bluuebunny/crossref_metadata_2025 huggingface dataset:
The duration of TCR/pMHC interactions regulates CTL effector function and tumor‐killing capacity
Authors: Riquelme Erick , Carreño Leandro J. , González Pablo A. , Kalergis Alexis M.
Published: July 2009

Effector CTL contribute to tumoral immunity by killing tumor cells through secretion of cytotoxic granules and cytokines. Activation of CTL requires specific recognition of cognate peptide‐MHC‐I (pMHC) complexes on the tumor cell surface by the CTL TCR. It has been suggested that the half‐life (t1/2) of the TCR/pMHC interaction modulates the activation of naïve CD8+ T cells; however, it remains unknown whether CTL effector function can also be regulated by the TCR/pMHC t1/2. Here, we have studied CTL activity in response to tumor cells loaded with pMHC that bind the TCR with different t1/2. We observed that the TCR/pMHC t1/2 can differentially regulate CTL effector function during the interaction with tumor cells and defines the nature of anti‐tumoral CTL responses in vivo. Although prolonged TCR/pMHC t1/2 promoted only partial expression of cytotoxic molecules, short t1/2 induced partial polarization of lytic machinery toward target cells. In contrast, intermediate TCR/pMHC t1/2 induced strong expression of cytotoxic molecules, efficient polarization of lytic machinery and subsequent release of toxic granules by CTL that killed tumor cells. Consistently, efficient in vivo CTL‐mediated tumor clearance was only observed for tumors expressing intermediate t1/2 pMHC ligands. These data suggest that there is an optimal TCR/pMHC t1/2 for efficient CTL activity.
Homeostatic proliferation and survival of naïve and memory T cells
Authors: Boyman Onur , Létourneau Sven , Krieg Carsten , Sprent Jonathan
Published: July 2009

The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady‐state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long‐term survival of memory cells. The reduction of T‐cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia‐induced proliferation and restoration of normal T‐cell levels. Such expansion is governed by the interaction of TCR with self‐peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL‐7. These same ligands, i.e. p/MHC molecules and IL‐7, maintain naïve T lymphocytes as resting cells under steady‐state T‐cell‐sufficient conditions. Unlike naïve cells, typical “central” memory T cells rely on a combination of IL‐7 and IL‐15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T‐cell subsets are less quiescent and include naturally occurring activated memory‐phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T‐cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.
Memory B cells: Effectors of long‐lived immune responses
Authors: Tangye Stuart G. , Tarlinton David M.
Published: July 2009

Immunological memory is the phenomenon whereby B and T cells have the unique ability to respond with heightened kinetics and efficacy to subsequent encounter with Ag relative to the initial exposure. In this review, we examine recent developments in the phenotypic characterisation of memory B cells, with an emphasis on the definition and functional properties of memory B‐cell subsets in humans. Gene expression differences are also considered in light of the unique functional and survival properties of memory B cells, and mutations that alter memory formation and function are also examined. Finally, we consider recent advances in the understanding of germinal center B‐cell differentiation through analysis of transcription factor networks operating in these B cells.
Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4+ T‐cell‐independent CD8+ T‐cell‐mediated tumor control
Authors: Sorensen Maria R. , Holst Peter J. , Pircher Hanspeter , Christensen Jan P. , Thomsen Allan R.
Published: July 2009

Antigen‐specific immunotherapy is an attractive strategy for cancer control. In the context of antiviral vaccines, adenoviral vectors have emerged as a favorable means for immunization. Therefore, we chose a strategy combining use of these vectors with another successful approach, namely linkage of the vaccine antigen to invariant chain (Ii). To evaluate this strategy we used a mouse model, in which an immunodominant epitope (GP33) of the LCMV glycoprotein (GP) represents the tumor‐associated neoantigen. Prophylactic vaccination of C57BL/6 mice with a replication‐deficient human adenovirus 5 vector encoding GP linked to Ii (Ad‐Ii‐GP) resulted in complete protection against GP33‐expressing B16.F10 tumors. Therapeutic vaccination with Ad‐Ii‐GP delayed tumor growth by more than 2 wk compared with sham vaccination. Notably, therapeutic vaccination with the linked vaccine was significantly better than vaccination with adenovirus expressing GP alone (Ad‐GP), or GP and Ii unlinked (Ad‐GP+Ii). Ad‐Ii‐GP‐ induced tumor control depended on an improved generation of the tumor‐associated neoantigen‐specific CD8+ T‐cell response and was independent of CD4+ T cells. IFN‐γ was shown to be a key player during the tumor degradation. Finally, Ad‐Ii‐GP but not Ad‐GP vaccination can break the immunological non‐reactivity in GP transgenic mice indicating that our vaccine strategy will prove efficient also against endogenous tumor antigens.
Generating memory with vaccination
Authors: Castellino Flora , Galli Grazia , Del Giudice Giuseppe , Rappuoli Rino
Published: July 2009

The goal of vaccination is to induce long‐lasting protective immune memory. Although most vaccines induce good memory responses, the type of memory induced by different vaccines may be considerably different. In addition, memory responses to the same vaccine may be influenced by age, environmental and genetic factors. Results emerging from detailed and integrated profiling of immune‐responses to natural infection or vaccination suggest that the type and duration of immune memory are largely determined by the magnitude and complexity of innate immune signals that imprint the acquired immune primary responses. Here we summarize results obtained from analyzing human immune memory responses to different types of vaccines. We will also discuss how extending clinical investigation to events occurring early after vaccination can help identify early predictive markers of protective memory and thus contribute to faster development of better and safer vaccines.
Making and circumventing tolerance to cancer
Authors: Kammertoens Thomas , Blankenstein Thomas
Published: July 2009

The interactions between cancer and immune cells are complex. Even though the mutations that cause cancer can create new antigens that are potentially “visible” to T cells, in most experimental model systems the growth of tumors is accompanied by induction of T‐cell tolerance towards the tumor. How tolerance to tumors is induced and how tolerance can be broken by immunotherapy have been a main focus in cancer immunology. Here, we discuss experimental models used in cancer immunology. We argue that, while it is obviously easy for tumors to induce tolerance, it should be as easy to circumvent tolerance by the adoptive transfer of tumor‐antigen‐reactive T cells. Effective adoptive T‐cell therapy has become feasible by methods to identify TCR against tumor‐associated (self‐) antigens with high affinity and to graft a new antigen specificity to patients' T cells by TCR gene transfer.
TLR2 engagement on memory CD8+ T cells improves their cytokine‐mediated proliferation and IFN‐γ secretion in the absence of Ag
Authors: Cottalorda Anne , Mercier Blandine C. , Mbitikon‐Kobo Florentin M. , Arpin Christophe , Teoh Denise Y. L. , McMichael Andrew , Marvel Jacqueline , Bonnefoy‐Bérard Nathalie
Published: July 2009

Persistence of memory CD8+ T cells is known to be largely controlled by common gamma chain cytokines, such as IL‐2, IL‐7 and IL‐15. However, other molecules may be involved in this phenomenon. We show here that TLR2−/− mice have a decreased frequency of memory phenotype CD8+ T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8+ T cells. We describe here a new TLR2‐dependent mechanism which, in the absence of specific antigen, directly controls memory CD8+ T‐cell proliferation and IFN‐γ secretion. We demonstrate that TLR2 engagement on memory CD8+ T cells increases their proliferation and expansion induced by IL‐7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL‐2 to induce IFN‐γ secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen‐specific memory CD8+ T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8+ T cells in the organism.
Development and maturation of invariant NKT cells in the presence of lysosomal engulfment
Authors: Plati Tiziana , Visigalli Ilaria , Capotondo Alessia , Buono Mario , Naldini Luigi , Cosma Maria Pia , Biffi Alessandra
Published: July 2009

A defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T‐cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection.
Diverse regulatory roles for lysosomal proteases in the immune response
Authors: Colbert Jeff D. , Matthews Stephen P. , Miller Gail , Watts Colin
Published: July 2009

The innate and adaptive immune system utilise endocytic protease activity to promote functional immune responses. Cysteine and aspartic proteases (cathepsins) constitute a subset of endocytic proteases, the immune function of which has been described extensively. Although historically these studies have focused on their role in processes such as antigen presentation and zymogen processing within the endocytic compartment, recent discoveries have demonstrated a critical role for these proteases in other intracellular compartments, and within the extracellular milieu. It has also become clear that their pattern of expression and substrate specificities are more diverse than was first envisaged. Here, we discuss recent advances addressing the role of lysosomal proteases in various aspects of the immune response. We pay attention to reports demonstrating cathepsin activity outside of its canonical endosome/lysosome microenvironment.
Triphenylamine‐Based Pyridine N‐Oxide and Pyridinium Salts for Size‐Selective Recognition of Dicarboxylates
Authors: Ghosh Kumaresh , Masanta Goutam , Chattopadhyay Asoke P.
Published: July 2009

Triphenylamine‐based receptors 1–3 have been designed and synthesized for the recognition of dicarboxylates. The correct dispositions of the binding groups in both 1 and 2 under 4,4′‐dicarbonyltriphenylamine spacer enable them to bind aliphatic dicarboxylates of different chain lengths with moderate binding constant values. In the binding event, triphenylamine‐based pyridinium salt 2 is found to be more effective than triphenylamine‐based pyridine N‐oxide 1 and shows selectivity for long‐chain pimelate. Binding takes place at charged sites with concomitant PET‐based (photo‐induced electron transfer) quenching of emission of triphenylamine motif. The binding was monitored in DMSO using 1H NMR, UV/Vis and fluorescence spectroscopic methods. Efficiency of pyridinium binding site over the others in the present study has been rationalised by invoking theoretical results. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Stereoselective Synthesis of New Ferrocene‐Derived Amino Acid Building Blocks
Authors: Hunold Andrea , Neundorf Ines , James Philippe , Neudörfl Jörg , Schmalz Hans‐Günther
Published: July 2009

As a contribution to bioorganometallic chemistry, a dia‐ and enantioselective synthesis of novel carbocyclic amino acid analogues with a 1,2‐ferroceno‐fused cyclopentene backbone has been developed. Using two related planar‐chiral intermediates, i.e. (1S,E)‐ethyl‐3‐[2‐(phenylsulfonylacetyl)ferrocen‐1‐yl]acrylate, (1S,E)‐ethyl‐3‐[2‐(methoxycarbonyl)ferrocen‐1‐yl]acrylate, stereoselective entries to different tBoc‐ or Fmoc‐protected ferroceno‐fused 1‐amino‐3‐carboxyalkyl‐2‐cyclopentenes were elaborated. These compounds were then used for the preparation of metal‐containing peptides by means of solid‐phase peptide synthesis (SPPS). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Bismalonates Constructed on a Hexaphenylbenzene Scaffold for the Synthesis of Equatorial Fullerene Bisadducts (Eur. J. Org. Chem. 23/2009)
Authors: Figueira‐Duarte Teresa M. , Gégout Aline , Olivier Jean , Cardinali François , Nierengarten Jean‐François
Published: July 2009

The cover picture shows a sun‐shaped hexaphenylbenzene unit shining over the equator of a fullerene spheroid. This macrocyclic fullerene bisadduct with an equatorial addition pattern was obtained with excellent regioselectivity from the reaction of C60 with a bismalonate constructed on a hexaphenylbenzene scaffold. Details are discussed in the article by J.‐F. Nierengarten et al. on p. 3879 ff.
Differentiation of green tea samples by chiral CD‐MEKC analysis of catechins content
Authors: Gotti Roberto , Furlanetto Sandra , Lanteri Silvia , Olmo Stefano , Ragaini Alessandro , Cavrini Vanni
Published: July 2009

A chiral CD‐MEKC method, enantioselective for catechin and gallocatechin, was developed, validated and applied to the analysis of tea samples. The method was addressed to the fast and simultaneous quantitation of the most represented and biologically important green tea catechins and methylxanthines. The CD‐MEKC was based on SDS as surfactant (90 mM) and hydroxypropyl‐β‐CD (25 mM) as chiral selector, under acidic conditions (25 mM borate–phosphate buffer, pH 2.5). The method was first applied to study the thermal epimerisation of epi‐structured catechins, (−)‐epicatechin and (−)‐epigallocatechin, to non‐epi‐structured (−)‐catechin and (−)‐gallocatechin. The latter compounds, being non‐native molecules, were for the first time regarded as useful phytomarkers of tea samples subjected to thermal treatment. The proposed method was applied to the analysis of more than twenty tea samples of different geographical origins (China, Japan, Ceylon), having undergone different storage conditions and manufacturing processes. Finally, factor analysis was used to visualise the useful information contained in the data set, showing that it was possible to distinguish tea samples on the basis of their different contents of native and non‐native catechins.
Enantioseparation by MEKC using a ligand exchange‐based chiral pseudostationary phase
Authors: Zaher Mustapha , Ravelet Corinne , Vanhaverbeke Cecile , Baussanne Isabelle , Perrier Sandrine , Fize Jennifer , Décout Jean‐Luc , Peyrin Eric
Published: July 2009

In this paper, a new ligand‐exchange ‐MEKC mode, based on the design of a unique lipohilic species (4′‐octadecylneamine derivative), which served both as micelle‐forming surfactant (by its hydrophobic part) and central ion‐complexing ligand (by its hydrophilic part) is described. The CMC of the used lipophilic neamine derivative was first determined by surface tension measurements. Subsequent NMR experiments were performed in order to investigate the Cu(II) binding properties of the neamine micellar phase. The enantioseparation properties of both the octadecylneamine derivative‐Cu(II) MEKC and the native neamine‐Cu(II) CE systems were evaluated and compared using the tryptophan racemate as a probe analyte. The effects of several different electrophoretic conditions on the enantiomer migration behavior in the ligand‐exchange‐MEKC mode were examined. The developed methodology was also applied to the enantioseparation of other analytes such as 1‐methyl‐tryptophan, 3,5‐diiodo‐tyrosine and 1‐naphtyl‐alanine.
Transient ζ‐potential measurements in hydrophobic, TOPAS microfluidic substrates
Authors: Tandon Vishal , Bhagavatula Sharath K. , Kirby Brian J.
Published: July 2009

We utilize time‐resolved electrokinetic measurements in order to study the electrokinetic properties of silica and TOPAS microfluidic channels as a function of the time history of the fluid–solid interface. In pressure‐driven flow through TOPAS microchannels, the ζ‐potential as inferred from streaming potential measurements decays exponentially by a factor of 1.5 with a characteristic decay time of 3 h after the initial formation of the fluid–solid interface. A similar exponential decay is observed immediately after water is exchanged for ethanol as the solvent in the system. In electroosmotically driven flow through TOPAS microchannels, the ζ‐potential as inferred through current monitoring experiments was constant in time. No electrokinetic transients were observed in silica microchannels under these flow conditions.
Determination of cyanobacterial cyclic peptide hepatotoxins in drinking water using CE
Authors: Birungi Grace , Yau Li Sam Fong
Published: July 2009

Four cyanobacteria hepatotoxins microcystin LR, microcystin RR, microcystin YR, and nodularin were simultaneously determined in drinking water using CZE and MEKC coupled with UV detection. The toxins were satisfactorily separated in both CZE and MEKC modes. Detection limits were in the range of 0.82–4.81 μg/mL, with R2 values of 0.994–0.999. The linearity range tested for the standards was 5–100 μg/mL and RSD percentages were in the range of 1.0–2.5% for retention time and 3.0–10.2% for peak area. When a known amount of standard was spiked into a known volume of water and extracted, recoveries were 90.3% (RR), 101.5% (nodularin), 90.6% (YR), and 88.2% (LR). The use of SPE enabled cleanup and pre‐concentration of a real sample to achieve a 100‐fold concentration factor. Detection limits after SPE of the real sample spiked with microcystins were 0.090 μg/L (RR), 0.076 μg/L (YR), and 0.110 μg/L (LR), with RSD percentage values of 9.9–11.7% for peak area and 2.2–3.3% for retention time. The technique developed provides an alternative method for determining microcystins at levels of concentration that will be able to meet WHO drinking water guidelines for microcystins.
Genetic characterization of Cryptosporidium parvum from calves by mutation scanning and targeted sequencing – zoonotic implications
Authors: Nolan Matthew J. , Jex Aaron R. , Mansell Peter D. , Browning Glenn F. , Gasser Robin B.
Published: July 2009

This study explored the genetic make‐up of Cryptosporidium in fecal samples from 268 individual calves on pasture‐based dairy farms in three regions of Victoria, Australia. An integrated approach, using PCR‐coupled single‐strand conformation polymorphism, targeted sequencing and phylogenetic analysis, was employed to classify the genetic variants (i.e. genotypes and subgenotypes) of Cryptosporidium parvum present in 124 (46.3%) samples and to infer their zoonotic potential. Genotypic and subgenotypic classification was achieved using a portion of the 60 kDa glycoprotein gene (designated pgp60); specific identity was verified using a region within the small subunit of the nuclear ribosomal RNA (pSSU). Twelve sequence types representing ten distinct subgenotypes were defined within genotype IIa, namely IIaA16G3R1 (n=7), IIaA17G2R1 (1), IIaA18G2R1a (2), IIaA18G2R1b (1), IIaA18G4R1 (1), IIaA19G3R1a (80), IIaA19G3R1b (1), IIaA20G2R1 (9), IIaA20G3R1 (1), IIaA20G4R1 (9), IIaA21G3R1 (1) and IIaA23G3R1 (9), of which IIaA18G2R1b, IIaA18G4R1 and IIaA19G3R1b are new records. All of the subgenotypes, except IIaA16G3R1, IIaA18G4R1 and IIaA20G4R1, have been detected previously in humans and are thus considered to be of zoonotic relevance. (Nucleotide sequences reported in this paper are available in the GenBank database under accession numbers FJ825018‐FJ825029).
Searching for serum tumor markers for colorectal cancer using a 2‐D DIGE approach
Authors: Ma Yanlei , Peng Jiayuan , Huang Long , Liu Weijie , Zhang Peng , Qin Huanlong
Published: July 2009

Identification of specific protein markers for colorectal cancer (CRC) could provide a basis for its early diagnosis and detection, as well as clues to the molecular mechanisms governing cancer progression. In the present study, 2‐D DIGE coupled with MS was used to screen for biomarker candidates in the serum proteome of ten human CRC samples and ten healthy control samples. After pooling identical amounts of serum proteins (based on total protein concentration), albumin/IgG was depleted under partially denaturing conditions. Subsequently, the serum samples were labeled with three different CyDyes, and separated by 2‐D DIGE. After analysis with the biological variation analysis module of the DeCyder software, only three spots were found to be significantly elevated in all patient groups (with ratios from 1.52 to 9.08), whereas five spots were significantly down‐regulated in patients (with ratios from −1.23 to −10.21) (t‐test; p<0.05). Finally, two potential biomarkers, Transaldolase 1 and thyroid receptor interactor, were chosen for validation and analysis by ELISA with the serum of 30 CRC patients and 30 healthy controls. The serum levels of the two proteins correlated well with the 2‐D DIGE results. Thus, 2‐D DIGE approaches show great promise for biomarker discovery in CRC.
Genetic categorization of Echinococcus granulosus from humans and herbivorous hosts in Iran using an integrated mutation scanning‐phylogenetic approach
Authors: Sharbatkhori Mitra , Mirhendi Hossein , Jex Aaron R. , Pangasa Aradhana , Campbell Bronwyn E. , Kia Eshrat B. , Eshraghian Mohammad R. , Harandi Majid F. , Gasser Robin B.
Published: July 2009

In the present study, we have extended earlier taxonomic, biochemical and experimental investigations to characterize Echinococcus granulosus from various hosts in Iran utilizing DNA regions (designated pcox1 and pnad1) within the cytochrome c oxidase subunit 1 and NADH dehydrogenase 1 mitochondrial genes, respectively. An emphasis was placed on the characterization of E. granulosus isolates (cyst material) from humans, sheep, goats, cattle and camels, and on assessing their genetic relationships. PCR‐based SSCP analysis of pcox1 and pnad1 amplicons derived from individual isolates (n=148) of E. granulosus revealed five (pc1–pc5) and nine (pn1–pn9) electrophoretic profiles, respectively. Sequencing of pcox1 and pnad1 amplicons representing unique SSCP profiles demonstrated that each profile was linked unequivocally to a particular sequence and that single point mutations were readily detectable by SSCP. Phylogenetic analyses of pcox1 and/or pnad1 nucleotide sequence data were conducted using Bayesian inference and maximum likelihood tree‐building methods. Following the phylogenetic analyses of concatenated pcox1+pnad1 sequence data, including representatives of all presently recognized Echinococcus species/genotypes as well as Taenia saginata (as the outgroup), the majority of cyst isolates (142 of 148; 95.9%) from humans, ruminants (sheep, goats and cattle) and camels were assigned to the G1–G3 complex of E. granulosus (or E. granulosus sensu stricto), whereas some E. granulosus cysts (6 of 19; 31.6%) from camels were assigned to the G6–G10 complex (or E. canadensis). The present study reinforces the advantages of the mutation scanning‐sequencing‐phylogenetic approach to explore variation in multiple mitochondrial loci within and among Echinococcus populations, which provides a platform for future, detailed studies of the molecular epidemiology of E. granulosus in Iran and other countries. (Note: The sequences determined in the present study have been deposited in the GenBank database under accession numbers: FJ796203‐FJ796207 (pcox1) and FJ796208‐FJ796216 (pnad1)).
Two‐dimensional modeling for stability analysis of two‐phase stratified flow
Authors: Heidarinejad Ghassem , Sani Abdollah Eskandari
Published: July 2009

The effect of wavelength and relative velocity on the disturbed interface of two‐phase stratified regime is modeled and discussed. To analyze the stability, a small perturbation is imposed on the interface. Growth or decline of the disturbed wave, relative velocity, and surface tension with respect to time will be discussed numerically. Newly developed scheme applied to a two‐dimensional flow field and the governing Navier–Stokes equations in laminar regime are solved. Finite volume method together with non‐staggered curvilinear grid is a very effective approach to capture interface shape with time. Because of the interface shape, for any time advancement, a new grid is performed separately on each stratified field, liquid, and gas regime. The results are compared with the analytical characteristics method and one‐dimensional modeling. This comparison shows that solving the momentum equation including viscosity term leads to physically more realistic results. In addition, the newly developed method is capable of predicting two‐phase stratified flow behavior more precisely than one‐dimensional modeling. It was perceived that the surface tension has an inevitable role in dissipation of interface instability and convergence of the two‐phase flow model. Copyright © 2009 John Wiley & Sons, Ltd.
A surface remeshing technique for a Lagrangian description of 3D two‐fluid flow problems
Authors: Cruchaga Marcela , Celentano Diego , Breitkopf Piotr , Villon Pierre , Rassineux Alain
Published: July 2009

Classical Lagrangian schemes applied to update the front position between two immiscible incompressible fluids have been long recognized to provide a sharp representation of the interface. However, the main drawback of these approaches is the progressive distortion in the distribution of the markers used to identify the material front. To avoid this problem, a 3D interface remeshing algorithm is proposed in this work. In addition, the remeshed front is enforced to preserve the global volume. These aspects are incorporated in an existing fluid dynamics formulation for the analysis of two‐fluid flows problems. The resulting formulation, called as the 3D‐moving Lagrangian interface remeshing technique, is applied in the numerical analysis of two‐fluid flow problems. Copyright © 2009 John Wiley & Sons, Ltd.
Comparing vortex methods and finite difference methods in a homogeneous turbulent shear flow
Authors: Yokota R. , Obi S.
Published: July 2009

The vortex method is applied to the calculation of a homogeneous shear turbulence, and compared with a finite difference code using identical calculation conditions. The core spreading method with spatial adaptation is selected as the viscous diffusion scheme of the vortex method. The shear rate is chosen so that it matches the maximum value observed in a fully developed channel flow. The isosurface, anisotropy tensors, and joint probability density functions reflect the ability of the present vortex method to quantitatively reproduce the anisotropic nature of strongly sheared turbulence, both instantaneously and statistically. Copyright © 2009 John Wiley & Sons, Ltd.
Local trader profitability in futures markets: Liquidity and position taking profits
Authors: Frino Alex , Jarnecic Elvis , Feletto Roger
Published: July 2009

This study examines the profitability of local traders on floor‐traded futures markets. Using unique data from the period of floor trading on the Sydney Futures Exchange, local income is decomposed into liquidity and position‐taking profit components. Locals on the trading floor are found to make significant position‐taking profits. Moreover, the ability of locals on the floor to derive position‐taking profits is positively related to order‐flow related information, and negatively related to the presence of exogenous information, local liquidity profits and the length of a locals inventory cycle. Accordingly, this paper characterizes locals as active informed traders. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 30:1–24, 2010
A copula‐based regime‐switching GARCH model for optimal futures hedging
Authors: Lee Hsiang‐Tai
Published: July 2009

The article develops a regime‐switching Gumbel–Clayton (RSGC) copula GARCH model for optimal futures hedging. There are three major contributions of RSGC. First, the dependence of spot and futures return series in RSGC is modeled using switching copula instead of assuming bivariate normality. Second, RSGC adopts an independent switching Generalized Autoregressive Conditional Heteroscedasticity (GARCH) process to avoid the path‐dependency problem. Third, based on the assumption of independent switching, a formula is derived for calculating the minimum variance hedge ratio. Empirical investigation in agricultural commodity markets reveals that RSGC provides good out‐of‐sample hedging effectiveness, illustrating importance of modeling regime shift and asymmetric dependence for futures hedging. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:946–972, 2009
Liquidity and hedging effectiveness under futures mispricing: International evidence
Authors: Andani A. , Lafuente J. A. , Novales A.
Published: July 2009

We analyze the hedging effectiveness of positions that replicate stock indexes using corresponding futures contracts through the application of a dynamic, stochastic hedging strategy proposed by Lafuente, J. A. and Novales, A. (2003). Conclusive gains do not emerge in any of the markets analyzed over the period considered, relative to the use of a constant unit hedge ratio. These findings are consistent with the trend observed in the IBEX 35 futures market study of Lafuente, J. A. and Novales, A. (2003). Our empirical evidence suggests that, contrary to what happens in less liquid markets, the discrepancy between theoretical and quoted prices in index futures contracts in fully developed markets does not represent a noise factor that can be successfully exploited for hedging. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:1050–1066, 2009
Reverse convertible bonds analyzed
Authors: Szymanowska Marta , Horst Jenke Ter , Veld Chris
Published: July 2009

We study the pricing of reverse convertible (RC) bonds. These are bonds that carry high coupon payments. In exchange, the issuer has an option at the maturity date to either redeem the bonds in cash or to deliver a pre‐specified number of shares. We find that Dutch plain vanilla and knock‐in RC bonds are, on average, overpriced by almost 6%. This overpricing is confirmed in a model‐free analysis with respect to option‐ and bond‐pricing models. We find that rational factors explain 23% of the documented overpricing. In addition, we find that the combination of financial marketing, framing, and the representativeness bias further increases our ability to explain the documented overpricing to more than 35%. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:895–919, 2009
The CBOE S&P 500 three‐month variance futures
Authors: Zhang Jin E. , Huang Yuqin
Published: July 2009

In this article, we study the market of the Chicago Board Options Exchange S&P 500 three‐month variance futures that were listed on May 18, 2004. By using a simple mean‐reverting stochastic volatility model for the S&P 500 index, we present a linear relation between the price of fixed time‐to‐maturity variance futures and the VIX2. The model prediction is supported by empirical tests. We find that a model with a fixed mean‐reverting speed of 1.2929 and a daily‐calibrated floating long‐term mean level has a good fit to the market data between May 18, 2004, and August 17, 2007. The market price of volatility risk estimated from the 30‐day realized variance and VIX2 has a mean value of −19.1184. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 30:48–70, 2010
The bias in time series volatility forecasts
Authors: Ederington Louis H. , Guan Wei
Published: July 2009

By Jensen's inequality, a model's forecasts of the variance and standard deviation of returns cannot both be unbiased. This study explores the bias in GARCH type model forecasts of the standard deviation of returns, which we argue is the more appropriate volatility measure for most financial applications. For a wide variety of markets, the GARCH, EGARCH, and GJR (or TGARCH) models tend to persistently over‐estimate the standard deviation of returns, whereas the ARLS model of L. Ederington and W. Guan (2005a) does not. Furthermore, the GARCH and GJR forecasts are especially biased following high volatility days, which cause a large jump in forecast volatility, which is rarely fully realized. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 30:305–323, 2010
Are credit spreads too low or too high? A hybrid barrier option approach for financial distress
Authors: Lin William , Sun David
Published: July 2009

Based on the works of Brockman, P. and Turtle, H. J. (2003) and Giesecke, K. (2004), we propose in this study a hybrid barrier option model to explain observed credit spreads. It is free of problems with the structural model, which underprescribed credit spreads for investment grade corporate bonds and overprescribed the high‐yield issues. Unlike the standard barrier option approach, our hybrid model does not imply, for high‐yield issues with firms under financial stress, a reduction of credit spreads while firm value actually falls. Our empirical analysis supports that when credit spreads are quoted abnormally higher or rising faster than expected, unexpected changes tend to persist. Otherwise a significant and prompt reversion to long‐term equilibrium takes place. This asymmetric pricing phenomenon is validated with a method introduced by Enders, W. and Granger, C. W. J. (1998) and Enders, W. and Siklos, P. L. (2001). The pricing asymmetry could not have been produced by a structural model employing only standard option. But it is consistent with a hybrid barrier option model. Our model characterizes the valuation of debt under financial stress and the asymmetric price pattern better than both the classical structural and the standard barrier option approaches. It can be extended to the study of individual CDS for its better liquidity than individual corporate bonds. This study provides helpful implications especially for the medium and high‐yield issues in pricing as well as portfolio diversification. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:1161–1189, 2009
The impact of volatility derivatives on S&P500 volatility
Authors: Dawson Paul , Staikouras Sotiris K.
Published: July 2009

This study investigates whether the newly cultivated platform of volatility derivatives has altered the volatility of the underlying S&P500 index. The findings suggest that the onset of the volatility derivatives trading has lowered the volatility of both the cash market volatility and the cash market index, and significantly reduced the impact of shocks to volatility. When big sudden events hit financial markets, however, the volatility of volatility seems to elevate in the U.S. equity market as a result of increased global correlations. Regardless of the period under examination and the estimator employed, long‐run volatility persistence is present. The latter drops significantly when the credit crunch period is excluded from the post‐event date sample period. The correlation between the broad equity index and the return volatility remains low, which in turn strengthens the role of volatility derivatives to facilitate portfolio diversification. The analysis also shows that volatility is mean reverting, whereas market data support the impact of information asymmetries on conditional volatility. In the post‐event date phase, no asymmetries are found when the recent crisis is not accounted for. Finally, comparisons with other international equity indices, with no volatility derivatives listed, unveil that these indices exhibit higher volatility and slower recovery from shocks than the S&P500 index. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 29:1190–1213, 2009
Effects of omitting information variables on optimal hedge ratio estimation: A note
Authors: Lien Donald
Published: July 2009

Suppose that there is an information variable (with error correction variable being a special case) affecting the spot price but not the futures price. The estimated optimal hedge ratio is unbiased but inefficient when this variable is omitted. In addition, the resulting hedging effectiveness is smaller than that provided by the efficient hedge ratio. © 2009 Wiley Periodicals, Inc. Jrl Fut Mark 30:795–800, 2010
An efficient algorithm for multistate protein design based on FASTER
Authors: Allen Benjamin D. , Mayo Stephen L.
Published: July 2009

Most of the methods that have been developed for computational protein design involve the selection of side‐chain conformations in the context of a single, fixed main‐chain structure. In contrast, multistate design (MSD) methods allow sequence selection to be driven by the energetic contributions of multiple structural or chemical states simultaneously. This methodology is expected to be useful when the design target is an ensemble of related states rather than a single structure, or when a protein sequence must assume several distinct conformations to function. MSD can also be used with explicit negative design to suggest sequences with altered structural, binding, or catalytic specificity. We report implementation details of an efficient multistate design optimization algorithm based on FASTER (MSD‐FASTER). We subjected the algorithm to a battery of computational tests and found it to be generally applicable to various multistate design problems; designs with a large number of states and many designed positions are completely feasible. A direct comparison of MSD‐FASTER and multistate design Monte Carlo indicated that MSD‐FASTER discovers low‐energy sequences much more consistently. MSD‐FASTER likely performs better because amino acid substitutions are chosen on an energetic basis rather than randomly, and because multiple substitutions are applied together. Through its greater efficiency, MSD‐FASTER should allow protein designers to test experimentally better‐scoring sequences, and thus accelerate progress in the development of improved scoring functions and models for computational protein design. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
A universal scale of aromaticity for π‐organic compounds
Authors: Alonso Mercedes , Herradón Bernardo
Published: July 2009

Aromaticity is an essential concept in chemistry, invented to account for the stability, reactivity, molecular structure, and properties of many organic and inorganic compounds. In recent years, numerous methods to quantify aromaticity based on the energetic, magnetic, structural, and electronic properties of molecules have been proposed but none of them is universal. The inability of establishing a universal scale of aromaticity based on a single parameter is due to the multidimensional character of this phenomenon. Consequently, aromaticity analyses should be carried out by employing a set of aromaticity descriptors on the basis of different physical manifestations of aromaticity. Here, we report a universal scale of aromaticity for π‐organic compounds based on the Euclidean distance between neurons in a self‐organizing map. The most widely used aromaticity indicators have been used as molecular descriptors, and so our approach provides the first scale of aromaticity which contains the energetic, magnetic, and structural aspects of this property. The method is applicable to a wide variety of unsaturated organic compounds and allows quantification of both aromaticity and antiaromaticity. Additionally, the position of a compound on the bidimensional map determinates immediately the following: (a) the group (aromatic, nonaromatic, or antiaromatic) to which the system belongs, (b) their degree of π‐electronic delocalization, and (c) the similarity in aromaticity/antiaromaticity between different compounds. This new scale of aromaticity is able to indicate the expected order of aromaticity of analogues of fulvene and heptafulvene, heteroaromatic species, substituted benzenes, and functionalized cyclopentadienyl compounds. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Expression of Concern: Aurora B expression in post‐puberal testicular germ cell tumours
Authors: Esposito Francesco , Libertini Silvana , Franco Renato , Abagnale Antonella , Marra Luigi , Portella Giuseppe , Chieffi Paolo
Published: July 2009

Aurora/Ipl1‐related kinases are a conserved family of proteins that are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumours and have been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy, and genomic instability. Previous studies of our group have shown that Aurora B expression is restricted to specific germinal cells. In this study, we have evaluated by immunohistochemical analysis Aurora B expression in post‐puberal testicular germ cell tumours (22 seminomas, 2 teratomas, 15 embryonal carcinomas, 5 mixed germinal tumours with a prominent yolk sac tumour component and 1 choriocarcinoma). The Aurora B protein expression was detected in all intratubular germ cell tumours, seminomas and embryonal carcinomas analysed but not in teratomas and yolk sac carcinomas. The immunohistochemical data were further confirmed by Western blot analysis. In addition, the kinase Aurora B was vigorously expressed in GC‐1 cells line derived from murine spermatogonia. The block of Aurora B function induced by a pharmacological inhibitor significantly reduced the growth of GC‐1 cells suggesting that Aurora B is a potential therapeutic target. J. Cell. Physiol. 221: 435–439, 2009. © 2009 Wiley‐Liss, Inc.
Single‐dose lentiviral gene transfer for lifetime airway gene expression
Authors: Stocker Alice G. , Kremer Karlea L. , Koldej Rachel , Miller Darren S. , Anson Donald S. , Parsons David W.
Published: July 2009

Background

Cystic fibrosis (CF) is caused by a defect in cystic fibrosis transmembrane conductance regulator (CFTR) activity, often resulting in an incurable airway disease. Gene therapy into the conducting airway epithelium is a potential cure for CF; however, most gene vectors do not result in long‐lived expression, and require re‐dosing. Perversely, intrinsic host immune responses can then block renewed gene transfer.

Methods

To investigate whether persistent gene expression could be achieved after a single dosing event, thus avoiding the issue of blocking host responses, we used a gene transfer protocol that combined an airway pretreatment using lysophosphatidylcholine with a human immunodeficiency virus type‐1 (vesicular stomatitis virus G pseudotype) derived lentiviral vector to test whether an integrating vector could produce gene expression able to last for a substantial part of the lifetime of the laboratory mouse.

Results

We found that a single dose of LV‐LacZ produced immediate as well as lifetime mouse airway expression, confirming our hypothesis that use of an integrating vector extends transgene expression. Importantly, LV‐CFTR dosing achieved at least 12 months of CFTR expression, representing partial functional correction of the CFTR defect in CF‐null mice.

Conclusions

These findings validate the potential of this methodology for developing a gene transfer treatment for CF airway disease. Copyright © 2009 John Wiley & Sons, Ltd.
Exhalation of respiratory viruses by breathing, coughing, and talking
Authors: Stelzer‐Braid Sacha , Oliver Brian G. , Blazey Angus J. , Argent Elizabeth , Newsome Timothy P. , Rawlinson William D. , Tovey Euan R.
Published: July 2009

There is a lack of quantitative information about the generation of virus aerosols by infected subjects. The exhaled aerosols generated by coughing, talking, and breathing were sampled in 50 subjects using a novel mask, and analyzed using PCR for nine respiratory viruses. The exhaled samples from a subset of 10 subjects who were PCR positive for rhinovirus were also examined by cell culture for this virus. Of the 50 subjects, among the 33 with symptoms of upper respiratory tract infections, 21 had at least one virus detected by PCR, while amongst the 17 asymptomatic subjects, 4 had a virus detected by PCR. Overall, rhinovirus was detected in 19 subjects, influenza in 4 subjects, parainfluenza in 2 subjects, and human metapneumovirus in 1 subject. Two subjects were co‐infected. Of the 25 subjects who had virus‐positive nasal mucus, the same virus type was detected in 12 breathing samples, 8 talking samples, and in 2 coughing samples. In the subset of exhaled samples from 10 subjects examined by culture, infective rhinovirus was detected in 2. These data provide further evidence that breathing may be a source of respirable particles carrying infectious virus. J. Med. Virol. 81:1674–1679, 2009. © 2009 Wiley‐Liss, Inc.
Dynamic changes of HBV quasispecies and deletion patterns in a chronic hepatitis B patient
Authors: Ji Fen , Zhou Li , Ma Sufang , Li Feifei , Ding Huiguo , Zeng Changqing
Published: July 2009

Hepatitis B virus (HBV) infection is a dynamic process during which molecular variants are selected continuously to adapt to changes. In addition to drug resistant mutations, sequential antiviral therapy may also lead to the selection of deleted mutants. To investigate this process, the following samples were collected from a patient who failed lamivudine therapy and then was switched to adefovir dipivoxil. HBV DNA was sequenced at two separate regions; a 1 kb region of reverse transcriptase (RT) and a 1.5 kb region encompassing the C gene and part of the preS gene. Sequence analysis of the RT region showed that the prevailing lamivudine resistant mutations were reduced after switching to adefovir dipivoxil, and ultimately the mutations were undetectable. Quasispecies distribution and deletion patterns in the C and preS regions were also different between the two antiviral therapies. In lamivudine‐treated samples, wild‐type strains (57.7%) were dominant and deletions in the preS region were observed. However, in the subsequent therapy involving adefovir dipivoxil, a virus population harboring 81 and 96 bp deletions (86%) in the C gene prevailed. Both major deletions encompassed T‐ and B‐cell epitopes. Meanwhile, the frequencies of the preS deletions decreased significantly, except for the 129 bp deletion. Notably, the presence of 81, 96, and 129 bp deletions was always accompanied with some nucleotide substitutions. In conclusion, the prevalence of deletions at the C gene epitopes accompanied with the gradual disappearance of lamivudine resistance mutations may contribute to the survival of HBV under sequential antiviral therapy. J. Med. Virol. 81:1551–1559, 2009. © 2009 Wiley‐Liss, Inc.