bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurements of cloud droplet activation of aerosol particles at a clean subarctic background site
Authors: Komppula Mika , Lihavainen Heikki , Kerminen Veli‐Matti , Kulmala Markku , Viisanen Yrjö
Published: March 2005

Two years of continuous aerosol particle size distribution measurements provided the basis for this cloud droplet activation study. The cloud droplet activation of aerosol particles was studied in Pallas, a clean background site in northern Finland. A slightly different approach compared with traditional methods is presented by measuring simultaneously the cloud interstitial particle size spectrum and a nearby out‐of‐cloud particle size spectrum. The main advantage of this approach is that one can determine the activated fraction of different‐size particles over the whole submicron‐size range and that a large number of cloud activation events can be analyzed. The number of cloud droplet activation days peaked in late autumn and was lowest in summer. The annual variation of “cloud droplet activation” events followed the annual pattern of low clouds (those below 1000 m). A relation was found between the total particle number concentration outside the cloud and the number of activated particles. A larger particle concentration led to a higher number of activated particles, a lower activation percent, and a larger activation diameter (D50). D50 was on average 80 nm and varied from 50 to 128 nm. The average fraction of activated particles during the cloud events was 47% and varied from 9 to 86%. The cleaner and colder air masses from the northern Atlantic or the Arctic Ocean had, on average, 15 nm lower D50 than the more polluted air masses from south and east containing more particles. The annual variation of the number of the activated particles and other variables were also closely related to the annual variation of particle concentration (high in summer and low in winter). On average 87 and 30% of accumulation and Aitken mode particles, respectively, were activated. Aitken mode particles were observed to cover up to 55% of the total number of activated particles (i.e., number of formed droplets), which demonstrates that they have a significant effect on cloud droplet activation and must be taken into account when estimating the aerosol indirect climate effects.
Influence of slightly soluble organics on aerosol activation
Authors: Abdul‐Razzak Hayder , Ghan Steven J.
Published: March 2005

This paper examines the effects of slightly soluble organics on aerosol activation in a parcel of air rising adiabatically. Slightly soluble organics can affect aerosol activation by three mechanisms: lowering surface tension, altering the bulk hygroscopicity, and delaying the growth of particles because of their lower solubilities. The first and second mechanisms have already been addressed in a previous paper. Here we address the third mechanism by simulating the activation process of aerosol particles modeled using a single lognormal size distribution and consisting of an internal uniform chemical mixture of adipic acid (representing slightly soluble organics having extremely low solubility as a worst‐case scenario) and ammonium sulfate. The simulations were carried out using measured solubility of adipic acid spanning a wide range of physical and dynamical parameters. The same conditions were resimulated but assuming fully soluble aerosols. Results of the simulations show that although the low solubility of the adipic acid alters Köhler curves and increases critical supersaturation of the smaller particles (Köhler curves of the larger particles are not affected because these particles are completely dissolved at the initial supersaturation of zero), low solubility has minimal to no effect on the parcel supersaturation except for particles consisting of more than 95% adipic acid. Furthermore, since aerosols in realistic atmospheric conditions do not contain more than 90% organics, we should be only interested in smaller concentrations (less than 90% by mass). Accordingly, we conclude that the slightly soluble organics can be assumed to be fully soluble for the purpose of predicting the fraction of activation and the maximum supersaturation with negligible error and it is not necessary to retune the previously developed parameterization of aerosol activation.
CB1 cannabinoid receptor‐mediated modulation of food intake in mice
Authors: Wiley Jenny L , Burston James J , Leggett Darnica C , Alekseeva Olga O , Razdan Raj K , Mahadevan Anu , Martin Billy R
Published: March 2005

Marijuana's appetite‐increasing effects have long been known. Recent research suggests that the CB1 cannabinoid receptor antagonist SR141716A may suppress appetite. This study represents a further, systematic investigation of the role of CB1 cannabinoid receptors in the pharmacological effects of cannabinoids on food intake.

Mice were food‐restricted for 24 h and then allowed access to their regular rodent chow for 1 h. Whereas the CB1 antagonist SR141716A dose‐dependently decreased food consumption at doses that did not affect motor activity, Δ9‐tetrahydrocannabinol (Δ9‐THC) increased food consumption at doses that had no effect on motor activity. O‐3259 and O‐3257, structural analogs of SR141716A, produced effects similar to those of the parent compound.

Amphetamine (a known anorectic) and diazepam (a benzodiazepine and CNS depressant) decreased food consumption, but only at doses that also increased or decreased motor activity, respectively. The CB2 cannabinoid receptor antagonist SR144528 and the nonpsychoactive cannabinoid cannabidiol did not affect food intake nor activity.

SR141716A decreased feeding in wild‐type mice, but lacked pharmacological activity in CB1 knockout mice; however, basal food intake was lower in CB1 knockout mice. Amphetamine decreased feeding in both mouse genotypes.

These results suggest that SR141716A may affect the actions of endogenous cannabinoids in regulating appetite or that it may have effects of its own aside from antagonism of cannabinoid effects (e.g., decreased feeding behavior and locomotor stimulation). In either case, these results strongly suggest that CB1 receptors may play a role in regulation of feeding behavior.

British Journal of Pharmacology (2005) 145, 293–300. doi:10.1038/sj.bjp.0706157
Emerging roles for cyclooxygenase‐2 in gastrointestinal mucosal defense
Authors: Wallace John L , Devchand Pallavi R
Published: March 2005

The development of selective inhibitors of cyclooxygenase‐2 (COX‐2) was based on the concept that this enzyme played little, if any, role in modulating the ability of the gastrointestinal (GI) tract to resist and respond to injury. There is now overwhelming evidence that this is far from true. Indeed, COX‐2 mediates several of the most important components of ‘mucosal defense’, contributes significantly to the resolution of GI inflammation and plays a crucial role in regulating ulcer healing. COX‐2 also contributes to long‐term changes in GI function after bouts of inflammation.

British Journal of Pharmacology (2005) 145, 275–282. doi:10.1038/sj.bjp.0706201
Megakaryocyte apoptosis: sorting out the signals
Authors: Gordge Michael P
Published: March 2005

British Journal of Pharmacology (2005) 145, 271–273. doi:10.1038/sj.bjp.0706202
A chitosanase from Paecilomyces lilacinus with binding affinity for specific chito‐oligosaccharides
Authors: Chen Yi‐Yun , Cheng Chih‐Yu , Haung Te‐Lin , Li Yaw‐Kuen
Published: March 2005

A purple‐spore, rhizosphere‐inhabiting nematophagous fungus, further identified as Paecilomyces lilacinus, was found to grow on chitosanase‐detecting plate. An induced endochitosanase having a molecular mass of 23 kDa was purified from the culture medium by a single cation‐exchange column‐chromatography step. Its optimum pH, optimum temperature and pI were found to be 6.0, 50 °C and 8.3 respectively. The N‐terminal amino acid sequence of the purified enzyme was partially determined. On the basis of the partial sequence XQLPANLXXIYD and the BLAST results, the purified chitosanase was classified as a new member of the family 75 glycohydrolases. Complete hydrolysis of 95% deacetylated chitosan by the isolated chitosanase released chitotriose, chitotetraose and chitopentaose as the major hydrolytic products. Two oligosaccharides, which were further determined to be GlcN–GlcN–GlcNAc and GlcNAc–GlcN–GlcN–GlcNAc by chemical methylation followed by liquid chromatography–tandem MS analysis, were obtained after the denaturation of the purified chito‐sanase. This is the first documented finding that chitosanase can be produced in a Paecilomyces strain and that it has binding affinity for specific N‐acetylated oligosaccharides.
Applying biotin–streptavidin binding for iscom (immunostimulating complex) association of recombinant immunogens
Authors: Wikman Maria , Friedman Mikaela , Pinitkiatisakul Sunan , Hemphill Andrew , Lövgren‐Bengtsson Karin , Lundén Anna , Ståhl Stefan
Published: March 2005

We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptide or lipid tags to improve their capacity to be incorporated into an adjuvant formulation. In the present study, we have explored the strong interaction between biotin and SA (streptavidin) (KD≈10−15 M) to couple recombinant immunogens to iscoms (immunostimulating complexes). Two different concepts were evaluated. In the first concept, a His6‐tagged SA fusion protein (His6–SA) was bound to Ni2+‐loaded iscom matrix (iscom without associated protein), and biotinylated immunogens were thereafter associated with the SA‐coated iscoms. The immunogens were either biotinylated in vivo on E. coli expression or double biotinylated in vivo and in vitro. In the second concept, the recombinant immunogens were expressed as SA fusion proteins, which were directly bound to a biotinylated iscom matrix. A 53‐amino‐acid malaria peptide (M5), derived from the central repeat region of the Plasmodium falciparum blood‐stage antigen Pf155/RESA, and a 232‐amino‐acid segment (SRS2′) from the central region (from Pro‐97 to Lys‐328) of the major surface antigen NcSRS2 of the protozoan parasite Neospora caninum, served as model immunogens in the present study. All fusion proteins generated were found to be efficiently expressed and could be recovered to high purity using affinity chromatography. The association between the different immunogen‐containing fusion proteins and the corresponding iscom matrix was demonstrated by analytical ultracentrifugation in a sucrose density gradient. However, some fusion proteins were, to a certain extent, also found to associate unspecifically with a regular iscom matrix. Furthermore, selected iscom fractions were demonstrated to induce high‐titre antigen‐specific antibody responses on immunization of mice. For the particular target immunogen SRS2′, the induced antibodies demonstrated reactivity to the native antigen NcSRS2. We believe that the presented concepts offer convenient methods to achieve efficient adjuvant association of recombinant immunogens, and the advantages and disadvantages of the two concepts are discussed.
Rapid characterization of outer‐membrane proteins in Neisseria lactamica by SELDI–TOF‐MS (surface‐enhanced laser desorption ionization–time‐of‐flight MS) for use in a meningococcal vaccine
Authors: Mukhopadhyay Tarit Kumar , Halliwell Denise , O'Dwyer Cliona , Shamlou Parviz Ayazi , Levy Myriam Susana , Allison Nigel , Gorringe Andrew , Reddin Karen M.
Published: March 2005

Immunological and epidemiological evidence suggests that the development of natural immunity to meningococcal disease results from colonization of the nasopharynx by commensal Neisseria species, particularly with Neisseria lactamica. We have reported previously that immunization with N. lactamica outer‐membrane vesicles containing the major OMPs (outer‐membrane proteins) protected mice against lethal challenge with meningococci of diverse serogroups and serotypes and has the potential to form the basis of a vaccine against meningococcal diseases [Oliver, Reddin, Bracegirdle et al. (2002) Infect. Immun. 70, 3621–3626]. In the present study, we have shown that biomass production and the profile of outer‐membrane vesicle proteins may be affected by fermentation conditions and, in particular, media composition. Ciphergen SELDI–TOF Protein Chips® were used as a rapid and sensitive new method in comparison with conventional SDS/PAGE. SELDI–TOF‐MS (surface‐enhanced laser‐desorption ionization–time‐of‐flight MS) reproducibly identified three major OMPs (NspA, RmpM and PorB) and detected the changes in the protein profile when the growth medium was altered. The findings of this work indicate that SELDI–TOF‐MS is a useful tool for the rapid optimization of OMP production in industrial fermentation processes and can be adapted as a Process Analytical Technology (http://www.fda.gov/cder/OPS/PAT.htm).
The cryopreservation of human embryonic stem cells
Authors: Heng Boon Chin , Kuleshova Lilia L. , Bested Soren Müller , Liu Hua , Cao Tong
Published: March 2005

hES (human embryonic stem) cells hold tremendous potential in the newly emerging field of regenerative medicine, in addition to being a useful tool in basic scientific research and for pharmacological and cytotoxicity screening. However, an essential prerequisite for the future widespread application of hES cells are the development of efficient cryopreservation protocols to facilitate their storage and transportation. This review summarizes the current state of progress in the field of hES cell cryopreservation, by critically examining and comparing the various cryopreservation protocols that have been developed. These can be classified into two categories: (1) conventional slow‐cooling protocols and (2) vitrification protocols. Previously, the application of slow‐cooling cryopreservation protocols to freely‐suspended hES cell clumps yielded extremely dismal results. However, a recent study demonstrated that post‐thaw survivability was markedly improved when slow‐cooling protocols were applied instead to adherent hES colonies. Vitrification protocols have been shown to be much better than the standard slow‐cooling protocol for the cryopreservation of freely suspended hES cell clumps. However, no study has yet attempted to apply vitrification protocols to adherent hES colonies. It must be noted that vitrification protocols are extremely labour‐intensive and tedious to perform manually. Additionally, the use of cryostraws in vitrification protocols is unsuited for handling bulk quantities of hES cells, in addition to posing serious technical difficulties in developing machine automation for cryopreservation. These are some of the major challenges that have to be overcome if further progress is to be made in this field.
In search of markers for the stem cells of the corneal epithelium
Authors: Pajoohesh‐Ganji Ahdeah , Stepp Mary Ann
Published: March 2005

The anterior one‐fifth of the human eye is called the cornea. It consists of several specialized cell types that work together to give the cornea its unique optical properties. As a result of its smooth surface and clarity, light entering the cornea focuses on the neural retina allowing images to come into focus in the optical centres of the brain. When the cornea is not smooth or clear, vision is impaired. The surface of the cornea consists of a stratified squamous epithelium that must be continuously renewed. The cells that make up this outer covering come from an adult stem cell population located at the corneal periphery at a site called the corneal limbus. While engaging in the search for surface markers for corneal epithelial stem cells, vision scientists have obtained a better understanding of the healthy ocular surface. In this review, we summarize the current state of knowledge of the ocular surface and its adult stem cells, and analyse data as they now exist regarding putative corneal epithelial stem cell markers.
Distinct signalling particles containing ERK/MEK and B-Raf in PC12 cells
Authors: MacCORMICK Matt , MODERSCHEIM Tanja , van der SALM Louise W. M. , MOORE Anna , PRYOR Shona Clements , McCAFFREY Gretchen , GRIMES Mark L.
Published: March 2005

Although several multiprotein complexes containing MAPKs (mitogen-activated protein kinases) have been identified using overexpression of kinases and scaffold proteins, the components of the complexes and their physical properties at endogenous expression levels have not been defined. We characterized a large protein complex containing a nerve-growth-factor-activated ERK (extracellular-signal-regulated kinase) and MEK (MAPK/ERK kinase) in rat pheochromocytoma (PC12) cells. This protein complex fractionated into a high-speed pellet and was resistant to non-ionic detergent treatments that solubilized membranes. Disruption of protein–protein interactions by treatment with high salt was required to facilitate immunoprecipitation of active ERK1 and co-precipitation of MEK1. Microtubule fragments were also present in the detergent-resistant high-speed pellet, and some kinases were bound to them, especially ERK1b (an alternatively spliced isoform of ERK1), which showed a strong preference for binding microtubules. The large protein complex containing ERK1 and MEK1 was resolved by velocity sedimentation from fragments of microtubules; however, it did not contain other scaffolding components known to bind ERK and MEK. B-Raf was also present in a distinct detergent-resistant, microtubule-independent protein complex slightly larger than that containing ERK and MEK. We conclude that there are two independent nerve growth factor-regulated ‘signalling particles’ with an estimated size of 60–75 S, one containing ERK1 and MEK1 and the other containing B-Raf. These signalling particles may have a role in the temporal and spatial regulation of kinase activity inside cells.
Is the regulation of galactose 1-phosphate tuned against gene expression noise?
Authors: de ATAURI Pedro , ORRELL David , RAMSEY Stephen , BOLOURI Hamid
Published: March 2005

The average number of mRNA molecules per active gene in yeast can be remarkably low. Consequently, the relative number of copies of each transcript per cell can vary greatly from moment to moment. When these transcripts are encoding metabolic enzymes, how do the resulting variations in enzyme concentrations affect the regulation of metabolic intermediates? Using a kinetic model of galactose utilization in yeast, we analysed the transmission of noise from transcription and translation on metabolic intermediate regulation. In particular, the effect of the kinetic properties of the galactose-1-phosphate uridylyltransferase reaction on the transmission of noise was analysed.
Identification and characterization of Sulfolobus solfataricus
D-gluconate dehydratase: a key enzyme in the non-phosphorylated Entner–Doudoroff pathway
Authors: KIM Seonghun , LEE Sun Bok
Published: March 2005

The extremely thermoacidophilic archaeon Sulfolobus solfataricus utilizes D-glucose as a sole carbon and energy source through the non-phosphorylated Entner–Doudoroff pathway. It has been suggested that this micro-organism metabolizes D-gluconate, the oxidized form of D-glucose, to pyruvate and D-glyceraldehyde by using two unique enzymes, D-gluconate dehydratase and 2-keto-3-deoxy-D-gluconate aldolase. In the present study, we report the purification and characterization of D-gluconate dehydratase from S. solfataricus, which catalyses the conversion of D-gluconate into 2-keto-3-deoxy-D-gluconate. D-Gluconate dehydratase was purified 400-fold from extracts of S. solfataricus by ammonium sulphate fractionation and chromatography on DEAE-Sepharose, Q-Sepharose, phenyl-Sepharose and Mono Q. The native protein showed a molecular mass of 350 kDa by gel filtration, whereas SDS/PAGE analysis provided a molecular mass of 44 kDa, indicating that D-gluconate dehydratase is an octameric protein. The enzyme showed maximal activity at temperatures between 80 and 90 °C and pH values between 6.5 and 7.5, and a half-life of 40 min at 100 °C. Bivalent metal ions such as Co2+, Mg2+, Mn2+ and Ni2+ activated, whereas EDTA inhibited the enzyme. A metal analysis of the purified protein revealed the presence of one Co2+ ion per enzyme monomer. Of the 22 aldonic acids tested, only D-gluconate served as a substrate, with Km=0.45 mM and Vmax=0.15 unit/mg of enzyme. From N-terminal sequences of the purified enzyme, it was found that the gene product of SSO3198 in the S. solfataricus genome database corresponded to D-gluconate dehydratase (gnaD). We also found that the D-gluconate dehydratase of S. solfataricus is a phosphoprotein and that its catalytic activity is regulated by a phosphorylation–dephosphorylation mechanism. This is the first report on biochemical and genetic characterization of D-gluconate dehydratase involved in the non-phosphorylated Entner–Doudoroff pathway.
Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting
Authors: YORIKAWA Chiharu , SHIBATA Hideki , WAGURI Satoshi , HATTA Kazumi , HORII Mio , KATOH Keiichi , KOBAYASHI Toshihide , UCHIYAMA Yasuo , MAKI Masatoshi
Published: March 2005

CHMP6 (charged multivesicular body protein 6) is a human orthologue of yeast Vps (vacuolar protein sorting) 20, a component of ESCRT (endosomal sorting complex required for transport)-III. Various CHMP6 orthologues in organisms ranging from yeast to humans contain the N-myristoylation consensus sequence at each N-terminus. Metabolic labelling of HEK-293 (human embryonic kidney) cells showed the incorporation of [3H]myristate into CHMP6 fused C-terminally to GFP (green fluorescent protein) (CHMP6–GFP). Interactions of CHMP6 with another ESCRT-III component CHMP4b/Shax [Snf7 (sucrose non-fermenting 7) homologue associated with Alix] 1, one of three paralogues of human Vps32/Snf7, and with EAP20 (ELL-associated protein 20), a human counterpart of yeast Vps25 and component of ESCRT-II, were observed by co-immunoprecipitation of epitope-tagged proteins expressed in HEK-293 cells. The in vitro pull-down assays using their recombinant proteins purified from Escherichia coli demonstrated direct physical interactions which were mediated by the N-terminal basic half of CHMP6. Overexpressed CHMP6-GFP in HeLa cells exhibited a punctate distribution throughout the cytoplasm especially in the perinuclear area, as revealed by fluorescence microscopic analysis. Accumulation of LBPA (lysobisphosphatidic acid), a major phospholipid in internal vesicles of an MVB (multivesicular body), was observed in the CHMP6–GFP-localizing area. FLAG-tagged EAP20 distributed diffusely, but exhibited a punctate distribution on co-expression with CHMP6–GFP. Overexpression of CHMP6–GFP caused reduction of transferrin receptors on the plasma membrane surface, but caused their accumulation in the cytoplasm. Ubiquitinated proteins and endocytosed EGF continuously accumulated in CHMP6–GFP-expressing cells. These results suggest that CHMP6 acts as an acceptor for ESCRT-II on endosomal membranes and regulates cargo sorting.
Expression of secretory phospholipase A2 enzymes in lungs of humans with pneumonia and their potential prostaglandin-synthetic function in human lung-derived cells
Authors: MASUDA Seiko , MURAKAMI Makoto , MITSUISHI Michiko , KOMIYAMA Kazuo , ISHIKAWA Yukio , ISHII Toshiharu , KUDO Ichiro
Published: March 2005

Although a number of sPLA2 (secretory phospholipase A2) enzymes have been identified in mammals, the localization and functions of individual enzymes in human pathologic tissues still remain obscure. In the present study, we have examined the expression and function of sPLA2s in human lung-derived cells and in human lungs with pneumonia. Group IID, V and X sPLA2s were expressed in cultured human bronchial epithelial cells (BEAS-2B) and normal human pulmonary fibroblasts with distinct requirement for cytokines (interleukin-1β, tumour necrosis factor α and interferon-γ). Lentivirus- or adenovirus-mediated transfection of various sPLA2s into BEAS-2B or normal human pulmonary fibroblast cells revealed that group V and X sPLA2s increased arachidonate release and prostaglandin production in both cell types, whereas group IIA and IID sPLA2s failed to do so. Immunohistochemistry of human lungs with pneumonia demonstrated that group V and X sPLA2s were widely expressed in the airway epithelium, interstitium and alveolar macrophages, in which group IID sPLA2 was also positive, whereas group IIA sPLA2 was restricted to the pulmonary arterial smooth muscle layers and bronchial chondrocytes, and group IIE and IIF sPLA2s were minimally detected. These results suggest that group V and X sPLA2s affect lung pathogenesis by facilitating arachidonate metabolism or possibly through other functions.
Functional dichotomy of A20 in apoptotic and necrotic cell death
Authors: STORZ Peter , DÖPPLER Heike , FERRAN Christiane , GREY Shane T. , TOKER Alex
Published: March 2005

ROS (reactive oxygen species) play important roles in the progression of a number of human pathologies. ROS promote cell death, but can also induce gene transcription. The transcription factor NF-κB (nuclear factor κB) plays a critical role in oxidative stress responses. One of the proteins regulated by NF-κB is the zinc-finger protein A20. In TNF (tumour necrosis factor)-α signalling, NF-κB induction of A20 leads to increased cell survival. In the present paper, we show that in response to oxidative stress, A20 actually enhances cell death by necrosis, but not by apoptosis. Exposure of cells to ROS leads to the up-regulation of A20 which acts via a negative-feedback loop to block NF-κB activation and cellular survival. Silencing of A20 by RNAi (RNA interference) increases both the induction of NF-κB and the subsequent survival of cells exposed to high doses of oxidative stress, which, in untreated cells, promotes death by necrosis. Cells which express high basal levels of A20 are less protected from oxidative-stress-induced cell death when compared with cells with lower A20 expression. We also show that A20 regulates NF-κB by blocking the degradation of IκB (inhibitory protein κB) α. These data highlight a novel role for A20 in oxidative stress responses by terminating NF-κB-dependent survival signalling and thus sensitizing cells to death by necrosis.
ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7
Authors: BRIDGES Lance C. , SHEPPARD Dean , BOWDITCH Ron D.
Published: March 2005

The ADAM (adisintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion.
Characterization of carnitine and fatty acid metabolism in the long-chain acyl-CoA dehydrogenase-deficient mouse
Authors: van VLIES Naomi , TIAN Liqun , OVERMARS Henk , BOOTSMA Albert H. , KULIK Willem , WANDERS Ronald J. A. , WOOD Philip A. , VAZ Frédéric M.
Published: March 2005

In the present paper, we describe a novel method which enables the analysis of tissue acylcarnitines and carnitine biosynthesis intermediates in the same sample. This method was used to investigate the carnitine and fatty acid metabolism in wild-type and LCAD−/− (long-chain acyl-CoA dehydrogenase-deficient) mice. In agreement with previous results in plasma and bile, we found accumulation of the characteristic C14:1-acylcarnitine in all investigated tissues from LCAD−/− mice. Surprisingly, quantitatively relevant levels of 3-hydroxyacylcarnitines were found to be present in heart, muscle and brain in wild-type mice, suggesting that, in these tissues, long-chain 3-hydroxyacyl-CoA dehydrogenase is rate-limiting for mitochondrial β-oxidation. The 3-hydroxyacylcarnitines were absent in LCAD−/− tissues, indicating that, in this situation, the β-oxidation flux is limited by the LCAD deficiency. A profound deficiency of acetylcarnitine was observed in LCAD−/− hearts, which most likely corresponds with low cardiac levels of acetyl-CoA. Since there was no carnitine deficiency and only a marginal elevation of potentially cardiotoxic acylcarnitines, we conclude from these data that the cardiomyopathy in the LCAD−/− mouse is caused primarily by a severe energy deficiency in the heart, stressing the important role of LCAD in cardiac fatty acid metabolism in the mouse.
Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders
Authors: GORRELL Mark D.
Published: March 2005

DP (dipeptidyl peptidase) IV is the archetypal member of its six-member gene family. Four members of this family, DPIV, FAP (fibroblast activation protein), DP8 and DP9, have a rare substrate specificity, hydrolysis of a prolyl bond two residues from the N-terminus. The ubiquitous DPIV glycoprotein has proved interesting in the fields of immunology, endocrinology, haematology and endothelial cell and cancer biology and DPIV has become a novel target for Type II diabetes therapy. The crystal structure shows that the soluble form of DPIV comprises two domains, an α/β-hydrolase domain and an eight-blade β-propeller domain. The propeller domain contains the ADA (adenosine deaminase) binding site, a dimerization site, antibody epitopes and two openings for substrate access to the internal active site. FAP is structurally very similar to DPIV, but FAP protein expression is largely confined to diseased and damaged tissue, notably the tissue remodelling interface in chronically injured liver. DPIV has a variety of peptide substrates, the best studied being GLP-1 (glucagon-like peptide-1), NPY (neuropeptide Y) and CXCL12. The DPIV family has roles in bone marrow mobilization. The functional interactions of DPIV and FAP with extracellular matrix confer roles for these proteins in cancer biology. DP8 and DP9 are widely distributed and indirectly implicated in immune function. The DPL (DP-like) glycoproteins that lack peptidase activity, DPL1 and DPL2, are brain-expressed potassium channel modulators. Thus the six members of the DPIV gene family exhibit diverse biological roles.
Signal transduction in prostate cancer progression
Authors: GIOELI Daniel
Published: March 2005

Prostate cancer is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths in the United States. When prostate cancer initially presents in the clinic, the tumour is dependent on androgen for growth and, therefore, responsive to the surgical or pharmacological ablation of circulating androgens. However, there is a high rate of treatment failure because the disease often recurs as androgen-independent metastases. Surprisingly, this late-stage androgen-independent prostate cancer almost always retains expression of the AR (androgen receptor), despite the near absence of circulating androgens. Although late-stage prostate cancer is androgen-independent, the AR still seems to play a role in cancer cell growth at this stage of disease. Therefore a key to understanding hormone-independent prostate cancer is to determine the mechanism(s) by which the AR can function even in the absence of physiological levels of circulating androgen. This review will focus on the role of growth factor signalling in prostate cancer progression to androgen independence and thus outline potential molecular areas of intervention to treat prostate cancer progression.
Therapeutic potential of transdifferentiated cells
Authors: BURKE Zoë D. , TOSH David
Published: March 2005

Cell therapy means treating diseases with the body's own cells. The ability to produce differentiated cell types at will offers a compelling new approach to cell therapy and therefore for the treatment and cure of a plethora of clinical conditions, including diabetes, Parkinson's disease and cardiovascular disease. Until recently, it was thought that differentiated cells could only be produced from embryonic or adult stem cells. Although the results from stem cell studies have been encouraging, perhaps the most startling findings have been the recent observations that differentiated cell types can transdifferentiate (or convert) into a completely different phenotype. Harnessing transdifferentiated cells as a therapeutic modality will complement the use of embryonic and adult stem cells in the treatment of degenerative disorders. In this review, we will examine some examples of transdifferentiation, describe the theoretical and practical issues involved in transdifferentiation research and comment on the long-term therapeutic possibilities.
Dynamic and static photoresponse of ultraviolet-detecting thin-film transistors based on transparent NiOx electrodes and an n-ZnO channel
Authors: Bae H. S. , Choi C. M. , Kim Jae Hoon , Im Seongil
Published: March 2005

We report on the fabrication of an ultraviolet (UV)-detecting thin-film transistor (TFT) using NiOx as source∕drain electrodes and n-ZnO as its channel layer deposited on a SiO2∕p-Si substrate. Rapid thermal annealing of the TFT was carried out in an O2 ambient at 350°C for 1min to increase the transparency of NiOx. In an accumulation mode with a gate bias of 40V, a drain current of only 2μA was obtained in the dark. However, under an illumination of UV light with wavelength 325nm, the drain current dramatically increased up to 13μA. Under UV photons with wavelength 254nm or energy of 4.9eV, much higher than 4.1eV, the energy gap of NiOx, the photocurrent slightly decreased to ∼10μA due to the absorption by NiOx. These photoelectric effects were more pronounced under a gate-bias condition for a depletion (off) mode. The UV-dynamic behavior of our TFTs was also investigated, yielding the UV response time of ∼300ms and UV-on∕off ratio of about 10.
Moderately and strongly supercooled liquids: A temperature-derivative study of the primary relaxation time scale
Authors: Kokshenev Valery B. , Borges Pablo D. , Sullivan Neil S.
Published: March 2005

The primary relaxation time scale τ(T) derived from the glass forming supercooled liquids (SCLs) is discussed within ergodic-cluster Gaussian statistics, theoretically justified near and above the glass-transformation temperature Tg. An analysis is given for the temperature-derivative data by Stickel et al. on the steepness and the curvature of τ(T). Near the mode-coupling-theory (MCT) crossover Tc, these derivatives separate by a kink and a jump, respectively, the moderately and strongly SCL states. After accounting for the kink and the jump, the steepness remains a piecewise conitnuous function, a material-independent equation for the three fundamental characteristic temperatures, Tg, Tc, and the Vogel–Fulcher–Tamman (VFT) T0, is found. Both states are described within the heterostructured model of solidlike clusters parametrized in a self-consistent manner by a minimum set of observable parameters: the fragility index, the MCT slowing-down exponent, and the chemical excess potential of Adam and Gibbs model (AGM). Below the Arrhenius temperature, the dynamically and thermodynamically stabilized clusters emerge with a size of around of seven to nine and two to three molecules above and close to Tg and Tc, respectively. On cooling, the main transformation of the moderately into the strongly supercooled state is due to rebuilding of the cluster structure, and is attributed to its rigidity, introduced through the cluster compressibility. It is shown that the validity of the dynamic AGM (dynamically equivalent to the standard VFT form) is limited by the strongly supercooled state (Tg<T<Tc) where the superrigid cooperative rearranging regions are shown to be well-chosen parametrized solidlike clusters. Extension of the basic parameter set by the observable kinetic and diffusive exponents results in prediction of a subdiffusion relaxation regime in SCLs that is distinct from that established for amorphous polymers.
Conditional expectations associated with quantum states
Authors: Niestegge Gerd
Published: March 2005

An extension of the conditional expectations (those under a given subalgebra of events and not the simple ones under a single event) from the classical to the quantum case is presented. In the classical case, the conditional expectations always exist; in the quantum case, however, they exist only if a certain weak compatibility criterion is satisfied. This compatibility criterion was introduced among others in a recent paper by the author. Then, state-independent conditional expectations and quantum Markov processes are studied. A classical Markov process is a probability measure, together with a system of random variables, satisfying the Markov property and can equivalently be described by a system of Markovian kernels (often forming a semigroup). This equivalence is partly extended to quantum probabilities. It is shown that a dynamical (semi)group can be derived from a given system of quantum observables satisfying the Markov property, and the group generators are studied. The results are presented in the framework of Jordan operator algebras, and a very general type of observables (including the usual real-valued observables or self-adjoint operators) is considered.
Simulation of conformational transitions by the restricted perturbation–targeted molecular dynamics method
Authors: van der Vaart Arjan , Karplus Martin
Published: March 2005

A method for the simulation of conformational transitions is presented. The method, based on targeted molecular dynamics (TMD), limits the conformational change at each molecular dynamics step to a fixed size, that minimizes the root mean square deviation from the target. The method is more efficient than standard TMD and yields lower energy pathways, but, like the TMD method, requires only a single molecular dynamics simulation. Test calculations and comparisons with standard TMD calculations for the alanine dipeptide with the analytic continuum electrostatics implicit solvent model are presented.
A rigorous proof of the Landauer–Büttiker formula
Authors: Cornean Horia D. , Jensen Arne , Moldoveanu Valeriu
Published: March 2005

Recently, Avron et al. in a series of papers shed new light on the question of quantum transport in mesoscopic samples coupled to particle reservoirs by semi-infinite leads. They rigorously treat the case, when the sample undergoes an adiabatic evolution thus generating a current through the leads, and prove the so-called BPT formula. Using a discrete model, we complement their work by giving a rigorous proof of the Landauer–Büttiker formula, which deals with the current generated by an adiabatic evolution on the leads. As is well known from physics, both of these formulas link the conductance coefficients for such systems to the S-matrix of the associated scattering problem. As an application, we discuss resonant transport through a quantum dot. The single charge tunneling processes are mediated by extended edge states, simultaneously localized near several leads.
Laser interactions with embedded Ca metal nanoparticles in single crystal CaF2
Authors: Cramer L. P. , Schubert B. E. , Petite P. S. , Langford S. C. , Dickinson J. T.
Published: March 2005

Single crystal calcium fluoride (CaF2) is an important material for vacuum-ultraviolet optics. Nevertheless, prolonged exposure to energetic radiation can color the material by producing calcium metal nanoparticles. We compare the effectiveness of laser conditioning treatments at wavelengths ranging from the near infrared to the deep ultraviolet in removing this coloration. Treatments at 157, 532, and 1064 nm can significantly reduce the visible coloration due to nanoparticles. In contrast, irradiation at 248 nm has little effect at fluences below the damage threshold for the material employed in this work. We present evidence that the effect of laser irradiation on coloration is principally thermal and is largely confined to the first 50 ns after each laser pulse. We attribute the wavelength dependence of the bleaching process to the wavelength dependence associated with Mie absorption by metal nanoparticles. The consequences of these observations with regard to laser conditioning processes in bulk optical materials are discussed.
Wave interference and band gap control in multiconductor one-dimensional Bragg structures
Authors: Konoplev I. V. , McGrane P. , Cross A. W. , Ronald K. , Phelps A. D. R.
Published: March 2005

A theoretical study of scattering and interference of waves in one-dimensional (1D) Bragg structures, also known as photonic band-gap (PBG) structures, based on multiconductor waveguides is presented. The case of small perturbations of the waveguide walls was analyzed. Using the coupled-wave theory the expression for the wave-coupling coefficient was generalized. The possibility of controlling the scattered wave polarization and the band gap locations in such structures due to the constructive and destructive interference of the waves was demonstrated. It was shown that such control can be achieved by adjusting the relative phase of the 1D periodic perturbations with respect to each other. As an example a 1D structure based on a coaxial waveguide was studied using three-dimensional computer simulations and coupled-wave theory. The dispersion diagrams are presented and the dependence of the reflected wave structure on the phase between the corrugations analyzed and discussed. To demonstrate the validity of the theory the results obtained for the basic coaxial model with a single corrugated conductor are compared with the experimental results observed.
Composition modulation in GaInNAs quantum wells: Comparison of experiment and theory
Authors: Herrera M. , González D. , Hopkinson M. , Gutiérrez M. , Navaretti P. , Liu H. Y. , García R.
Published: March 2005

Composition modulation observed in GaInNAs quantum wells imposes an important handicap to their potential application within optical components, particularly as the indium and nitrogen contents are increased to reach longer wavelengths. In this paper, we compare our experimental results of phase separation in GaInNAs quantum wells grown at different temperatures with recent theoretical models of spinodal decomposition from the literature. This comparison has shown that the regular solution approximation, which explains the higher composition modulation compared to GaInAs samples, provides a more appropriate explanation of GaInNAs decomposition than the usual delta lattice-parameter approximation. Transmission electron microscopy shows no composition modulation contrasts with the chemical sensitive 002 dark field reflection and a strong increase in the intensity of the strain contrasts observed with 220 bright field reflection as the growth temperature increases from 360to460°C. These observations can be explained by an uncoupling between N and In composition profiles forming separate In-rich and N-rich regions according to the regular solution approximation model. We therefore believe that the compositional fluctuations in GaInNAs are not only due to GaInAs decomposition, but that an uncoupled modulation of the III and V elements is also present.
Engineering of boron-induced dislocation loops for efficient room-temperature silicon light-emitting diodes
Authors: Milosavljević M. , Shao G. , Lourenco M. A. , Gwilliam R. M. , Homewood K. P.
Published: March 2005

We have studied the role of boron ion energy in the engineering of dislocation loops for silicon light-emitting diodes (LEDs). Boron ions from 10to80keV were implanted in (100) Si at ambient temperature, to a constant fluence of 1×1015ions∕cm2. After irradiation the samples were annealed for 20min at 950°C by rapid thermal annealing. The samples were analyzed by transmission electron microscopy and Rutherford backscattering spectroscopy. It was found that the applied ion implantation∕thermal processing induces interstitial perfect and faulted dislocation loops in {111} habit planes, with Burgers vectors a∕2⟨110⟩ and a∕3⟨111⟩, respectively. The loops are located around the projected ion range, but stretch in depth approximately to the end of range. Their size and distribution depend strongly on the applied ion energy. In the 10keV boron-implanted samples the loops are shallow, with a mean size of ∼30nm for faulted loops and ∼75nm for perfect loops. Higher energies yield buried, large, and irregularly shaped perfect loops, up to ∼500nm, coexisting with much smaller faulted loops. In the latter case much more Si interstitials are bounded by the loops, which are assigned to a higher supersaturation of interstitials in as-implanted samples, due to separated Frenkel pairs. An interesting phenomenon was found: the perfect loops achieved a steady-state maximum size when the ion energy reached 40keV. Further increase of the ion energy only increased the number of these large loops and made them bury deeper in the substrate. The results of this work contribute to laying a solid ground in controlling the size and distribution of dislocation loops in the fabrication of silicon LEDs.
Bragg magneto-optical Kerr effect measurements at Co stripe arrays on Fe(001)
Authors: Westphalen Andreas , Schmitte Till , Westerholt Kurt , Zabel Hartmut
Published: March 2005

We report on magneto-optical Kerr effect (MOKE) measurements of a patterned spin valve system, consisting of few-micrometers-wide Co stripes on a continuous Fe film separated by a 14-nm-thick Cr spacer layer. The spin valve array was studied by regular longitudinal MOKE in specular geometry as well as in Bragg MOKE geometry, using the diffraction spots from the grating for hysteresis measurements. We have investigated the shape of the hysteresis loops and the Kerr amplitude as a function of the diffraction order and for various grating periods. The hysteresis loops measured at the diffracted spots reveal an amplification of the Kerr signal in the field regime where the magnetization of the Fe and Co layers is antiparallel.
Excitation of the shear horizontal mode in a monolayer by inelastic helium atom scattering
Authors: Bruch L. W. , Hansen F. Y.
Published: March 2005

Inelastic scattering of a low-energy atomic helium beam (HAS) by a physisorbed monolayer is treated in the one-phonon approximation using a time-dependent wave packet formulation. The calculations show that modes with shear horizontal polarization can be excited near high symmetry azimuths of the monolayer, in agreement with recent experiments. The parameters of the calculations are chosen to match the conditions of HAS experiments for triangular incommensurate monolayer solids of xenon, krypton, and argon adsorbed on the (111) face of platinum, and the results show many of the systematic experimental trends for relative excitation probability of the shear horizontal and longitudinal acoustic phonon branches. The inelastic scattering at beam energies near 8 meV is exceedingly sensitive to small misalignment between the scattering plane and the high symmetry directions of the monolayer solid. The diffraction and inelastic processes arise from a strong coupling of the incident atom to the target and the calculated results show large departures from expectations based on analogies to inelastic thermal neutron scattering.