bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendrite‐Assisted Growth of Silicon Nanowires in Electroless Metal Deposition
Authors: Peng K. , Yan Y. , Gao S. , Zhu J.
Published: February 2003

This article concerns the detailed investigations on the silver dendrite‐assisted growth of single‐crystalline silicon nanowires, and their possible self‐assembling nanoelectrochemistry growth mechanism. The growth of silicon nanowires was carried out through an electroless metal deposition process in a conventional autoclave containing aqueous HF and AgNO3 solution near room temperature. In order to explore the mechanism and prove the centrality of silver dendrites in the growth of silicon nanowires, other etching solution systems with different metal species were also investigated in this work. The morphology of etched silicon substrates strongly depends upon the composition of the etching solution, especially the metal species. Our experimental results prove that the simultaneous formation of silver dendrites is a guarantee of the preservation of free‐standing nanoscale electrolytic cells on the silicon substrate, and also assists in the final formation of silicon nanowire arrays on the substrate surface.
Structural Effects in the Electrodeposition of CdSe Quantum Dots on Mechanically Strained Gold
Authors: Ruach‐Nir I. , Wagner H.D. , Rubinstein I. , Hodes G.
Published: February 2003

CdSe nanoparticles were electrodeposited on mechanically strained gold, the latter achieved by controlled bending of gold films evaporated on mica. It is shown that the size and bandgap of the electrodeposited CdSe quantum dots (QDs) can be varied by applying mechanical strain to the Au substrate during deposition. This is attributed to change in the lattice spacing of the strained {111} Au and consequently in the lattice mismatch between the Au and the CdSe. Negative mechanical strain promotes the formation of rocksalt (RS) CdSe nanocrystals, normally existing only at high pressures. This is attributed to surface tension compression in the small crystals, together with enhancement of the phase transition by the CdSe/substrate interface.
Porous Polymer and Cell Composites That Self‐Assemble In Situ
Authors: Salem A.K. , Rose F.R.A.J. , Oreffo R.O.C. , Yang X. , Davies M.C. , Mitchell J.R. , Roberts C.J. , Stolnik‐Trenkic S. , Tendler S.J.B. , Williams P.M. , Shakesheff K.M.
Published: February 2003

A cell‐laden 3D network is formed upon the addition of avidin to biotinylated polymer particles in the presence of a suspension of cells (see Figure). Applications in tissue engineering and drug delivery are demonstrated; a shape‐retaining biomaterial is formed within minutes of injecting the components into a cavity. The molecular interaction mechanism of self‐assembly differentiates this polymer/cell composite from other injectable systems.
Dynamic Addressing of a Surface Pattern by a Stimuli‐Responsive Fusion Protein
Authors: Frey W. , Meyer D.E. , Chilkoti A.
Published: February 2003

Thermodynamically reversible addressing of proteins (TRAP) is demonstrated. A stimuli‐responsive elastin‐like polypeptide fused to thioredoxin is used to reversibly address the fusion protein onto a chemically micropatterned surface template by switching the interaction between the surface and the stimuli‐ responsive polypeptide (see Figure).
Covalent and Non‐covalent Attachment and Patterning of Polypyrrole at Silicon Surfaces
Authors: Pike A.R. , Patole S.N. , Murray N.C. , Ilyas T. , Connolly B.A. , Horrocks B.R. , Houlton A.
Published: February 2003

DNA and alkenyl pyrrole functionalized silicon surfaces allow for the formation of silicon/polypyrrole junctions. These junctions are spatially controlled by photolithography (see Figure) and selective photo‐assisted electro‐oxidation of pyrrole. This process shows promise for use in the development of molecular‐based electronic devices, and could enable the deposition of polypyrrole analogously to metal ions in the formation of metallic wires.
Effect of ecdysone agonists on vitellogenesis and the expression of EcR and USP in codling moth (Cydia pomonella)
Authors: Sun Xiaoping , Song Qisheng , Barrett Bruce
Published: February 2003

The effects of tebufenozide and methoxyfenozide on vitellogenin (Vg) synthesis/release in the fat body, translocation in hemolymph, uptake by the ovary, and the expression of the ecdysone receptor (EcR) and its heterodimer partner, ultraspiracle protein (USP) in fat body, were investigated in Cydia pomonella. The results indicated that both ecdysone agonists significantly increased the Vg level in the adult hemolymph when the moths were exposed to agonist‐treated surfaces. However, these agonists did not affect Vg release from the fat body nor Vg deposition in the first batch oocytes. Western blot analysis revealed that the expression of EcR and USP was significantly increased in tebufenozide‐ and methoxyfenozide‐treated samples compared to the control, suggesting that ecdysone agonists regulated the Vg synthesis via the EcR and USP proteins complex. Arch. Insect Biochem. Physiol. 52:115–129, 2003. © 2003 Wiley‐Liss, Inc.
Small GTP binding proteins: Rab GTPases from the brain of Bombyx mori
Authors: Uno Tomohide , Hiragaki Susumu
Published: February 2003

From a mRNA of the brain of Bombyx mori, we isolated 8 cDNA clones (BRabs), each of which encodes a different member of Rab‐protein family. Four of them have more than 80% amino acid identity to the corresponding members of Drosophila Rab proteins. The other 4 proteins show low sequence similarity to any of the known Rab proteins. However, all of them contain the region conserved in rab protein. Using RACE (Rapid Amplification of cDNA ends), the one full‐length cDNA clone (BRab14) was isolated. The clone was expressed in Escherichia coli as a glutathione S‐transferase (GST) fusion protein. After purification, the fusion protein was cut with protease to remove GST‐Tag and applied to a glutathione S‐Sepharose column. The protein bound [3H]‐GDP with association constant of 1.02 × 1011 M–1. Further, the protein was phosphorylated by protein kinase. This result suggests that Rab protein in the brain of Bombyx mori binds GDP or GTP and its function is regulated by phosphorylation. Arch. Insect Biochem. Physiol. 52:130–138, 2003. © 2003 Wiley‐Liss, Inc.
Organ‐specific distribution of the calcium sensor CaMKII in Locusta migratoria
Authors: Braak Sandra , Fährmann Michael
Published: February 2003

The Ca2+/calmodulin‐dependent kinase CaMKII is a key signaling component in Ca2+‐dependent physiological processes. The expression and function of CaMKII in insect brain is well documented but less investigated for other tissues of insects. The present study demonstrates that in the locust Locusta migratoria CaMKII is widely expressed in various tissues. Relatively high expression levels of CaMKII were found in the brain, upper part of the digestive tract (pharynx, esophagus), and the flight and leg muscles. The different expression patterns of CaMKII in various tissues, as well as different molecular masses of CaMKII between 48 and 60 kDa indicate a tissue‐specific expression of CaMKII variants. The expression was monitored with a polyclonal anti‐(rat)CaMKII antibody. About 60% of total CaMKII activity in flight muscle cells is associated to the myofibril‐rich, particulate fraction suggesting an important role of CaMKII in sarcomeric function. Arch. Insect Biochem. Physiol. 52:155–162, 2003. © 2003 Wiley‐Liss, Inc.
Resolving the source populations that contribute to the X‐ray background: The 2 Ms Chandra Deep Field‐North Survey
Authors: Alexander D. M. , Bauer F. E. , Brandt W. N. , Garmire G. P. , Hornschemeier A. E. , Schneider D. P. , Vignali C.
Published: February 2003

With ≈ 2 Ms of exposure, the Chandra Deep Field‐North (CDF‐N) survey provides the deepest view of the Universe in the 0.5–8.0 keV band. Five hundred and three (503) X‐ray sources are detected down to on‐axis 0.5–2.0 keV and 2–8 keV flux limits of ≈ 1.5 × 10–17 erg cm–2 s–1 and ≈ 1.0 × 10–16 erg cm–2 s–1, respectively. These flux limits correspond to L0.5–8.0 keV≈ 3 × 1041 erg s–1 at z = 1 and L0.5–8.0 keV≈ 2 × 1043 erg s–1 at z = 6; thus this survey is sensitive enough to detect starburst galaxies out to moderate redshift and Seyfert galaxies out to high redshift.We present the X‐ray observations, describe the broad diversity of X‐ray selected sources, and review the prospects for deeper exposures.
Chandra Deep Field South: the optically faint population
Authors: Mainieri V. , Rosati P. , Nonino M. , Szokoly G. , Bergeron J. , Hasinger G. , Lehmann I. , Tozzi P. , CDFS Team
Published: February 2003

A not negligible fraction (∼15%) of X‐ray sources detected in the 1 Msec observation of the Chandra Deep Field South (CDFS) are not detected down to R ≃ 27, however they are registered in deep near‐IR imaging.We use deep multicolor photometry from the VLT (FORS+ISAAC instruments), covering a broad wavelength range, to discuss the adequacy of such techniques for X‐ray selected sources and to constrain the nature of this optically faint population.
XMM‐Newton view of the Hubble Deep Field‐North and Groth‐Westphal strip regions
Authors: Miyaji T. , Griffiths R.E. , Lumb D. , Sarajedini V. , Siddiqui H.
Published: February 2003

We report the progress on our analysis of two deep XMM observations in the areas of Hubble Deep Field‐North and the Groth‐Westphal Strip field. We present the source detection method, Monte‐Carlo simulation on source detection, and our preliminary Log N – Log S relations. Comparing these two fields and other fields in literature, we find up to ∼30% variations in number counts near our flux limits, which are most likely to be due to cosmic variance. This serves as a pilot study for a more systematic investigation. The nature of the X‐ray sources in the Groth‐Westphal field is also discussed in terms of hardness ratios, morphology and spectroscopic properties.
Unconventional AGN in hard X‐ray surveys
Authors: Comastri A. , Brusa M. , Mignoli M. , The Hellas2xmm Team
Published: February 2003

Extensive programs of follow–up observations of hard X–ray selected sources have unambiguously revealed that the sources of the X–ray background are characterized by an extremely large dispersion in their optical magnitude and spectroscopic classification. Here we present the results of an attempt to understand the nature of the observed variety using a simple prescription for their optical to X–ray energy distribution.
The hard X‐ray luminosity function from ASCA surveys
Authors: Ueda Y. , Akiyama M. , Ohta K. , Miyaji T.
Published: February 2003

We summarize the nature of hard X‐ray populations at “bright” fluxes > 10–13 erg cm–2 s–1 (2–10 keV) from optical identification of ASCA surveys, and present results of the hard X‐ray luminosity function (HXLF) of Active Galactic Nuclei (AGN). Combined with HEAO1 and Chandra surveys we construct a hard‐band selected sample with extremely high degree of completeness (>95%), consisting of 228 AGNs over the flux range 10–11 ≈ 3 × 10–15 erg cm–2 s–1 (2–10 keV). We find evidence that the percentage of “type‐II” AGNs decreases with the intrinsic luminosity. The intrinsic HXLF of the whole AGNs (including type‐II AGNs) is well described with the pure luminosity evolution (PLE) model up to redshift of 3. Our results directly constrain the evolution of AGNs that produce a major part of the hard X‐ray background.
Chandra multi‐wavelength plane (ChaMPlane) survey: design and initial results
Authors: Grindlay J. , Zhao P. , Hong J.S. , Jenkins J. , Kim Dong‐Woo , Schlegel E. , Drake J. , Kashyap V. , Edmonds P. , Cohn H. , Lugger P. , Cool A.
Published: February 2003

The Chandra Multiwavength Plane (ChaMPlane) Survey of the galactic plane incorporates serendipitous sources from selected Chandra pointings in or near the galactic plane (b < 12°; ≥20 ksec; lack of bright diffuse or point sources) to measure or constrain the luminosity function of low‐luminosity accretion sources in the Galaxy. The primary goal is to detect and identify accreting white dwarfs (cataclysmic variables, with space density still uncertain by a factor of >10‐100), neutron stars and black holes (quiescent low mass X‐ray binaries) to constrain their space densities and thus origin and evolution. Secondary objectives are to identify Be stars in high mass X‐ray binaries and constrain their space densities, and to survey the H‐R diagram for stellar coronal sources. A parallel optical imaging under the NOAO Long Term Survey program provides deep optical images using the Mosaic imager on the CTIO and KPNO 4‐m telescopes. The 36′ × 36′ optical images (Hα, R, V and I) cover ∼ 5× the area of each enclosed Chandra ACIS FOV, providing an extended survey of emission line objects for comparison with Chandra. Spectroscopic followup of optical counterparts is then conducted, thus far with WIYN and Magellan. The X‐ray preliminary results from both the Chandra and optical surveys will be presented, including logN‐logS vs. galactic position (l,b) and optical identifications.
The source content of low galactic latitude XMM‐Newton surveys
Authors: Motch C. , Herent O. , Guillout P.
Published: February 2003

We present results from a project conducted by the Survey Science Center of the XMM‐Newton satellite and aiming at the identification and characterisation of serendipitous EPIC sources at low galactic latitudes. Deep multi‐colour optical imaging and spectroscopic observations have been obtained in the framework of several observing campaigns carried out at ING, CFHT and ESO. These observations have lead to a number of optical identifications, mostly with active stars. We describe the identified source content at low galactic latitudes and compare stellar populations properties at low and high galactic latitudes with those expected from stellar X‐ray count models.
The Chandra Multi‐wavelength Project (ChaMP): Results and prospects
Authors: Green Paul J. , Cameron Rob , Ghosh Himel , Grimes John , Kim Dong‐Woo , Morris David , Mossman Amy , Silverman John , Wilkes Belinda , Baldwin Jack , Jannuzi Buell , Harnden Rick , Kashyap Vinay , LaCluyzé Aaron , Maksym Peter , Schlegel Eric , Tananbaum Harvey , Vikhlinin Alexey , Smith Chris , Smith Malcolm , The Champ Collaboration
Published: February 2003

The cosmic diffuse X‐ray background radiation has been almost completely resolved into point sources by Chandra and XMM. However, the nature and evolution of those sources are just beginning to be investigated. The answers are key to our understanding of the inter‐relationship over cosmic time of (a) the formation and growth of black holes, (b) star formation, and (c) hierarchical structure formation. This requires multiwavelength followup of Chandra sources over a large area. The Chandra Multiwavelength Project (ChaMP) is a serendipitous survey of the X‐ray sky, covering about 14 deg2 of sky in the X‐ray flux range of ‐13 to ‐16 (log 0.5‐2 keV flux, cgs) and will include about 8000 sources, 70% of which are expected to be active galactic nuclei (AGN). Using Chandra archival data, we span flux limits between those reached by previous satellites and those of the deepest small‐area Chandra and XMM surveys, allowing study of larger samples of rare objects like luminous absorbed AGN, groups and clusters of galaxies, and their spatial correlations. Optical imaging and spectroscopy of the ChaMP fields are underway at a variety of telescopes using Sloan g′, r′, and i′ filters to a flux limit matched to the X‐ray such that about 75% of the X‐ray sources will be optically identified.We also plan for radio and near‐IR observations of subsets of the ChaMP sample to expand our multi‐wavelength coverage and increase the fraction of sources identified.
Optical spectroscopic followup of serendipitous Chandra sources: the Chandra Multiwavelength Project (ChaMP)
Authors: Silverman J. , Green P. , Wilkes B. , Foltz C. , Smith P. , Smith C. , Kim Dong‐Woo , Morris D. , Mossman A. , Cameron R. , Adelberger K. , The Champ Collaboration
Published: February 2003

A primary goal of the Chandra Multiwavelength Project (ChaMP) is to investigate the evolution of Active Galactic Nuclei (AGN) and quasars by measuring the luminosity function out to z ≥ 4 including obscured AGN that have been missed by previous surveys. To do so, we are acquiring spectra of optical counterparts to serendipitious X‐ray sources detected by Chandra for classification and redshift determination. We have amassed about 200 spectra using the FLWO 1.5m, WIYN 3.5m, CTIO/4m, Magellan and the MMT 6.5m. We have classified the majority of optical counterparts as 65% broad line AGN, 14% narrow emission line galaxies and 12% absorption line galaxies. The remaining counterparts are either stars (8%) or galaxy clusters (1%). We have acquired a sample of 120 AGN in 12 Chandra fields.With a limiting magnitude of r′ = 22 for spectroscopic followup, we are able to detect quasars out to z ∼ 5 and galaxies out to z ∼ 0.7. This preliminary sample forms the foundation for our measurement of the X‐ray luminosity function of AGNs out to z ∼ 4.
High cell density cultivation of probiotics and lactic acid production
Authors: Schiraldi Chiara , Adduci Vincenzo , Valli Vivien , Maresca Carmelina , Giuliano Mariateresa , Lamberti Monica , Cartenì Maria , De Rosa Mario
Published: February 2003

The commercial interest in functional foods that contain live microorganisms, also named probiotics, is paralleled by the increasing scientific attention to their functionality in the digestive tract. This is especially true of yogurts that contain strains of lactic‐acid bacteria of intestinal origin, among these, Lactobacillus delbrueckii ssp. bulgaricus is extensively used in the dairy industry and it has been demonstrated to be a probiotic strain. In this work we describe high cell density cultivations of this microorganism also focusing on the stereospecific production of lactic acid. Key parameters such as medium composition (bactocasitone concentration) and diverse aeration conditions were explored. The results showed that the final concentration of biomass in anaerobic fermentation was lower than the one obtained in microaerophilic conditions, while it gave a very high productivity of lactic acid which was present as a racemic mixture in the permeate. Fermentation experiments carried out with air sparging, even at very low flow‐rate, led to the production of the sole L(+) lactic acid giving sevenfold increase in biomass yield in respect to the batch cultivation. Finally, a mathematical model was developed to describe the microfiltration bioprocess applied in this research considering an inhibition kinetic and enucleating a suitable mathematical description for the decrease of the transmembrane flux. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 213–222, 2003.
A light distribution model for an internally radiating photobioreactor
Authors: Suh In Soo , Lee Sun Bok
Published: February 2003

Analysis of light energy distribution in culture is important for maximizing the growth efficiency of photosynthetic cells and the productivity of a photobioreactor. To characterize the irradiance conditions in a photobioreactor, we developed a light distribution model for a single‐radiator system and then extended the model to multiple radiators using the concept of parallel translation. Mathematical expressions for the local light intensity and the average light intensity were derived for a cylindrical photobioreactor with multiple internal radiators. The proposed model was used to predict the irradiance levels inside an internally radiating photobioreactor using Synechococcus sp. PCC 6301 as a model photosynthetic microorganism. The effects of cell density and radiator number were interpreted through photographic and model simulation studies. The predicted light intensity values were found to be very close to those obtained experimentally, which suggests that the proposed model is capable of accurately interpreting the local light energy profiles inside the photobioreactor system. Due to the simplicity and flexibility of the proposed model, it was also possible to predict the light conditions in other complex photobioreactors, including optical‐fiber and pond‐type photobioreactors. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 180–189, 2003.
The annotation of RNA motifs
Authors: Leontis Neocles B. , Westhof Eric
Published: February 2003

The recent deluge of new RNA structures, including complete atomic‐resolution views of both subunits of the ribosome, has on the one hand literally overwhelmed our individual abilities to comprehend the diversity of RNA structure, and on the other hand presented us with new opportunities for comprehensive use of RNA sequences for comparative genetic, evolutionary and phylogenetic studies. Two concepts are key to understanding RNA structure: hierarchical organization of global structure and isostericity of local interactions. Global structure changes extremely slowly, as it relies on conserved long‐range tertiary interactions. Tertiary RNA–RNA and quaternary RNA–protein interactions are mediated by RNA motifs, defined as recurrent and ordered arrays of non‐Watson–Crick base‐pairs. A single RNA motif comprises a family of sequences, all of which can fold into the same three‐dimensional structure and can mediate the same interaction(s). The chemistry and geometry of base pairing constrain the evolution of motifs in such a way that random mutations that occur within motifs are accepted or rejected insofar as they can mediate a similar ordered array of interactions. The steps involved in the analysis and annotation of RNA motifs in 3D structures are: (a) decomposition of each motif into non‐Watson–Crick base‐pairs; (b) geometric classification of each basepair; (c) identification of isosteric substitutions for each basepair by comparison to isostericity matrices; (d) alignment of homologous sequences using the isostericity matrices to identify corresponding positions in the crystal structure; (e) acceptance or rejection of the null hypothesis that the motif is conserved. Copyright © 2002 John Wiley & Sons, Ltd.
Endogenous retroviruses and human evolution
Authors: Khodosevich Konstantin , Lebedev Yuri , Sverdlov Eugene
Published: February 2003

Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus, the differences between these species are unlikely to be in gene content but could be caused by inherited changes in regulatory systems. Endogenous retroviruses (ERVs) comprise ∼ 5% of the human genome. The LTRs of ERVs contain many regulatory sequences, such as promoters, enhancers, polyadenylation signals and factor‐binding sites. Thus, they can influence the expression of nearby human genes. All known human‐specific LTRs belong to the HERV‐K (human ERV) family, the most active family in the human genome. It is likely that some of these ERVs could have integrated into regulatory regions of the human genome, and therefore could have had an impact on the expression of adjacent genes, which have consequently contributed to human evolution. This review discusses possible functional consequences of ERV integration in active coding regions. Copyright © 2002 John Wiley & Sons, Ltd.
Learning about gene regulatory networks from gene deletion experiments
Authors: Schlitt Thomas , Brazma Alvis
Published: February 2003

Gene regulatory networks are a major focus of interest in molecular biology. A crucial question is how complex regulatory systems are encoded and controlled by the genome. Three recent publications have raised the question of what can be learned about gene regulatory networks from microarray experiments on gene deletion mutants. Using this indirect approach, topological features such as connectivity and modularity have been studied. Copyright © 2002 John Wiley & Sons, Ltd.
The evolution of light stress proteins in photosynthetic organisms
Authors: Heddad Mounia , Adamska Iwona
Published: February 2003

The Elip (early light‐inducible protein) family in pro‐ and eukaryotic photosynthetic organisms consists of more than 100 different stress proteins. These proteins accumulate in photosynthetic membranes in response to light stress and have photoprotective functions. At the amino acid level, members of the Elip family are closely related to light‐harvesting chlorophyll a/b‐binding (Cab) antenna proteins of photosystem I and II, present in higher plants and some algae. Based on their predicted secondary structure, members of the Elip family are divided into three groups: (a) one‐helix Hlips (high light‐induced proteins), also called Scps (small Cab‐like proteins) or Ohps (one‐helix proteins); (b) two‐helix Seps (stress‐enhanced proteins); and (c) three‐helix Elips and related proteins. Despite having different physiological functions it is believed that eukaryotic three‐helix Cab proteins evolved from the prokaryotic Hlips through a series of duplications and fusions. In this review we analyse the occurrence of Elip family members in various photosynthetic prokaryotic and eukaryotic organisms and discuss their evolutionary relationship with Cab proteins. Copyright © 2002 John Wiley & Sons, Ltd.
Meeting Highlights: International Summer School, ‘From Genome to Life’
Authors: Wixon Jo
Published: February 2003

This report from the International Summer School ‘From Genome to Life’, held at the Institute d'Etudes Scientifiques de Cargèse in Corsica in July 2002, covers the talks of the invited speakers. The topics of the talks can be broadly grouped into the areas of genome annotation, comparative and evolutionary genomics, functional genomics, proteomics, structural genomics, pharmacogenomics, and organelle genomes, epigenetics and RNA. Copyright © 2002 John Wiley & Sons, Ltd.
Flowering buds of globular proteins: transpiring simplicity of protein organization
Authors: Berezovsky Igor N. , Trifonov Edward N.
Published: February 2003

Structural and functional complexity of proteins is dramatically reduced to a simple linear picture when the laws of polymer physics are considered. A basic unit of the protein structure is a nearly standard closed loop of 25–35 amino acid residues, and every globular protein is built of consecutively connected closed loops. The physical necessity of the closed loops had been apparently imposed on the early stages of protein evolution. Indeed, the most frequent prototype sequence motifs in prokaryotic proteins have the same sequence size, and their high match representatives are found as closed loops in crystallized proteins. Thus, the linear organization of the closed loop elements is a quintessence of protein evolution, structure and folding. Copyright © 2002 John Wiley & Sons, Ltd.
The synthetic retinoid RO 13‐6307 induces neuroblastoma differentiation in vitro and inhibits neuroblastoma tumour growth in vivo
Authors: Ponthan Frida , Johnsen John Inge , Klevenvall Lena , Castro Juan , Kogner Per
Published: February 2003

Retinoids modulate cell proliferation, differentiation and apoptosis in a variety of tumour cells including leukaemia and neuroblastoma, a childhood tumour of the sympathetic nervous system. 13‐cis retinoic acid is in clinical use against minimal residual disease in neuroblastoma, where the effect seems to depend on dose, scheduling and tumour mass. Novel retinoids are searched for, to improve potency and lower toxicity. We investigated the effect of the synthetic retinoid Ro 13‐6307 on neuroblastoma growth in vitro on SK‐N‐BE(2) and SH‐SY5Y cells. Furthermore, effects on tumour growth and the toxicity profile were investigated in a rat xenograft model. Effects of Ro 13‐6307 were compared to 13‐cis RA (retinoic acid) in vitro and in vivo. Neuroblastoma cells treated with 1 μM Ro 13‐6307 exhibited neuronal differentiation, decreased proliferation and accumulation of cells in G1 phase in at least the same magnitude as 5 μM 13‐cis RA. No apoptosis was detected in vitro. Treatment of nude rats with neuroblastoma using Ro 13‐6307, 0.12 mg p.o. daily, decreased neuroblastoma growth in vivo, in terms of tumour volume during treatment and tumour weight at sacrifice (p < 0.05). In contrast, Ro 13‐6307, 0.08 mg p.o. daily, resulted in no significant reduction in tumour growth. All rats treated with Ro 13‐6307 gained less weight than control rats, but they exhibited no other signs of toxicity. The toxicity profile of Ro 13‐6307 was similar to what we found with 13‐cis RA. Our preclinical results suggest that Ro 13‐6307 may be a candidate retinoid for clinical oral therapy of neuroblastoma in children. © 2003 Wiley‐Liss, Inc.
Role of IRF‐1 and caspase‐7 in IFN‐γ enhancement of Fas‐mediated apoptosis in ACHN renal cell carcinoma cells
Authors: Tomita Yoshihiko , Bilim Vladimir , Hara Noboru , Kasahara Takashi , Takahashi Kota
Published: February 2003

Caspases exist as zymogens, and are activated by various extracellular stimuli, leading to apoptosis. One such stimulus is Fas/CD95, a member of the tumor necrosis factor receptor family, providing one means of cytotoxic T lymphocyte (CTL)‐mediated cell lysis. Clinical evidence has shown that administration of cytokine leads to regression in selected patients with renal cell carcinomas (RCCs). Interferon‐γ (IFN‐γ) indicates its contribution to anti‐tumor activity of immune cells. IFN‐γ elicits its effect through the transcription factor signal transducer and activator of transcription‐1 (STAT‐1), and through interferon regulatory factor‐1 (IRF‐1), one of the target genes of STAT‐1. Our previous study demonstrated an increase in the susceptibility of ACHN cells, established from RCC, to Fas‐mediated apoptosis by IFN‐γ, and the inhibition of this effect by the caspase‐3 and ‐7 inhibitor, DEVD‐CHO. We demonstrated the following phenomena in IFN‐γ‐treated ACHN cells: 1) enhanced transcription of caspase‐1, 3 and 7 mRNAs without any change in cleavage of their substrates; 2) increased cleavage DEVD (specific for caspase‐3 and 7), but not YVAD (for caspase‐1) or DMQD (for caspase‐3), after anti‐Fas/CD95 MAb treatment; 3) activation of the STAT‐1 and IRF‐1 pathway; and 4) partial abrogation of the IFN‐γ‐induced increase in Fas‐mediated apoptosis by antisense IRF‐1 oligodeoxynucleotide. These results suggest that IRF‐1 plays a pivotal role in the IFN‐γ‐mediated‐enhancement of Fas/CD95‐mediated apoptosis, through regulation of DEVD‐CHO‐sensitive caspases, most likely caspase‐7. © 2003 Wiley‐Liss, Inc.
Treatment of colon and breast carcinoma cells with 5‐fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA‐A(*)02.01 restricted, CEA‐peptide‐specific cytotoxic T cells in vitro
Authors: Correale Pierpaolo , Aquino Angelo , Giuliani Antonio , Pellegrini Monia , Micheli Lucia , Cusi Maria Grazia , Nencini Cristina , Petrioli Roberto , Prete Salvatore , De Vecchis Liana , Turriziani Mario , Giorgi Giorgio , Bonmassar Enzo , Francini Guido
Published: February 2003

Cancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5‐fluorouracil (5‐FU) can upregulate the expression of membrane‐associated carcino‐embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines. We have investigated whether this drug can also enhance their sensitivity to the lytic effects of CEA‐peptide specific Cytotoxic T cell lymphocytes (CTL). The CEA peptide‐specific CTLs generated in our laboratory from normal HLA‐A(*)02.01+ donor PBMCs, were able to kill HLA‐A(*)02.01+/CEA+ breast (MCF‐7‐T103) and colon (HLA‐A(*)02.01 gene‐transfected HT‐29 and C22.20) carcinoma cells in HLA‐A(*)02.01 restricted manner. The treatment of target cells with 5‐FU, enhanced their CEA expression and susceptibility to CTL‐mediated lysis. Cold competition assays confirmed these results, thus supporting the hypothesis that immune target cell lysis and 5‐FU mediated enhancement were dependent on CEA peptide presentation by cancer cells. 5‐FU treatment of functionally “mature” CTL after in vitro expansion, did not reduce their cytolytic activity against MT‐2 target cells but, when the anti‐metabolite was added during the immune‐sensitization phase, CTL generation was significantly inhibited. These results provide a rationale for investigating a possible new role of 5‐FU as an immuno targeting amplifier agent in breast and colorectal cancer patients immunized with CEA‐directed cancer vaccines. © 2003 Wiley‐Liss, Inc.
C‐Raf controlled pathways in the protection of tumor cells from apoptosis
Authors: Slater Emily P. , Stübig Thomas , Lau Quek Choon , Achenbach Tatjana V. , Rapp Ulf R. , Müller Rolf
Published: February 2003

The Raf serine‐threonine kinase is upregulated in many human tumors and plays a pivotal role in tumor cell proliferation and survival. Abrogation of c‐Raf expression by specific antisense oligonucleotides (Raf‐AS‐ODN) efficiently blocks tumor cell growth and induces apoptosis in human cancer cells. The signaling pathways and molecular mechanisms c‐Raf utilizes to mediate the survival of tumor cells are, however, not well understood. Here we show that apoptosis triggered by Raf depletion cannot be overcome by ectopic Bcl‐2 expression and occurs in the absence of cytochrome c release, arguing against a direct impact of c‐Raf on mitochondrial pathways of apoptosis regulation. We also show that c‐Raf depletion leads to a clearly decreased expression of different epidermal growth factor (EGF) receptor ligands, suggesting that the autocrine stimulation of an EGF receptor‐mediated survival pathway might be involved in the blockade of tumor cell apoptotis by c‐Raf. © 2003 Wiley‐Liss, Inc.
Lack of serological evidence for an association between simian virus 40 and lymphoma
Authors: de Sanjose Silvia , Shah Keerti V. , Domingo‐Domenech Eva , Engels Eric A. , Fernandez de Sevilla Alberto , Alvaro Tomas , Garcia‐Villanueva Mercedes , Romagosa Vicens , Gonzalez‐Barca Eva , Viscidi Raphael P.
Published: February 2003

Recent studies have implicated simian virus 40 (SV40) in non‐Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus‐like‐particle (VLP)‐based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain. © 2003 Wiley‐Liss, Inc.
Equitable resolvable coverings
Authors: van Dam Edwin R. , Haemers Willem H. , Peek Maurice B. M.
Published: February 2003

In an earlier article, Willem H. Haemers has determined the minimum number of parallel classes in a resolvable 2‐(qk,k,1) covering for all k ≥ 2 and q = 2 or 3. Here, we complete the case q = 4, by construction of the desired coverings using the method of simulated annealing. Secondly, we look at equitable resolvable 2‐(qk,k,1) coverings. These are resolvable coverings which have the additional property that every pair of points is covered at most twice. We show that these coverings satisfy k < 2q −  $\sqrt{2q - {9\over4}}$, and we give several examples. In one of these examples, k > q. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 113–123, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10024
On DRC‐covering of Kn by cycles
Authors: Bermond Jean‐Claude , Coudert David , Yu Min‐Li
Published: February 2003

This paper considers the cycle covering of complete graphs motivated by the design of survivable WDM networks, where the requests are routed on INF‐networks which are protected independently from each other. The problem can be stated as follows: for a given graph G, find a cycle covering of the edge set of Kn, where V(Kn) = V(G), such that each cycle in the covering satisfies the disjoint routing constraint (DRC7rpar;, relatively to G, which can be stated as follows: to each edge of Kn we associate in G a path and all the paths associated to the edges of a cycle of the covering must be vertex disjoint. Here we consider the case where G = Cn, a ring of size n and we want to minimize the number of cycles in the covering. We give optimal solutions for the problem as well as for variations of the problem, namely, its directed version and the case when the cycle length is fixed to 4. © 2003 Wiley Periodicals, Inc. J Combin Designs 11: 100–112, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jcd.10040
Structure theorem for tournaments omitting N5
Authors: Latka Brenda J.
Published: February 2003

A finite tournament T is tight if the class of finite tournaments omitting T is well‐quasi‐ordered. We show here that a certain tournament N5 on five vertices is tight. This is one of the main steps in an exact classification of the tight tournaments, as explained in [10]; the third and final step is carried out in [11]. The proof involves an encoding of the indecomposable tournaments omitting N5 by a finite alphabet, followed by an application of Kruskal's Tree Theorem. This problem arises in model theory and in computational complexity in a more general form, which remains open: the problem is to give an effective criterion for a finite set {T1,…,Tk} of finite tournaments to be tight in the sense that the class of all finite tournaments omitting each of T1,…,Tk is well‐quasi‐ordered. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 165–192, 2003
Coloring with three‐colored subgraphs
Authors: Mubayi Dhruv
Published: February 2003

Let f(n) be the minimum number of colors required to color the edges of Kn,n such that every copy of K3,3 receives at least three colors on its edges. We prove that

$$(0.62+o(1))\sqrt{n}< \, f(n)< \, (1+o(1))\sqrt{n}$$,

where the upper bound is obtained by an explicit edge‐coloring. This complements earlier results of Axenovich, Füredi, and Mubayi [1]. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 193–198, 2003
Degree conditions for k‐ordered hamiltonian graphs
Authors: Faudree Ralph J. , Gould Ronald. J. , Kostochka Alexandr V. , Lesniak Linda , Schiermeyer Ingo , Saito Akira
Published: February 2003

For a positive integer k, a graph G is k‐ordered hamiltonian if for every ordered sequence of k vertices there is a hamiltonian cycle that encounters the vertices of the sequence in the given order. It is shown that if G is a graph of order n with 3 ≤ k ≤ n/2, and deg(u) + deg(v) ≥ n + (3k − 9)/2 for every pair u, v of nonadjacent vertices of G, then G is k‐ordered hamiltonian. Minimum degree conditions are also given for k‐ordered hamiltonicity. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 199–210, 2003
Degree sequence conditions for equal edge‐connectivity and minimum degree, depending on the clique number
Authors: Volkmann Lutz
Published: February 2003

Using the well‐known Theorem of Turán, we present in this paper degree sequence conditions for the equality of edge‐connectivity and minimum degree, depending on the clique number of a graph. Different examples will show that these conditions are best possible and independent of all the known results in this area. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 234–245, 2003
Edge list multicoloring trees: An extension of Hall's theorem
Authors: Cropper Mathew , Gyárfás András , Lehel Jenő
Published: February 2003

We prove a necessary and sufficient condition for the existence of edge list multicoloring of trees. The result extends the Halmos–Vaughan generalization of Hall's theorem on the existence of distinct representatives of sets. © 2003 Wiley Periodicals, Inc. J Graph Theory 42: 246–255, 2003
Tumor necrosis factor‐α regulation of insulin‐like growth factor‐I, type 1 IGF receptor, and IGF binding protein expression in cerebellum of transgenic mice
Authors: Ye Ping , Price Wayne , Kassiotis George , Kollias George , D'Ercole A. Joseph
Published: February 2003

Tumor necrosis factor‐α (TNF‐α), a proinflammatory cytokine, has been implicated in the pathogenesis of several disorders and injuries in the central nervous system (CNS). Unlike IGF‐I, which promotes CNS growth, TNF‐α causes brain growth retardation and neural damage. Recently TNF‐α has been shown to inhibit IGF‐I signaling and actions in non‐neural tissue. To investigate whether TNF‐α deleteriously influences brain growth by altering the IGF‐I system in vivo, we examined the expression of IGF‐I, the type 1 IGF receptor (IGF1R) and IGF binding proteins (IGFBPs) in the brain of transgenic (Tg) mice with murine TNF‐α overexpression. We show that overexpression of TNF‐α reduces the weights of whole brain and all brain regions examined during development. In adult TNF‐α Tg mice, cerebellum (CB) exhibited the greatest reduction in weight among the five brain regions examined, being ∼77% of that in wild‐type (WT) mice. IGF‐I abundance was decreased in the CB, as well as in cerebral cortex and diencephalon, of TNF‐α Tg mice. When compared to those in WT mice, CB IGF‐I abundance in Tg mice was reduced by ∼35%, ∼45%, and ∼40% at 2, 6, and 9 weeks of age, respectively. Of the IGFBPs studied the abundance of IGFBP‐3 and IGFBP‐4 was increased by 2–3.7‐fold, and the abundance of IGFBP‐5 was decreased by ∼3‐fold (as judged by Western immunoblot analysis). Histological analysis and immunocytochemical staining confirmed that TNF‐α specifically increases IGFBP‐3 and IGFBP‐4 immunoreactivity, as well as that of the IGF1R, in radial glial and Purkinje cells. In addition, TNF‐α alters CB cytoarchitecture, apparently by influencing granule cell migration. Our data indicate that TNF‐α alters the expression of IGF‐I system proteins in vivo, and suggest that altered expression of IGF‐I system proteins may in part explain TNF‐α deleterious actions on brain growth. © 2002 Wiley‐Liss, Inc.
Organic cation transporter capable of transporting serotonin is up‐regulated in serotonin transporter‐deficient mice
Authors: Schmitt A. , Mössner R. , Gossmann A. , Fischer I.G. , Gorboulev V. , Murphy D.L. , Koepsell H. , Lesch K.P.
Published: February 2003

The serotonin (5HT) transporter (5HTT) regulates serotonergic neurotransmission by mediating the reuptake of 5HT from the synaptic cleft. Although lacking the high affinity and selectivity of the 5HTT, the brain expresses a large number of other transporters, including the polyspecific organic cation transporters (OCTs). OCT1 and OCT3, members of the potential‐sensitive organic cation transporter gene family, physiologically transport a wide spectrum of organic cations. In addition, both transporters mediate low‐affinity 5HT transport and, therefore, may participate in the clearance of excessive 5HT. Because concentrations of extracellular 5HT are increased in the brain of 5HTT‐deficient mice, they are a model for investigating the role of OCTs in 5HT system homeostasis. Here, we analyzed OCT1 and OCT3 gene expression in the brain of 5HTT knockout mice by semiquantitative competitive polymerase chain reaction and in situ hybridization. We demonstrate that, in 5HTT‐deficient mice, OCT3 mRNA concentrations were significantly increased in the hippocampus, but not in other brain regions, including cortex, striatum, cerebellum, and brainstem. In contrast, no difference in OCT1 expression was detected between 5HTT knockout and control mice. Up‐regulation of OCT3 expression and enhanced low‐affinity 5HT uptake may limit the adverse effects of elevated extracellular 5HT and may play a critical role in maintaining 5HT‐dependent functions of the hippocampus in the absence of 5HTT. © 2002 Wiley‐Liss, Inc.
Thyroid hormones regulate the frequency of miniature end‐plate currents in pre‐ and prometamorphic stages of the tadpole tail
Authors: Rojas Legier V. , Bonilla Laurie , Baez Sheila , Lasalde‐Dominicci José A.
Published: February 2003

Thyroid hormones (THs), primarily 3,3′,5‐triiode‐L‐thyronine (T3), have been clearly established as natural inducers of apoptosis during metamorphosis of anuran embryos. We decided to use this phenomenon to test the hypothesis that, prior to genomic activation, T3 has acute actions in the neuromuscular junction (NMJ) of the tail of amphibian embryos. We detected a dramatic increase in the production of miniature end‐plate currents (MEPCs) 2–5 min after continuous application of T3 (250 nM) using focal recordings under voltage clamp. Furthermore, this increase in the spontaneous release of neurotransmitter, evaluated by the MEPC frequency, was maintained for several hours. Reverse‐T3, the “inhibitory” form of THs, prevented this increase in MEPC frequency, suggesting that this is probably a highly specific action of T3. In addition, the elevation in MEPC frequency induced by T3 was unchanged in the presence or absence of extracellular calcium. The T3‐mediated increase in MEPC frequency was blocked by niflumic acid, a nonsteroidal antinflammatory fenamate used to prevent the apoptotic volume decrease observed in many systems. The present study demonstrated that T3 induces a remarkable nongenomic action in the NMJ of the tadpole tail at pre‐ and promatamorphic stages. © 2002 Wiley‐Liss, Inc.
Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8
Authors: Chong Zhao Zhong , Lin Shi‐Hua , Kang Jing‐Qiong , Maiese Kenneth
Published: February 2003

Erythropoietin (EPO) modulates primarily the proliferation of immature erythroid precursors, but little is known of the potential protective mechanisms of EPO in the central nervous system. We therefore examined the ability of EPO to modulate a series of death‐related cellular pathways during anoxia and free radical induced neuronal degeneration. Neuronal injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine exposure, protein kinase B phosphorylation, cysteine protease activity, mitochondrial membrane potential, and mitogen‐activated protein (MAP) kinase phosphorylation. We demonstrate that constitutive neuronal EPO is insufficient to prevent cellular injury, but that signaling through the EPO receptor remains biologically responsive to exogenous EPO administration. Exogenous EPO is both necessary and sufficient to prevent acute genomic DNA destruction and subsequent phagocytosis through membrane PS exposure, because neuronal protection by EPO is completely abolished by co‐treatment with an anti‐EPO neutralizing antibody. Through pathways that involve the initial activation of protein kinase B, EPO maintains mitochondrial membrane potential. Subsequently, EPO inhibits caspase 8‐, caspase 1‐, and caspase 3‐like activities linked to cytochrome c release through mechanisms that are independent from the MAP kinase systems of p38 and JNK. Elucidating some of the novel neuroprotective pathways employed by EPO may further the development of new therapeutic strategies for neurodegenerative disorders. © 2002 Wiley‐Liss, Inc.