such as SOD1 (Cu,Zn superoxide dismutase) is essential for the viability of most organisms. However, copper is toxic and therefore the intracellular free copper concentration is kept to an absolute minimum. Several proteins, termed metallochaperones, are charged with the responsibility of delivering copper from membrane transporters to its intracellular destination. The CCS (copper chaperone for SOD1) is the major pathway for SOD1 copper loading. We have determined the first solution structure of hCCS (human CCS) by SAXS (small-angle X-ray scattering) in conjunction with SEC (size-exclusion chromatography). The findings of the present study highlight the importance of this combined on-line chromatographic technology with SAXS, which has allowed us to unambiguously separate the hCCS dimer from other oligomeric and non-physiological aggregated states that would otherwise adversely effect measurements performed on bulk solutions. The present study exposes the dynamic molecular conformation of this multi-domain chaperone in solution. The metal-binding domains known to be responsible for the conveyance of copper to SOD1 can be found in positions that would expedite this movement. Domains I and III of a single hCCS monomer are able to interact and can also move into positions that would facilitate initial copper binding and ultimately transfer to SOD1. Conversely, the interpretation of our solution studies is not compatible with an interaction between these domains and their counterparts in an hCCS dimer. Overall, the results of the present study reveal the plasticity of this multi-domain chaperone in solution and are consistent with an indispensable flexibility necessary for executing its dual functions of metal binding and transfer.
Metabolic modulation induced by oestradiol and DHT in immature rat Sertoli cells culturedin vitro
Authors: Rato Luís , Alves Marco G. , Socorro Sílvia , Carvalho Rui A. , Cavaco José E. , Oliveira Pedro F.
Published: July 2011

Sertoli cells actively metabolize glucose that is converted into lactate, which is used by developing germ cells for their energy metabolism. Androgens and oestrogens have general metabolic roles that reach far beyond reproductive processes. Hence, the main purpose of this study was to examine the effect of sex hormones on metabolite secretion/consumption in primary cultures of rat Sertoli cells. Sertoli cell-enriched cultures were maintained in a defined medium for 50 h. Glucose and pyruvate consumption, and lactate and alanine secretion were determined, by 1H-NMR (proton NMR) spectra analysis, in the presence or absence of 100 nM E2 (17β-oestradiol) or 100 nM 5α-DHT (dihydrotestosterone). Cells cultured in the absence (control) or presence of E2 consumed the same amount of glucose (29±2 pmol/cell) at similar rates during the 50 h. After 25 h of treatment with DHT, glucose consumption and glucose consumption rate significantly increased. Control and E2-treated cells secreted similar amounts of lactate during the 50 h, while the amount of lactate secreted by DHT-treated cells was significantly lower. Such a decrease was concomitant with a significant decrease in LDH A [LDH (lactate dehydrogenase) chain A] and MCT4 [MCT (monocarboxylate transporter) isoform 4] mRNA levels after 50 h treatment in hormonally treated groups, being more pronounced in DHT-treated groups. Finally, alanine production was significantly increased in E2-treated cells after 25 h treatment, which indicated a lower redox/higher oxidative state for the cells in those conditions. Together, these results support the existence of a relation between sex hormones action and energy metabolism, providing an important assessment of androgens and oestrogens as metabolic modulators in rat Sertoli cells.
Requirement for store-operated calcium entry in sodium butyrate-induced apoptosis in human colon cancer cells
Authors: Sun Suxia , Li Wenjun , Zhang He , Zha Longying , Xue Yong , Wu Xianbo , Zou Fei
Published: July 2011

The SOCE (store-operated Ca2+ entry) pathway plays a key role in both normal cells and cancerous cells. However, its molecular mechanism remains a long-lasting puzzle of Ca2+ signalling. In this paper, we provide evidence that butyric acid, a dietary fibre-derived short-chain fatty acid, induces apoptosis of colon cancer cells via SOCE signalling networks. We found that sodium butyrate (NaB) induces Ca2+ release from endoplasmic reticulum, which in turn causes extracellular Ca2+ influx in HCT-116 cells. The Ca2+ release and influx are important, because the addition of chelators, EGTA or BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid tetrakis(acetoxymethyl ester)] respectively blocked NaB-induced apoptosis. Furthermore, down-regulation of STIM1 (stromal interaction molecule 1) by RNA interference or pharmacological blockade of the SOCC (store-operated Ca2+ channel) by 2-APB (2-aminoethoxydiphenyl borate) or SKF-96365 inhibited NaB-induced extracellular Ca2+ influx and apoptosis in HCT-116 cells. Thus we conclude that NaB triggers colon cancer cell apoptosis in an SOCE-dependent manner. This finding provides new insights into how butyric acid suppresses colon carcinogenesis.
ECM remodelling components regulated during jaw periosteal cell osteogenesis
Authors: Alexander Dorothea , Ardjomandi Nina , Munz Adelheid , Friedrich Björn , Reinert Siegmar
Published: July 2011

Human JPCs (jaw periosteal cells) are a promising source for the engineering of cell‐based osteoinductive grafts in oral surgery. For this purpose, cell characteristics of this stem cell source should be elucidated in detail. Analysis of gene expression profiles may help us to evaluate key factors and cellular targets of JPC osteogenesis. Because little is known about the interplay of osteogenic‐related components, we analysed the expression of different collagen types reflecting important players for extracellular matrix assembly and of TIMPs (tissue inhibitors of metalloproteinases) responsible for the inhibition of matrix degradation. Gene expression analyses using microarrays and quantitative RT—PCR (reverse transcription—PCR) during JPC osteogenesis revealed the induction of several collagen types' expression (VII, VIII, XI and XII), and some of them (types I, VIII and XI) seemed to be susceptible to BMP‐2 (bone morphogenetic protein‐2) that is known to be a potent osteogenic inducer of periosteal cells. Among the TIMPs, only TIMP‐4 and RECK (reversion‐inducing cysteine‐rich protein with Kazal motifs) expressions were strongly up‐regulated during JPC osteogenesis. Proteome profiler analysis of supernatants from untreated and differentiated JPCs confirmed the gene expression data in terms of TIMP expression. In summary, we identified new collagen types and TIMPs that seem to play important roles during the osteogenesis of jaw periosteal progenitor cells.
Delayed caspase‐8 activation and enhanced integrin β1‐activated FAK underpins anoikis in oesophageal carcinoma cells harbouring mt p53‐R175H
Authors: Fanucchi Stephanie , Veale Robin B
Published: July 2011

FAK (focal adhesion kinase)‐mediated signalling reportedly suppresses caspase‐8 activation and, as a consequence, rescues epithelial cells from Fas‐mediated anoikis. Critical was the use of a HOSCC (human oesophageal squamous carcinoma) cell line harbouring mt (mutant) p53‐R175H and displaying resistance to detachment and Tyr397 dephosphorylation of FAK. Here we show, although caspase‐8 activation is delayed in the mt p53‐R175H cell line, comparable apoptotic events evidenced in the wt (wild type) p53 HOSCC cell lines could be induced in the mt p53‐R175H cell line by strengthening the apoptotic stimulus. Significant to anoikis‐related regulation, the delay in caspase‐8 activation was accompanied by the maintenance of FAK Tyr397 phosphorylation, integrin β1‐associated FAK and a FAK/caspase‐8 complex. Thus, mt p53‐R175H may desensitize tumours to Fas‐mediated anchorage‐independent death via a FAK‐dependent mechanism.
Dissection of carotid sinus hypersensitivity: the timing of vagal and vasodepressor effects and the effect of body position
Authors: Krediet C. T. Paul , Jardine David L. , Wieling Wouter
Published: July 2011

We assessed the timing of vagal and sympathetic factors that mediate hypotension during CSM (carotid sinus massage) in patients with carotid sinus hypersensitivity. We hypothesized that a fall in cardiac output would precede vasodepression, and that vasodepression would be exaggerated by head-up tilt. We performed pulse contour analyses on blood pressure recordings during CSM in syncope patients during supine rest and head-up tilt. In a subset we simultaneously recorded muscle sympathetic nerve activity supine. During supine rest, systolic blood pressure decreased from 150±7 to 107±7 mmHg (P<0.001) and heart rate from 64±2 to 39±3 beats/min (P<0.01). Cardiac output decreased with heart rate to nadir (66±6% of baseline), 3.1±0.4 s after onset of bradycardia. In contrast, total peripheral resistance reached nadir (77±3% of baseline) after 11±1 s. During head-up-tilt, systolic blood pressure fell from 149±10 to 90±11 mmHg and heart rate decreased from 73±4 to 60±7 beats/min. Compared with supine rest, cardiac output nadir was lower (60±8 compared with 83±4%, P<0.05), whereas total peripheral resistance nadir was similar (81±6 compared with 80±3%). The time to nadir from the onset of bradycardia did not differ from supine rest. At the onset of bradycardia there was an immediate withdrawal of muscle-sympathetic nerve activity while total peripheral resistance decay occurred much later (6–8 s). The haemodynamic changes following CSM have a distinct temporal pattern that is characterized by an initial fall in cardiac output (driven by heart rate), followed by a later fall in total peripheral resistance, even though sympathetic withdrawal is immediate. This pattern is independent of body position.
Identification of diuretic non-responders with poor long-term clinical outcomes: a 1-year follow-up of 176 non-azotaemic cirrhotic patients with moderate ascites
Authors: Yang Ying-Ying , Lin Han-Chieh , Lin Ming-Wei , Chu Chi-Jen , Lee Fa-Yauh , Hou Ming-Chih , Lee Shou-Dong , Lee Wei-Ping , Liu Tze-Tze , Jap Tjin-Shing
Published: July 2011

In cirrhosis, the development of ascites and the response to diuretics are determined by the RAAS (renin–angiotensin–aldosterone system) and renal sodium handling system. We hypothesized that SNPs (single nucleotide polymorphisms) affecting candidate genes in the RAAS and renal sodium handling pathway may influence initial diuretic responsiveness and affect clinical outcome in non-azotaemic cirrhotic patients with moderate ascites. We prospectively recruited 176 patients and 245 controls and determined their genetic polymorphisms for 24 SNPs of ten genes involved in the RAAS and renal sodium handling pathway. In cirrhotic patients with moderate ascites, multivariate analysis showed that diuretic unresponsiveness was predicted by a high basal plasma aldosterone level, by a high aldosterone/renin ratio and by specific risk genotypes of ACE (gene encoding angiotensin-converting enzyme), CYP11B2 (gene encoding aldosterone synthase) and ADDA (gene encoding α-adducin). This association between genetic polymorphisms and diuretic unresponsiveness was confirmed by an independent validation cohort. Notably, additive effects in relation to diuretic unresponsiveness were observed in cases where there was the simultaneous presence of the three risk genotypes. Among patients carrying any of the risk genotypes, more episodes of paracentesis and ascites-related readmission after 3 months of treatment, as well as a reduced 1-year survival rate, were observed. In addition to traditional predictors, our present study provides additional genetic and neurohormonal predictors that will help to identify diuretic non-responders among cirrhotic patients with moderate ascites. Among those carrying unfavourable risk genotypes, additional therapies, including paracentesis and albumin infusion, should be started as early as possible.
The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma
Authors: Zhang Tengfei , Wang Qiming , Zhao Dan , Cui Yaling , Cao Bangrong , Guo Liping , Lu Shih Hsin
Published: July 2011

miR-31 (microRNA-31) is frequently altered in numerous cancers. The aim of the present study was to investigate the role of miR-31 in ESCC (oesophageal squamous cell carcinoma). We measured miR-31 in 45 paired ESCC tissues and 523 serum samples using real-time RT (reverse transcription)–PCR. The serum samples were divided into a discovery group (120 ESCCs and 121 normal controls), a validation group (81 ESCCs and 81 controls), and a final group comprising six other common tumours (colorectal, liver, cervical, breast, gastric and lung cancers; total n=120). A Mann–Whitney U test and Wilcoxon matched-pairs test were used for the statistics. miR-31 was up-regulated in 77.8% of the ESCC tissues. Serum miR-31 levels in ESCC patients were significantly higher than in normal controls (P<0.001). It yielded an ROC (receiver operating characteristic) AUC (area under the curve) of 0.902 [95% CI (confidence interval), 0.857–0.936] in the discovery group and a similar result in the validation group [ROC AUC, 0.888 (95% CI, 0.819–0.939)]. Patients with high-levels of serum miR-31 also had a poorer prognosis in relapse-free survival (P=0.001) and tumour-specific survival (P=0.005). In vitro studies showed that miR-31 promoted ESCC colony formation, migration and invasion. Luciferase reporter and Western blot assays confirmed that three tumour suppressor genes, namely EMP1 (epithelial membrane protein 1), KSR2 (kinase suppressor of ras 2) and RGS4 (regulator of G-protein signalling 4), were targeted by miR-31. We conclude that miR-31 plays oncogenetic functions and can serve as a potential diagnostic and prognostic biomarker for ESCC.
Large eddy simulation of the flow around single and two side-by-side cylinders at subcritical Reynolds numbers
Authors: Afgan I. , Kahil Y. , Benhamadouche S. , Sagaut P.
Published: July 2011

The flow around single and two side-by-side infinite cylinders is numerically modelled using dynamic Smagorinsky large eddy simulation (LES). For the single cylinder, the Reynolds number based on the diameter and the free stream velocity is 3900. A complete sensitivity study was conducted based on the extrusion length in the span-wise direction, the grid refinement at the wall, the convection scheme, and the sub-grid scale (SGS) model. It was found that the mean solution is not influenced by the extrusion length beyond 4 diameters or by 1% up-winding. However, coarsening the mesh in the wall normal direction or switching off the sub-grid scale model led to drastic effects on the recirculation length and on the underlying velocity field. The two side-by-side cylinders were tested for a range of pitch to diameter ratios (T/D=1.0,1.25≤T/D≤5.0) at a Reynolds number of 3000. For the intermediate pitch to diameter ratios (1.25≤T/D≤1.75), multiple shedding frequencies were detected with a biased wake flow deflection. Furthermore, this biased flow deflection was found to be bistable, i.e., it changes the direction (flipping over) intermittently from one side to the other. This behavior was found to be consistent with reported experimental measurements. During the flip-over from one stable mode to the other, the intermittent gap vortex shedding was found to be stronger than for a stable mode, with in-phase vortex shedding. However, for the higher pitch ratio cases (T/D≥2), a symmetrical wake behavior with anti-phase vortex shedding was observed.
Photoluminescence responses of Si nanocrystal to differing pumping conditions
Authors: Zhu Jiang , Wu Xiang , Zhang Miao , Wang Yin , Ning Xi-Jing , Zhao You-Yuan , Lu Ming
Published: July 2011

Under a CW Ar+ laser beam excitation with wavelength of 496 nm, the relationship of photoluminescence (PL) intensity versus pumping power density was investigated for both multilayered Si nanocrystal doped SiO2/SiO2 sample (or Si-nc:SiO2/SiO2) and single-layered Si-nc:SiO2 one. The threshold of pump power density for the transition from linear to superlinear relation of PL intensity versus pump power was ∼ 86 W cm−2 for the multilayered sample, while such a transition was not found for the single-layered one that possessed the same excess Si content within the power density range of this work. Using a pulsed Ti:sapphire laser (wavelength = 400 nm), a net optical gain coefficient was measured by means of variable slit length for the multilayered sample, which was 114 cm−1 at the pump fluence of 200 mJ cm−2, but only optical absorption was found for the single-layered sample. We attributed our results to the relatively high PL efficiency of the multilayered Si-nc:SiO2/SiO2.
Experimental measurements of the heats of formation of Fe3Pt, FePt, and FePt3 using differential scanning calorimetry
Authors: Wang B. , Berry D. C. , Chiari Y. , Barmak K.
Published: July 2011

Using differential scanning calorimetry (DSC), the heats of formation of Fe3Pt, FePt, and FePt3 were determined from the reaction of sputter deposited Fe/Pt multilayer thin-films with a periodicity of 200 nm but different overall compositions. Film compositions were measured by energy dispersive x-ray spectrometry. The phases present along the reaction path were identified by x-ray diffraction. For the most Fe-rich phase, namely, Fe3Pt, the measured enthalpy of formation was −9.3 ± 1.3 kJ/mol in a film with a composition of 70.4:29.6 (±0.2 at. %) Fe:Pt. For FePt, the measured enthalpy of formation was −27.2 ± 2.2 kJ/g-atom in a 49.0:51.0 (±0.5 at. %) Fe:Pt film. For FePt3, which is the most Pt rich intermetallic phase, the measured enthalpy of formation was −23.7 ± 2.2 in a film with a composition of 22.2:77.8 (±0.6 at. %) Fe:Pt. The reaction enthalpies for films with Fe:Pt compositions of 44.5:55.5 (±0.3 at. %) and 38.5:61.5 (±0.4 at. %) were −26.9 ± 1.0 and −26.6 ± 0.6 kJ/g-atom, respectively, which taken together with the value for the 49.0:51.0 film demonstrate the relative insensitivity of the reaction enthalpy to film composition over a broad composition range in the vicinity of the equiatomic composition. The experimental heats of formation are compared with two sets of reported first-principles calculated values for each of the three phases at exact stoichiometry.
Direct probing magnetization reversal of exchange-coupled-composite media by x-ray magnetic circular dichroism
Authors: Hou Hao-Cheng , Suess Dieter , Liao Jung-Wei , Lin Meng-Shian , Lin Hong-Ji , Chang Fan-Hsiu , Lai Chih-Huang
Published: July 2011

X-ray magnetic circular dichroism (XMCD) was used to directly probe the depth-dependent magnetization reversal of CoPtCr-SiO2-based exchange-coupled-composite media with laminated soft layers. A thin Fe-marker layer in the soft layer was used as the indicator of local magnetization. Element-specific XMCD loops of Fe-marker layers confirmed the transition of the magnetization reversal from rigid magnets to exchange-spring magnets with increasing thickness of the soft layer. The micromagnetic simulations revealed the importance of the reduced exchange constant (Asoft) by laminating the soft layer for domain-wall assisting reversal. By comparing XMCD loops with simulations, we can deduce the effective Asoft.
Electronic and magnetic properties of early transition-metal substituted iron-cyclopentadienyl sandwich molecular wires: Parity-dependent half-metallicity
Authors: Li Yuanchang , Zhou Gang , Wu Jian , Duan Wenhui
Published: July 2011

Electronic and magnetic properties of early transition metals (V, Ti, Sc)-FekCpk + 1 sandwich molecular wires (SMWs) are investigated by means of ab initio calculations. It is found that all SMWs favor a ferromagnetic ground state. Significantly, V-FekCpk + 1 SMWs are either half-metallic or semiconducting, dependent upon the parity (even or odd) of the number (k) of Fe atoms in the unit cell of SMWs. This parity oscillation of conductive properties results from the combined effects of the band-folding and gap-opening at the Brillouin-zone boundary of one-dimensional materials. In contrast, Sc-FekCpk + 1 and Ti-FekCpk + 1 SMWs are always semiconducting. Our work may open up the way toward half metal/semiconductor heterostructures with perfect atomic interface.
Resummed thermodynamic perturbation theory for central force associating potential. Multi-patch models
Authors: Kalyuzhnyi Y. V. , Docherty H. , Cummings P. T.
Published: July 2011

A resummed thermodynamic perturbation theory for associating fluids with multiply bondable central force associating potential is extended for the fluid with multiple number of multiply bondable associating sites. We consider a multi-patch hard-sphere model for associating fluids. The model is represented by the hard-sphere fluid system with several spherical attractive patches on the surface of each hard sphere. Resummation is carried out to account for blocking effects, i.e., when the bonding of a particle restricts (blocks) its ability to bond with other particles. Closed form analytical expressions for thermodynamical properties (Helmholtz free energy, pressure, internal energy, and chemical potential) of the models with arbitrary number of doubly bondable patches at all degrees of the blockage are presented. In the limiting case of total blockage, when the patches become only singly bondable, our theory reduces to Wertheim's thermodynamic perturbation theory (TPT) for polymerizing fluids. To validate the accuracy of the theory we compare to exact values, for the thermodynamical properties of the system, as determined by Monte Carlo computer simulations. In addition we compare the fraction of multiply bonded particles at different values of the density and temperature. In general, predictions of the present theory are in good agreement with values for the model calculated using Monte Carlo simulations, i.e., the accuracy of our theory in the case of the models with multiply bondable sites is similar to that of Wertheim's TPT in the case of the models with singly bondable sites.
Complete bandgap arising from the effects of hollow, veins, and intersecting veins in a square lattice of square dielectric rods photonic crystal
Authors: Ho Hong-Fa , Chau Yuan-Fong , Yeh Hsiao-Yu , Wu Fong-Lin
Published: July 2011

We perform numerical analysis of ultralarge complete photonic bandgap (CPBG) of two-dimensional photonic crystals, which are square arrays of dielectric-shell rods, with dielectric veins and intersecting veins to link them. It is shown how a maximum CPBG, Δω = 0.222592(2πc/a), is obtained within the fabrication tolerance by tuning the structural parameters. In addition, the effects on CPBG arising from the metamaterial are also discussed.
Tunable coupling between exciton and surface plasmon in liquid crystal devices consisting of Au nanoparticles and CdSe quantum dots
Authors: Chen Chung-Tse , Liu Chun-Chih , Wang Chun-Hsiung , Chen Chih-Wei , Chen Yang-Fang
Published: July 2011

We report controllable coupling between exciton and localized surface plasmon in a liquid crystal device consisting of gold nanoparticles and CdSe quantum dots. Through an external electric voltage, the emission wavelength of quantum dots can be manipulated. The underlying mechanism is based on the fact that by changing the dielectric index of liquid crystal with an external bias, the surface plasmon frequency of metal nanoparticles can be adjusted. It is therefore possible to control the energy difference between exciton and surface plasmon resonance, and hence to change their coupling strength. Our strategy may open up a possible route for the development of smart optoelectronic devices with tunable emission color.
Rare earth doped core-shell particles as phosphor for warm-white light-emitting diodes
Authors: Korthout K. , Smet P. F. , Poelman D.
Published: July 2011

Light-emitting diodes (LEDs) are efficient, energy-saving light sources. Unfortunately, designing phosphors for LEDs that emit warm white light is not straightforward. We solvothermally prepared rare earth doped alkaline earth sulfides with a core-shell structure in order to obtain a physical separation between different dopants (europium and cerium). Cathodoluminescence of a single phosphor particle in an electron microscope proves simultaneous Eu2+ and Ce3+ broad band emission. The emission color can be tuned by variation of the composition, core size, and shell thickness. Upon excitation of SrS:Eu2+-SrS:Ce3+ core-shell structures at 430 nm, white light emission with good color rendering and a color temperature around 3000 K is obtained.
Erratum: “Self-similar blowup solutions to the 2-component Camassa–Holm equations” [J. Math. Phys. 51, 093524 (2010)]
Authors: Yuen Manwai
Published: July 2011

Changes have been made to this article. See the full text for a description of the changes.
Note: Light ageing with simultaneous colorimetry via fibre optics reflection spectrometry
Authors: Łojewski Tomasz , Thomas Jacob , Gołąb Roman , Kawałko Jakub , Łojewska Joanna
Published: July 2011

In this article, the design and characteristics of a micro-fadeometer is presented. The technique allows for a non-(micro-) destructive evaluation of the light fastness of colorants on various materials and can be used to directly assess valuable materials, such as heritage objects, and develop safer display strategies to promote their preservation. The presented instrument has several benefits over standard light ageing methods – low operating cost, non-damaging, real time measurement of induced changes for kinetics studies, and automated high throughput screening of materials. A selection of data is presented to demonstrate the flexibility of the presented instrument and illustrate how it can be used to evaluate museum lighting and oxygen-free display of heritage objects.
Optical gain observation on silicon nanocrystals embedded in silicon nitride under femtosecond pumping
Authors: Monroy B. M. , Crégut O. , Gallart M. , Hönerlage B. , Gilliot P.
Published: July 2011

We report the observation of positive optical gain in silicon nanocrystals (Si-nc) embedded in silicon nitride measured by the variable stripe length technique. We evidence the onset of stimulated emission and report gain coefficients up to 52 cm−1 at the highest excitation power (6.5 W/cm2). Photoluminescence dynamics presents two distinct recombination lifetimes in the nanosecond and the microsecond ranges. This was interpreted in terms of fast carrier trapping in nitrogen-induced localized states in the Si-nc surface and subsequent slow radiative recombination, suggesting that carrier trapping in radiative surface states plays a crucial role in the optical gain mechanism of Si-nc.
Second harmonic generation in GaP photonic crystal waveguides
Authors: Rivoire Kelley , Buckley Sonia , Hatami Fariba , Vučković Jelena
Published: July 2011

We demonstrate enhanced second harmonic generation in a gallium phosphide photonic crystal waveguide with a measured external conversion efficiency of 5 × 10−7/W. Our results are promising for frequency conversion of on-chip integrated emitters having broad spectra or large inhomogeneous broadening, as well as for frequency conversion of ultrashort pulses.
Shale-gas extraction faces growing public and regulatory challenges
Authors: Kramer David
Published: July 2011

Two federal agencies are scrutinizing the shale-gas industry and its use of “fracking,” but gas producers insist that state regulators provide sufficient environmental oversight.
From near-field optics to optical antennas
Authors: Novotny Lukas
Published: July 2011

Nanoscale probes that convert light into localized energy or vice versa form the basis for diffraction-unlimited imaging and intriguing light–matter interactions.
Probability, physics, and the coin toss
Authors: Mahadevan L. , Yong Ee Hou
Published: July 2011

When you flip a coin to decide an issue, you assume that the coin will not land on its side and, perhaps less consciously, that the coin is flipped end over end. What happens if those assumptions are relaxed?
A Robotic Brain Scheme: Proposal Originated by a Modular Robotic Control
Authors: Negrete-Martínez J.
Published: July 2011

A robot brain scheme has been implemented, based on and controlled by analog circuits and micro‐controllers. The modules have been classified as: (a) world signal processing, (b) world signal relevance assessing, (c) pre‐motor decisions, (d) motor behavior, and (e) planning and sequencing motor behaviors. There are two types of pre‐motor processing: main and world signal tracking. Motor behavior includes all the final motion units. Each of these five classes roughly corresponds to areas in a vertebrate’s brain and proved to be an effective robotic brain scheme as they assist in the development of greater complexity in robotic brains and a means to compare different implementations. The scheme stresses the importance of motor behavior modules fed by pre‐motor decision modules. The pre‐motor decision modules aim the movement while the motor behavior module creates the behavior. Finally, the planning and sequencing modules are imperative implementations in a robotic brain.
A longitudinal phenomenological analysis of coping effectiveness among Scottish international adolescent golfers
Authors: Nicholls Adam R.
Published: July 2011

The aim of this study was to explore coping effectiveness among international golfers. Five Scottish international adolescent golfers (mean age 16.6 years, s = 0.6) maintained daily coping effectiveness diaries over a 28‐day period during their competitive season. Data were thematically analysed using interpretive phenomenological analysis (Smith & Osborn, 2003). The participants reported 56 effective coping strategies and 23 ineffective coping strategies. The unique finding from this study is that the same coping strategies were often rated as being both effective and ineffective, even when they were employed to manage the same stressor. This suggests that the goodness‐of‐fit approach and the choice of coping strategy theories may not be adequate explanations of coping effectiveness. Applied practitioners working with golfers are encouraged to teach their clients a variety of coping strategies, which should be deployed in combination.
A novel and simple technique for measuring low-loss materials using the two flanged waveguides measurement geometry*
Authors: Hyde M W , Havrilla M J , Bogle A E
Published: July 2011

In this paper, a novel technique is developed to practically and accurately measure the permittivity and permeability of low-loss materials using the two flanged waveguides measurement geometry (originally designed to characterize strongly absorbing materials only). A review of the two flanged waveguides measurement technique (tFWMT) as well as the Green's function-based flange-design criterion is provided. This review is followed by the introduction of the novel method (called tFWMT time-domain gating). It is shown that tFWMT time-domain gating extends the range of applicability of the tFWMT to low-loss materials and provides a clear flange-size design requirement which, for low-loss materials, is approximately two orders of magnitude smaller than that stipulated by the existing Green's function-based criterion. Lastly, material-characterization measurement results of low-loss acrylic and ECCOSORB® FGM-125, using flanges of two different sizes, are presented to validate the new technique.